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Sample records for atherosclerosis molecular imaging

  1. Molecular imaging in atherosclerosis

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    Glaudemans, Andor W.J.M.; Slart, Riemer H.J.A. [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Bozzao, Alessandro [Dept. of Neuroradiology, Univ. Rome (Italy); Bonanno, Elena [Univ. Tor Vergata, Rome (Italy). Dept. of Biopathologoy and Diagnostic Imaging; Arca, Marcello [Univ. Rome (Italy). 1. Faculty of Medicine; Dierckx, Rudi A.J.O. [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Ghent Univ. (Belgium); Signore, Alberto [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Univ. Rome (Italy). 2. Faculty of Medicine; Univ. of Rome (Italy). Medicina Nucleare Ospedale

    2010-12-15

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  2. Molecular imaging in atherosclerosis

    Science.gov (United States)

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A. J. O.

    2010-01-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  3. Atherosclerosis (image)

    Science.gov (United States)

    Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

  4. Molecular imaging of atherosclerosis with nanoparticle-based fluorinated MRI contrast agents.

    Science.gov (United States)

    Palekar, Rohun U; Jallouk, Andrew P; Lanza, Gregory M; Pan, Hua; Wickline, Samuel A

    2015-01-01

    As atherosclerosis remains one of the most prevalent causes of patient mortality, the ability to diagnose early signs of plaque rupture and thrombosis represents a significant clinical need. With recent advances in nanotechnology, it is now possible to image specific molecular processes noninvasively with MRI, using various types of nanoparticles as contrast agents. In the context of cardiovascular disease, it is possible to specifically deliver contrast agents to an epitope of interest for detecting vascular inflammatory processes, which serve as predecessors to atherosclerotic plaque development. Herein, we review various applications of nanotechnology in detecting atherosclerosis using MRI, with an emphasis on perfluorocarbon nanoparticles and fluorine imaging, along with theranostic prospects of nanotechnology in cardiovascular disease.

  5. MRI-guided fiber-based fluorescence molecular tomography for preclinical atherosclerosis imaging

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    Li, Baoqiang; Pouliot, Philippe; Lesage, Frederic

    2014-09-01

    Multi-modal imaging combining fluorescent molecular tomography (FMT) with MRI could provide information in these two modalities as well as optimize the recovery of functional information with MR-guidance. Here, we present a MRI-guided FMT system. An optical probe was designed consisting of a fiber plate on the top and bottom sides of the animal bed, respectively. In experiment, animal was installed between the two plates. Mounting fibers on each plate, transmission measuring could be conducted from both sides of the animal. Moreover, an accurate fluorescence reconstruction was achieved with MRI-derived anatomical guidance. The sensitivity of the FMT system was evaluated with a phantom showing that with long fibers, it was sufficient to detect 10nM Cy5.5 solution with ~28.5 dB in the phantom. The system was eventually used to image MMP activity involved in atherosclerosis with two ATX mice and two control mice. The reconstruction results were in agreement with ex vivo measurement.

  6. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

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    Foss, Catherine A., E-mail: cfoss1@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Bedja, Djahida [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Faculty of Medicine and Health Sciences, Macquarie University, Sydney (Australia); Mease, Ronnie C.; Wang, Haofan [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Kass, David A. [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Chatterjee, Subroto [Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Pomper, Martin G. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)

    2015-05-22

    Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

  7. CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

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    Rosemeire A. Silva

    2016-08-01

    Full Text Available The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr−/− mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05, when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr−/− mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC was synthesized and labeled with 111InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC, to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.

  8. Characterization of partial ligation-induced carotid atherosclerosis model using dual-modality molecular imaging in ApoE knock-out mice.

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    Ik Jae Shin

    Full Text Available BACKGROUND: Recently, partial ligation of the common carotid artery (CCA was reported to induce carotid atheromata rapidly in apolipoprotein-E knockout (ApoE(-/- mice. We investigated this new atherosclerosis model by using combined matrix-metalloproteinase (MMP near-infrared fluorescent (NIRF imaging and macrophage-tracking luciferase imaging. METHODOLOGY AND PRINCIPAL FINDINGS: Partial ligation of the left CCA was performed in 10-week-old ApoE(-/- mice on a high fat diet (n=33; the internal and external carotid arteries and occipital artery were ligated, while the superior thyroid artery was left intact. Two thirds of the animals were treated with either LiCl or atorvastatin. At 1-week, Raw264.7 macrophages modified to express the enhanced firefly-luciferase reporter gene (10(7 Raw-luc cells were injected intravenously. At 2-week, NIRF molecular imaging visualized strong MMP-2/9 activity in the ligated area of the left CCA as well as in the aortic arch. Left-to-right ratios of the NIRF signal intensities in the CCA had a decreasing gradient from the highest value in the upper-most ligated area to the lowest value in the lower-most region adjacent to the aortic arch. Luciferase imaging showed that most Raw-luc macrophages were recruited to the ligated area of the CCA rather than to the aortic arch, despite similarly strong MMP-2/9-related NIRF signal intensities in both areas. In addition, LiCl or atorvastatin could reduce MMP-2/9 activity in the aortic arch but not in the ligated area of the CCA. CONCLUSIONS/SIGNIFICANCE: This is the first molecular imaging study to characterize the partial ligation-induced carotid atherosclerosis model. Molecularly divergent types of atherosclerosis were identified: conventional lipogenic atherosclerosis in the aorta vs. flow-related mechanical atherosclerosis in the partially ligated left system.

  9. (18)F-FDG PET imaging of murine atherosclerosis

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    Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina

    2012-01-01

    To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

  10. Hybrid FMT-MRI applied to in vivo atherosclerosis imaging.

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    Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rhéaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

    2014-05-01

    Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice.

  11. Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

    2013-01-01

    Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

  12. Molecular genetics and gene expression in atherosclerosis.

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    Doevendans, P A; Jukema, W; Spiering, W; Defesche, J C; Kastelein, J J

    2001-01-01

    Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically and irrevocably. Molecular cardiology has many different aspects. In this paper the importance of molecular cardiology and genetics for every day clinical practice are briefly outlined. It is expected that in the genetic predisposition for atherosclerotic disease multiple genes are involved (genetics). The role of only a minority of genes involved in the atherosclerotic process is known. Far less is known about particular gene-gene and gene-environment interactions. In some families disease can be explained mostly by a single, major gene (monogenic), of which the lipid disorder Familial Hypercholesterolemia is an example. In other cases, one or several variations in minor genes (multigenic) contribute to an atherosclerotic predisposition, for instance the lipoprotein lipase gene. Although mutations in this gene influence lipoprotein levels, disease development is predominantly depending on environmental influences. Recently several additional genetic risk factors were identified including elevated levels of lipoprotein (a) [Lp(a)], the DD genotype of angiotensin converting enzyme (ACE), and elevated levels of homocysteine. This illustrates the complexity of genetics in relation to atherosclerosis and the difficulty to assign predictive values to separate genetic risk factors. Furthermore, little attention has been given to protective genes thus far, explaining why some high risk patients are protected from vascular disease. Genetics based treatment or elimination of the genetic risk factor requires complete understanding of the pathogenic molecular basis. Once this requirement is fulfilled, disease management can be strived for, provided that adequate medical management

  13. Superparamagnetic Nanoparticles for Atherosclerosis Imaging

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    Fernando Herranz

    2014-06-01

    Full Text Available The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound.

  14. Superparamagnetic Nanoparticles for Atherosclerosis Imaging

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    Herranz, Fernando; Salinas, Beatriz; Groult, Hugo; Pellico, Juan; Lechuga-Vieco, Ana V.; Bhavesh, Riju; Ruiz-Cabello, J.

    2014-01-01

    The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound. PMID:28344230

  15. Quantum dot mediated imaging of atherosclerosis

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    Jayagopal, Ashwath; Haselton, Frederick R [Department of Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Su Yanru; Blakemore, John L; Linton, MacRae F; Fazio, Sergio [Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)], E-mail: rick.haselton@vanderbilt.edu

    2009-04-22

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE{sup -/-} mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  16. Quantum dot mediated imaging of atherosclerosis

    Science.gov (United States)

    Jayagopal, Ashwath; Su, Yan Ru; Blakemore, John L.; Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

    2009-04-01

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE-/- mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  17. PET/MR imaging of atherosclerosis: initial experience and outlook.

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    Rischpler, Christoph; Nekolla, Stephan G; Beer, Ambros J

    2013-01-01

    Hybrid scanners such as PET/CT have in the past emerged as a valuable modality in clinical routine as well as an important research tool. Recently, the newly developed fully integrated PET/MR scanners were introduced to the market, raising high expectations especially due to the excellent soft tissue contrast and functional imaging capabilities of MRI. In this issue of the American Journal of Nuclear Medicine and Molecular Imaging, initial experiences using a hybrid PET/MR scanner for carotid artery imaging in a group of patients with increased risk for atherosclerosis are described. This represents a proof-of-principle study, which could stimulate future applications of this powerful modality in atherosclerotic plaque imaging.

  18. Atherosclerosis

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    Atherosclerosis is a disease in which plaque builds up inside your arteries. Plaque is a sticky substance ... flow of oxygen-rich blood to your body. Atherosclerosis can lead to serious problems, including Coronary artery ...

  19. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

    2015-01-01

    diet (r(2)=0.33, Pinflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients...... with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta. CONCLUSIONS: (18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis....

  20. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

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    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  1. Cellular Imaging of Inflammation in Atherosclerosis Using Magnetofluorescent Nanomaterials

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    Farouc A. Jaffer

    2006-04-01

    Full Text Available Objective: Magnetofluorescent nanoparticles (MFNPs offer the ability to image cellular inflammation in vivo. To better understand their cellular targeting and imaging capabilities in atherosclerosis, we investigated prototypical dextran-coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E−/− mouse model. Methods and Results: In vitro MFNP uptake was highest in activated murine macrophages (p < .001. Apo E−/− mice (n = 11 were next injected with the MFNP (15 mg/kg iron or saline. In vivo magnetic resonance imaging (MRI demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline, which was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging. On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma and colocalized with immunofluorescent macrophages over endothelial cells and smooth muscle cells (p < .001. Conclusions: Here we show that (1 the in vitro and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be quantified by using fluorescence imaging methods; (2 in atherosclerosis, dextranated MFNPs preferentially target macrophages; and (3 MFNP deposition in murine atheroma can be noninvasively detected by in vivo MRI. This study thus provides a foundation for using MFNPs to image genetic and/or pharmacological perturbations of cellular inflammation in experimental atherosclerosis and for the future development of novel targeted nanomaterials for atherosclerosis.

  2. Molecular genetics and gene expression in atherosclerosis

    NARCIS (Netherlands)

    Doevendans, P. A.; Jukema, W.; Spiering, W.; Defesche, J. C.; Kastelein, J. J.

    2001-01-01

    Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically

  3. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

    2015-01-01

    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

  4. Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Kjær, Andreas

    2015-01-01

    Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both ...

  5. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  6. Imaging subclinical atherosclerosis: is it ready for prime time? A review.

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    Fernández-Friera, Leticia; Ibáñez, Borja; Fuster, Valentín

    2014-10-01

    Imaging subclinical atherosclerosis holds the promise of individualized cardiovascular (CV) risk assessment. The large arsenal of noninvasive imaging techniques available today is playing an increasingly important role in the diagnosis and monitoring of subclinical atherosclerosis. However, there is a debate about the advisability of clinical screens for subclinical atherosclerosis and which modality is the most appropriate for monitoring risk and atherosclerosis progression. This article offers an overview of the traditional and emerging noninvasive imaging modalities used to detect early atherosclerosis, surveys population studies addressing the value of subclinical atherosclerosis detection, and also examines guideline recommendations for their clinical implementation. The clinical relevance of this manuscript lies in the potential of current imaging technology to improve CV risk prediction based on traditional risk factors and the present recommendations for subclinical atherosclerosis assessment. Noninvasive imaging will also help to identify individuals at high CV who would benefit from intensive prevention or therapeutic interventions.

  7. Molecular imaging of vulnerable atherosclerosis. Preclinical and clinical evaluation of nuclear tracers; Imagerie moleculaire de la plaque d'atherome vulnerable. Evaluation preclinique et clinique de traceurs radioactifs

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    Broisat, A.; Riou, L.M.; Dimastromatteo, J.; Pons, G.; Fagret, D.; Ghezzi, C. [Inserm U877, radiopharmaceutiques biocliniques, 38 - Grenoble (France); Grenoble Univ., 38 (France); Dimastromatteo, J. [ERAS Labo, 38 - Saint-Nazaire-les-Eymes (France)

    2009-02-15

    Atherosclerotic cardiovascular diseases (C.V.D.) are the leading cause of mortality worldwide, accounting for greater than 19.106 deaths annually. Despite major advances in the treatment of C.V.D., a high proportion of C.V.D. victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. Indeed, an acute heart attack is the first symptom of atherosclerosis in as much as 50% of individuals with severe disease. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerosis in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could potentially allow the identification of vulnerable patients by non-invasive scintigraphic imaging following administration of a radiolabeled tracer. The development of radiolabeled probes that specifically bind to and allow the in vivo imaging of vulnerable atherosclerotic plaques is therefore the subject of intense ongoing experimental and clinical research. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET imaging. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable atherosclerotic plaques in the carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of the coronary arteries remains a challenging issue because of the small size of atherosclerotic lesions and of their vicinity with blood and the circulating tracer activity. (authors)

  8. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

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    Wouter W. Jansen Klomp

    2016-01-01

    Full Text Available The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical open and closed chest procedures such as transaortic heart valve implantation. Several techniques are available to screen the ascending aorta, for example, transesophageal echocardiography (TEE, epiaortic ultrasound, TEE A-view method, manual palpation, computed tomography, and magnetic resonance imaging. This paper provides a description of the advantages and disadvantages of these imaging techniques.

  9. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

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    Jansen Klomp, Wouter W.; Brandon Bravo Bruinsma, George J.; van 't Hof, Arnoud W.; Grandjean, Jan. G.; Nierich, Arno P.

    2016-01-01

    The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical open and closed chest procedures such as transaortic heart valve implantation. Several techniques are available to screen the ascending aorta, for example, transesophageal echocardiography (TEE), epiaortic ultrasound, TEE A-view method, manual palpation, computed tomography, and magnetic resonance imaging. This paper provides a description of the advantages and disadvantages of these imaging techniques. PMID:26966580

  10. Optical imaging innovations for atherosclerosis research: multiphoton microscopy and optical nanoscopy.

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    Megens, Remco T A; Bianchini, Mariaelvy; Schmitt, Martin M N; Weber, Christian

    2015-06-01

    Cardiovascular disease is the leading cause of death and morbidity worldwide. Improving vascular prevention and therapy based on a refined mechanistic pervasion of atherosclerosis as the underlying pathology could limit the effect of vascular disease in aging societies. During the past decades, microscopy has contributed greatly to a better understanding of vascular physiology and pathology by allowing imaging of living specimen with subcellular resolution and high specificity. An important advance has been accomplished through the application of multiphoton microscopy in the vascular domain, a technological development that enabled multidimensional and dynamic imaging deep into the cellular architecture of intact tissue under physiological conditions. To identify and validate new targets for treating atherosclerosis, novel imaging strategies with nanoscale resolution will be essential to visualize molecular processes in intracellular and extracellular compartments. This review will discuss the current use of 2-photon microscopy and will provide an overview and outlook on options for introducing nanoscopic optical imaging modalities in atherosclerosis research. © 2015 American Heart Association, Inc.

  11. ARFI imaging for noninvasive material characterization of atherosclerosis.

    Science.gov (United States)

    Dumont, Douglas; Behler, Russell H; Nichols, Timothy C; Merricks, Elizabeth P; Gallippi, Caterina M

    2006-11-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States, with 70% of CVD mortalities the result of sequelae of atherosclerosis. An urgent need for enhanced delineation of vulnerable plaques has catalyzed the development of novel atherosclerosis imaging strategies that use X-ray computed tomography, magnetic resonance and ultrasound modalities. As suggested by the pathophysiology of plaque development and progression to vulnerability, insight to the focal material, i.e., mechanical, properties of arterial walls and plaques may enhance atherosclerosis characterization. We present acoustic radiation force impulse (ARFI) ultrasound in application to mechanically characterizing a raised focal atherosclerotic plaque in an iliac artery extracted from a relevant pig model. ARFI results are correlated to matched immunohistochemistry, indicating elastin and collagen composition. In regions of degraded elastin, slower recovery rates from peak ARFI-induced displacements were observed. In regions of collagen deposition, lower ARFI-induced displacements were achieved. This work demonstrates ARFI for characterizing the material nature of an atherosclerotic plaque.

  12. Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors.

    Science.gov (United States)

    Nahrendorf, Matthias; Waterman, Peter; Thurber, Greg; Groves, Kevin; Rajopadhye, Milind; Panizzi, Peter; Marinelli, Brett; Aikawa, Elena; Pittet, Mikael J; Swirski, Filip K; Weissleder, Ralph

    2009-10-01

    Proteases are emerging biomarkers of inflammatory diseases. In atherosclerosis, these enzymes are often secreted by inflammatory macrophages, digest the extracellular matrix of the fibrous cap, and destabilize atheromata. Protease function can be monitored with protease activatable imaging probes and quantitated in vivo by fluorescence molecular tomography (FMT). To address 2 major constraints currently associated with imaging of murine atherosclerosis (lack of highly sensitive probes and absence of anatomic information), we compared protease sensors (PS) of variable size and pharmacokinetics and coregistered FMT datasets with computed tomography (FMT-CT). Coregistration of FMT and CT was achieved with a multimodal imaging cartridge containing fiducial markers detectable by both modalities. A high-resolution CT angiography protocol accurately localized fluorescence to the aortic root of atherosclerotic apoE(-/-) mice. To identify suitable sensors, we first modeled signal kinetics in-silico and then compared 3 probes with oligo-L-lysine cleavage sequences: PS-5, 5 nm in diameter containing 2 fluorochromes, PS-25, a 25-nm version with an elongated lysine chain and PS-40, a polymeric nanoparticle. Serial FMT-CT showed fastest kinetics for PS-5 but, surprisingly, highest fluorescence in lesions of the aortic root for PS-40. PS-40 robustly reported therapeutic effects of atorvastatin, corroborated by ex vivo imaging and qPCR for the model protease cathepsin B. FMT-CT is a robust and observer-independent tool for noninvasive assessment of inflammatory murine atherosclerosis. Reporter-containing nanomaterials may have unique advantages over small molecule agents for in vivo imaging.

  13. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

    2013-02-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  14. Imaging of atherosclerosis: study design and cardiovascular risk prediction

    NARCIS (Netherlands)

    Peters, S.A.E.|info:eu-repo/dai/nl/341652326

    2012-01-01

    Cardiovascular disease is still the leading cause of morbidity and mortality worldwide.1 The majority of cardiovascular disease events is caused by atherosclerosis. Atherosclerosis is a slow and progressive disease of the arterial wall that is on the pathway between the effects of exposure to risk

  15. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Munnink, T. H. Oude; Nagengast, W. B.; Brouwers, A. H.; Schroder, C. P.; Hospers, G. A.; Lub-de Hooge, M. N.; van der Wall, E.; van Diest, P. J.; de Vries, E. G. E.

    2009-01-01

    Molecular imaging of breast cancer can potentially be used for breast cancer screening, staging, restaging, response evaluation and guiding therapies. Techniques for molecular breast cancer imaging include magnetic resonance imaging (MRI), optical imaging, and radionuclide imaging with positron

  16. Molecular characterization of Chlamydia pneumoniae associated to atherosclerosis.

    Science.gov (United States)

    Yazouli, Loubna El; Criscuolo, Alexis; Hejaji, Hicham; Bouaaza, Mohamed; Elmdaghri, Naima; Alami, Aziz Aroussi; Amraoui, Abderahim; Dakka, Nadia; Radouani, Fouzia

    2017-04-06

    Chlamydia pneumoniae is a respiratory pathogen associated with chronic inflammatory diseases such as asthma and atherosclerosis, and its detection in human carotid and coronary atheroma suggests some support for its involvement in atherogenesis. The main objective of our study was to evaluate the association between Chlamydia pneumoniae and atherosclerosis in Moroccan patients through a case/control approach and detected strain genotyping. A total of 137 cases and 124 controls were enrolled, nested PCR was performed for Chlamydia pneumoniae screening of the peripheral blood mononuclear cells (PBMCs) of both cases and controls as well as atheroma plaques from 37 cases, and positive samples were subjected to sequencing for genotyping and phylogenetic analysis. The results showed 54% and 18%, respectively, for positivity in cases and control PBMCs and 86.5% in atheroma plaques, the difference being significant between the two groups (pChlamydia pneumoniae in atherosclerosis in the studied population and genotyping revealed that detected strains were identical to human strains circulating worldwide. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Nanoplatform-based molecular imaging

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2011-01-01

    "Nanoplathform-Based Molecular Imaging provides rationale for using nanoparticle-based probes for molecular imaging, then discusses general strategies for this underutilized, yet promising, technology...

  18. Molecular Imaging Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Kovac, S.

    2009-05-01

    Full Text Available Molecular imaging mass spectrometry (IMS is a recently developed method for direct determination of spatial distribution of biopolymers, preferably proteins on cell surface and tissues. Imaging mass spectrometry data are mainly based on Matrix-Assisted Laser Desorption/Ionization- Time of Flight (MALDI TOF. The MALDI TOF based imaging mass spectrometry was applied for determination of changes in kidney tissue of sensitive mice after poisoning with aristolochic acid I. The second application presented here were changes in the gastric tissue in mice after infection with Helicobacter pylori, as a model of gastric cancer in humans caused by this pathogen microorganism. Molecular imaging mass spectrometry can be applied in medicine, mostly for identification of candidate biomarkers for malignant and non-malignant diseases. Furthermore, imaging MS has almost unlimited capacity in agriculture, food technology and biotechnology, e. g. for monitoring, process development and quality control of manufactured tissue of animal, plant and microbial origin.

  19. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

    NARCIS (Netherlands)

    Jansen Klomp, W.W.; Jansen Klomp, W.W.; Brandon Bravo Bruinsma, G.J.; van 't Hof, A.W.; Grandjean, Jan G; Nierich, A.P.

    2016-01-01

    The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical

  20. ARFI imaging for noninvasive material characterization of atherosclerosis. Part II: toward in vivo characterization.

    Science.gov (United States)

    Behler, Russell H; Nichols, Timothy C; Zhu, Hongtu; Merricks, Elizabeth P; Gallippi, Caterina M

    2009-02-01

    Seventy percent of cardiovascular disease (CVD) deaths are attributed to atherosclerosis. Despite their clinical significance, nonstenotic atherosclerotic plaques are not effectively detected by conventional atherosclerosis imaging methods. Moreover, conventional imaging methods are insufficient for describing plaque composition, which is relevant to cardiovascular risk assessment. Atherosclerosis imaging technologies capable of improving plaque detection and stratifying cardiovascular risk are needed. Acoustic radiation force impulse (ARFI) ultrasound, a novel imaging method for noninvasively differentiating the mechanical properties of tissue, is demonstrated for in vivo detection of nonstenotic plaques and plaque material assessment in this pilot investigation. In vivo ARFI imaging was performed on four iliac arteries: (1) of a normocholesterolemic pig with no atherosclerosis as a control, (2) of a familial hypercholesterolemic pig with diffuse atherosclerosis, (3) of a normocholesterolemic pig fed a high-fat diet with early atherosclerotic plaques and (4) of a familial hypercholesterolemic pig with diffuse atherosclerosis and a small, minimally occlusive plaque. ARFI results were compared with spatially matched immunohistochemistry, showing correlations between elastin and collagen content and ARFI-derived peak displacement and recovery time parameters. Faster recoveries from ARFI-induced peak displacements and smaller peak displacements were observed in areas of higher elastin and collagen content. Importantly, spatial correlations between tissue content and ARFI results were consistent and observable in large and highly evolved as well as small plaques. ARFI imaging successfully distinguished nonstenotic plaques, while conventional B-mode ultrasound did not. This work validates the potential relevance of ARFI imaging as a noninvasive imaging technology for in vivo detection and material assessment of atherosclerotic plaques.

  1. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

    This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

  2. Vascular targeting of nanoparticles for molecular imaging of diseased endothelium.

    Science.gov (United States)

    Atukorale, Prabhani U; Covarrubias, Gil; Bauer, Lisa; Karathanasis, Efstathios

    2017-04-01

    This review seeks to highlight the enormous potential of targeted nanoparticles for molecular imaging applications. Being the closest point-of-contact, circulating nanoparticles can gain direct access to targetable molecular markers of disease that appear on the endothelium. Further, nanoparticles are ideally suitable to vascular targeting due to geometrically enhanced multivalent attachment on the vascular target. This natural synergy between nanoparticles, vascular targeting and molecular imaging can provide new avenues for diagnosis and prognosis of disease with quantitative precision. In addition to the obvious applications of targeting molecular signatures of vascular diseases (e.g., atherosclerosis), deep-tissue diseases often manifest themselves by continuously altering and remodeling their neighboring blood vessels (e.g., cancer). Thus, the remodeled endothelium provides a wide range of targets for nanoparticles and molecular imaging. To demonstrate the potential of molecular imaging, we present a variety of nanoparticles designed for molecular imaging of cancer or atherosclerosis using different imaging modalities. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Comparison of synthetic HDL contrast agents for MR imaging of atherosclerosis

    Science.gov (United States)

    Cormode, David P.; Chandrasekar, Rohith; Delshad, Amanda; Briley-Saebo, Karen C.; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J. M.

    2009-01-01

    Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here we compare the efficacy of two synthetic, HDL-based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 nm and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mMs)-1. 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of ~90% (n=7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 hours, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI. PMID:19378935

  4. Comparison of synthetic high density lipoprotein (HDL) contrast agents for MR imaging of atherosclerosis.

    Science.gov (United States)

    Cormode, David P; Chandrasekar, Rohith; Delshad, Amanda; Briley-Saebo, Karen C; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J M; Fisher, Edward A; Fayad, Zahi A

    2009-05-20

    Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here, we compare the efficacy of two synthetic, high density lipoprotein (HDL) based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mM s)(-1). 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of approximately 90% (n = 7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 h, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI.

  5. Molecular Biomedical Imaging Laboratory (MBIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Molecular Biomedical Imaging Laboratory (MBIL) is adjacent-a nd has access-to the Department of Radiology and Imaging Sciences clinical imaging facilities. MBIL...

  6. Molecular mechanisms of felodipine suppressing atherosclerosis in high-cholesterol-diet apolipoprotein E-knockout mice.

    Science.gov (United States)

    Yao, Rui; Cheng, Xiang; Liao, Yu-Hua; Chen, Yong; Xie, Jiang-Jiao; Yu, Xian; Ding, Ying-Jun; Tang, Ting-Ting

    2008-02-01

    Oxidative stress and inflammation processes are key components of atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. Evidence has revealed that calcium-channel blockers (CCB) could retard atherogenesis, but the exact mechanisms have not been fully elucidated. The present study was undertaken to investigate the potential effects and molecular mechanisms of the CCB felodipine on the process of atherosclerosis in high-cholesterol-diet (HCD) apolipoprotein E-knockout (ApoE KO) mice. Adult male ApoE KO mice were given a normal diet (ND) or HCD and were randomized to no treatment or felodipine (5 mg / kg per day for 12 weeks). The ApoE KO mice with HCD were associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, and the expressions of NADPH oxidase subunits (p47 and Rac-1), nuclear factor-kappaB (NF-kappaB) in nucleus, phosphor-inhibitors of kappaB (p-IkappaB), tumor necrosis-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and vascular cell-adhesion molecule-1 (VCAM-1). These changes were suppressed in mice that were treated with felodipine (5 mg/kg per day for 12 weeks) concomitant with HCD administration, with no significant change in systolic blood pressure and plasma lipid levels. The results suggest that felodipine can attenuate atherosclerosis, and this effect is partly related to inhibition of oxidative stress and inflammatory signal-transduction pathways, which lead to decreases in the expression of inflammatory cytokines.

  7. Molecular analysis of the GSTT1 gene polymorphism in patients with clinical manifestation of atherosclerosis.

    Science.gov (United States)

    Martins, J V M; Rodrigues, D A; Silva, K S F; Costa, I R; Lagares, M H; Campedelli, F L; Barbosa, A M; Morais, M P; Moura, K K V O

    2017-07-06

    Atherosclerosis is a chronic inflammatory disease formed by the accumulation of lipids in the innermost layer and large-caliber artery (tunica intima). This accumulation, along with platelet factors, stimulates the proliferation of muscle cells in this region. Over than 400 genes may be related to the pathology since they regulate endothelial function, coagulation, inflammation, metabolism of amino acids, lipids, and carbohydrates. Glutathione S-transferases (GST) are enzymes that catalyze the polymorphic detoxification of metabolites produced by oxidative stress within the cells, which is induced by reactive oxygen species. GSTs are one of the defense mechanisms against oxidative stress damage. Due to genetic, cultural, and environmental factors, the rate of atherosclerosis is higher; however, an early diagnosis is crucial for the prevention and treatment of several complications related to the disease. The present study aimed to analyze the frequency of GSTT1 genotypes regarding the presence or absence of the polymorphism in patients with clinical manifestation of atherosclerosis. We collected 200 samples of peripheral blood of patients with the previous diagnosis of atherosclerosis based on clinical examination and imaging, and 100 samples of peripheral blood to compose the control group of patients without clinical manifestation of atherosclerosis. The polymorphism was assessed by PCR and analyzed on the agarose gel stained with 2.0% ethidium bromide. The frequency of the GSTT1 gene polymorphism was compared using the chi-square test (P < 0.05) and the G-test. In the case group, we detected 85.5% of patients with the GSTT1 genotype present and 14.5% of patients with the null genotype. A significant difference was observed between groups (case vs control) for the presence of the GSTT1 polymorphism. According to the analysis of the variable alcohol consumption, we found that in the case group the presence of the GSTT1 gene was higher in individuals who reported

  8. Graphical modeling of gene expression in monocytes suggests molecular mechanisms explaining increased atherosclerosis in smokers.

    Science.gov (United States)

    Verdugo, Ricardo A; Zeller, Tanja; Rotival, Maxime; Wild, Philipp S; Münzel, Thomas; Lackner, Karl J; Weidmann, Henri; Ninio, Ewa; Trégouët, David-Alexandre; Cambien, François; Blankenberg, Stefan; Tiret, Laurence

    2013-01-01

    Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA) and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path "smoking→gene expression→plaques". Robustness of the causal inference was assessed by bootstrapping. At a FDR ≤0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the "smoking→gene expression→plaques" causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts. Inspection of

  9. Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice

    Directory of Open Access Journals (Sweden)

    Fei Yan

    2015-01-01

    Full Text Available The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein- targeted microparticles of iron oxide (CD81-MPIO for magnetic resonance imaging (MRI of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G- MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P<0.01. Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging.

  10. Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis

    Science.gov (United States)

    Jo, Javier A.; Park, Jesung; Pande, Paritosh; Shrestha, Sebina; Serafino, Michael J.; Rico Jimenez, J. de Jesus; Clubb, Fred; Walton, Brian; Buja, L. Maximilian; Phipps, Jennifer E.; Feldman, Marc D.; Adame, Jessie; Applegate, Brian E.

    2015-01-01

    Aims The aim of this study was to validate novel imaging technology for simultaneous morphological and biochemical endogenous optical imaging of coronary atherosclerotic plaque. Methods and results Optical coherence tomography (OCT) generates high-resolution 3D images of plaque morphology and endogenous fluorescence lifetime imaging microscopy (FLIM) characterizes biochemical composition. Both imaging modalities rely on plaque's intrinsic optical characteristics, making contrast agents unnecessary. A multimodal OCT/FLIM system was utilized to generate luminal biochemical maps superimposed on high-resolution (7 µm axial and 13 µm lateral) structural volumetric images. Forty-seven fresh postmortem human coronary segments were imaged: pathological intimal thickening (PIT, n = 26), fibroatheroma (FA, n = 12), thin-cap FA (TCFA, n = 2), and fibrocalcific plaque (CA, n = 7), determined by histopathology. Multimodal images were evaluated, and each plaque identified as PIT, FA, TCFA, or CA based on expert OCT readers, and as having high-lipid (HL), high-collagen (HC), or low-collagen/low-lipid (LCL) luminal composition based on linear discriminant analysis of FLIM. Of 47 plaques, 89.4% (42/47) of the plaques were correctly identified based on OCT/FLIM evaluation using tissue histopathology and immunohistochemistry as the gold standard. Four of the misclassifications corresponded to confusing PIT with HL luminal composition for FA with HL cap. The other corresponded to confusing FA with a HC cap for FA with an LCL cap. Conclusion We have demonstrated the feasibility of accurate simultaneous OCT/FLIM morphological and biochemical characterization of coronary plaques at spatial resolutions and acquisition speeds compatible with catheter-based intravascular imaging. The success of this pilot study sets up future development of a multimodal intravascular imaging system that will enable studies that could help improve our understanding of plaque pathogenesis. PMID:25722204

  11. Assessment of plaque vulnerability in atherosclerosis via intravascular photoacoustic imaging of targeted liposomal ICG J-aggregates (Conference Presentation)

    Science.gov (United States)

    Harris, Justin T.; Dumani, Diego S.; Cook, Jason R.; Sokolov, Konstantin V.; Emelianov, Stanislav Y.; Homan, Kimberly A.

    2017-03-01

    While molecular and cellular imaging can be used to visualize the conventional morphology characteristics of vulnerable plaques, there is a need to monitor other physiological factors correlated with high rupture rates; a high M1 activated macrophage concentration is one such indicator of high plaque vulnerability. Here, we present a molecularly targeted contrast agent for intravascular photoacoustic (IVPA) imaging consisting of liposomes loaded with indocyanine green (ICG) J-aggregates with high absorption at 890 nm, allowing for imaging in the presence of blood. This "Lipo-ICG" was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes accumulate in plaques through areas of endothelial dysfunction, while the liposome encapsulation prevents nonspecific interaction with lipids and endothelium. Lipo-ICG specifically interacts with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. This sensing mechanism enables assessment of the M1 activated macrophage concentration, providing a measure of plaque vulnerability. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls. Thus, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection, allowing better clinical decision making in treatment of atherosclerosis.

  12. Magnetic resonance imaging of atherosclerosis : studies in visceral obesity

    NARCIS (Netherlands)

    Alizadeh Dehnavi, Reza

    2009-01-01

    The aim of this thesis was to explore the relation between visceral obesity and the accompanying metabolic disturbances, systemic inflammation and the atherosclerotic process. A newly developed magnetic resonance vessel wall imaging technique was implemented in phenotyping patients and as a

  13. Bioluminescence imaging of energy depletion in vascular pathology: patent ductus arteriosus and atherosclerosis.

    Science.gov (United States)

    Leppänen, Olli; Ekstrand, Matias; Bräsen, Jan Hinrich; Levin, Max

    2012-04-01

    The artery wall may develop energy depletion due to insufficient nutritional supply. However, until recently it has not been possible to validate this hypothesis because no available technology has allowed assessment of energy metabolism with sufficient spatial resolution. We use high resolution bioluminescence metabolic imaging to study energy metabolism in two mechanistically different vascular pathologies: patent ductus arteriosus and atherosclerosis. Physiological energy depletion in postnatally constricting ductus arteriosus promotes permanent closure. Insufficient ductus energy depletion, common in preterm infants, is associated with persistent patent ductus arteriosus, a condition with significantly increased morbidity and mortality. In contrast, in atherosclerosis, energy depletion in the macrophage-rich lesion core promotes cell death contributing to lesion instability and disease progression. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Tumor Molecular Imaging with Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhen Cheng

    2016-03-01

    Full Text Available Molecular imaging (MI can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques. Over the past decade, the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects. It is expected that multimodality nanoparticles (NPs can lead to precise assessment of tumor biology and the tumor microenvironment. This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging, ultrasound, photoacoustic imaging, magnetic resonance imaging (MRI, and radionuclide imaging. Key challenges involved in the translation of NPs to the clinic are discussed.

  15. Molecular photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Frogh Jafarian Dehkordi

    2015-04-01

    Full Text Available Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods: In this review, using keywords such as photoacoustic, optoacoustic, laser-ultrasound, thermoacoustic at databases such as PubMed and ISI, studies performed in the field of photoacoustic and related findings were evaluated. Results: Photoacoustic imaging, acquiring images with high contrast and desired resolution, provides an opportunity to perform physiologic and anatomic studies. Because this technique does not use ionizing radiation, it is not restricted by the limitation of the ionizing-based imaging systems therefore it can be used noninvasively to make images from cell, vessels, whole body imaging of the animal and distinguish tumor from normal tissue. Conclusion: Photoacoustic imaging is a new method in preclinical researches which can be used in various physiologic and anatomic studies. This method, because of application of non-ionizing radiation, may resolve limitation of radiation based method in diagnostic assessments.

  16. Imaging arterial cells, atherosclerosis, and restenosis by multimodal nonlinear optical microscopy

    Science.gov (United States)

    Wang, Han-Wei; Simianu, Vlad; Locker, Matthew J.; Sturek, Michael; Cheng, Ji-Xin

    2008-02-01

    By integrating sum-frequency generation (SFG), and two-photon excitation fluorescence (TPEF) on a coherent anti-Stokes Raman scattering (CARS) microscope platform, multimodal nonlinear optical (NLO) imaging of arteries and atherosclerotic lesions was demonstrated. CARS signals arising from CH II-rich membranes allowed visualization of endothelial cells and smooth muscle cells in a carotid artery. Additionally, CARS microscopy allowed vibrational imaging of elastin and collagen fibrils which are rich in CH II bonds in their cross-linking residues. The extracellular matrix organization was further confirmed by TPEF signals arising from elastin's autofluorescence and SFG signals arising from collagen fibrils' non-centrosymmetric structure. The system is capable of identifying different atherosclerotic lesion stages with sub-cellular resolution. The stages of atherosclerosis, such as macrophage infiltration, lipid-laden foam cell accumulation, extracellular lipid distribution, fibrous tissue deposition, plaque establishment, and formation of other complicated lesions could be viewed by our multimodal CARS microscope. Collagen percentages in the region adjacent to coronary artery stents were resolved. High correlation between NLO and histology imaging evidenced the validity of the NLO imaging. The capability of imaging significant components of an arterial wall and distinctive stages of atherosclerosis in a label-free manner suggests the potential application of multimodal nonlinear optical microscopy to monitor the onset and progression of arterial diseases.

  17. Advances in multimodal molecular imaging.

    Science.gov (United States)

    Auletta, Luigi; Gramanzini, Matteo; Gargiulo, Sara; Albanese, Sandra; Salvatore, Marco; Greco, Adelaide

    2017-03-01

    Preclinical molecular imaging is an emerging field. Improving the ability of scientists to study the molecular basis of human pathology in animals is of the utmost importance for future advances in all fields of human medicine. Moreover, the possibility of developing new imaging techniques or of implementing old ones adapted to the clinic is a significant area. Cardiology, neurology, immunology and oncology have all been studied with preclinical molecular imaging. The functional techniques of photoacoustic imaging (PAI), fluorescence molecular tomography (FMT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in association with each other or with the anatomic reference provided by computed tomography (CT) as well as with anatomic and functional information provided by magnetic resonance (MR) have all been proficiently applied to animal models of human disease. All the above-mentioned imaging techniques have shown their ability to explore the molecular mechanisms involved in animal models of disease. The clinical translatability of most of the techniques motivates the ongoing study of their possible fields of application. The ability to combine two or more techniques allows obtaining as much information as possible on the molecular processes involved in pathologies, reducing the number of animals necessary in each experiment. Merging molecular probes compatible with various imaging technique will further expand the capability to achieve the best results.

  18. In Vivo PET Imaging of HDL in Multiple Atherosclerosis Models

    DEFF Research Database (Denmark)

    Pérez-Medina, Carlos; Binderup, Tina; Lobatto, Mark E

    2016-01-01

    OBJECTIVES: The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities. BACKGROUND: HDL is a natural nanoparticle......,2-distearoyl-sn-glycero-3-phosphoethanolamine-deferoxamine B). Biodistribution and plaque targeting of radiolabeled HDL were studied in established murine, rabbit, and porcine atherosclerosis models by using PET combined with computed tomography (PET/CT) imaging or PET combined with magnetic resonance imaging......-injection for both (89)Zr-HDL nanoparticles. In the porcine model, increased accumulation of radioactivity was observed in lesions by using in vivo PET imaging. Irrespective of the radiolabel's location, HDL nanoparticles were able to preferentially target plaque macrophages and monocytes. CONCLUSIONS: (89)Zr...

  19. Nanodiamond imaging: a new molecular imaging approach.

    Science.gov (United States)

    Hegyi, Alex N; Yablonovitch, Eli

    2012-01-01

    A new molecular imaging approach is proposed that combines optical detection and magnetic field gradients to achieve high sensitivity and high spatial resolution. Called Nanodiamond Imaging, this new modality images the location of nanodiamonds within a living organism. Since nanodiamonds can be tagged with biologically active molecules and are nontoxic, Nanodiamond Imaging may become an important biomedical research tool with possible clinical application. A Nanodiamond Imaging system actually senses a particular type of defect in the nanodiamond called the nitrogen-vacancy center. A prototype system has been built that was tested by imaging an artificial target within a volume of chicken breast. The resolving power should be <100 µm with modest improvements, significantly finer than PET, SPECT, and in-vivo optical imaging. The sensitivity of the imaging system, taking into account foreseen improvements, should be better than a 10 nanomolar concentration of carbon atoms, referenced to a 1 mm(3) voxel volume and one second of measurement time (10 nM·mm(3)·Hz(-1/2))--a similar sensitivity to the other molecular imaging techniques, but with a stable, non-radioactive tracer.

  20. The role of atherosclerosis imaging in redefining normal and abnormal cholesterol values, and risk reduction in primary prevention statin trials.

    Science.gov (United States)

    Hecht, Harvey S

    2011-10-01

    The emergence of atherosclerosis imaging, using coronary calcium scanning (CAC) and carotid intima media thickness (CIMT) and plaque as stronger predictors of cardiovascular events than risk factors of atherosclerosis, has created a paradigm shift in the primary prevention of cardiovascular disease. Rather than population-derived indices to define normal or abnormal low-density lipoprotein (or other lipid values) in the untreated individual patient, it is more appropriate to define "normal" as "cholesterol values at which level there is no subclinical atherosclerosis" and "abnormal" as "cholesterol values at which level there is subclinical atherosclerosis," with the severity of "abnormal" depending on the degree of subclinical atherosclerosis. Similarly, the low-density lipoprotein treatment goal is the level at which atherosclerosis progression is halted. Extension of the subclinical atherosclerosis risk-based paradigms to primary prevention trials dramatically changes the manner in which trials should be conducted in the future, as well as the results of trials already performed. For example, asymptomatic patients with a CAC score of 0 have an extraordinarily low event rate but have been included in primary prevention statin trials even though their risk without treatment is very small. Reanalysis of the statin primary prevention trials after excluding the percentage (40%) of patients who would be expected to have a CAC score of 0 yields an absolute risk increase of 60% in both the placebo group (from 5.4% to 8.5%), and the statin group (from 3.0% to 4.8%). Absolute risk reduction increased by 58% (from 2.4% to 3.8%). Relative risk reduction of 44% was unchanged. In conclusion, 1) the presence or absence of atherosclerosis as measured by CAC redefines normal or abnormal lipid levels in an individual patient; 2) statin absolute risk reduction is significantly greater than previously appreciated; and 3) patients with a CAC score of 0 should be excluded from

  1. Molecular imaging. Fundamentals and applications

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Jie (ed.) [Chinese Academy of Sciences, Beijing (China). Intelligent Medical Research Center

    2013-07-01

    Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

  2. [Magnetic resonance tomography: potentials of molecular imaging].

    Science.gov (United States)

    Hiller, Karl-Heinz; Faber, Cornelius; Neuberger, Thomas; Köhler, Sascha; Stroh, Albrecht; Zimmer, Claus; Jakob, Peter

    2005-01-01

    Molecular imaging is "the in-vivo characterization and measurement of biological processes at the cellular and molecular level" and allows the imaging of molecular abnormalities associated with diseases long before morphological changes can be detected. At present, the use of magnetic resonance imaging (MRI) for molecular and cellular imaging is rapidly increasing. MRI is a very attractive candidate, since current MRI protocols already provide anatomic, functional, and biochemical information of excellent image quality and with high spatial resolution. Combining this high spatial resolution/high contrast imaging modality with specific MRI contrast imaging agents for molecular imaging is currently the focus of research in many laboratories worldwide. This paper summarizes the rationale for molecular MRI imaging and describes the basic features of modern molecular imaging strategies with MRI. Finally, a special focus is given to the growing field of applications, e.g., stem cell imaging, imaging of apoptosis, plaques, and other biological targets of interest.

  3. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  4. A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo

    Science.gov (United States)

    Wu, Chenxin; Zhang, Yejun; Li, Zhen; Li, Chunyan; Wang, Qiangbin

    2016-06-01

    Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe-/- mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications.Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively

  5. Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see.

    Science.gov (United States)

    Cocker, Myra S; Mc Ardle, Brian; Spence, J David; Lum, Cheemun; Hammond, Robert R; Ongaro, Deidre C; McDonald, Matthew A; Dekemp, Robert A; Tardif, Jean-Claude; Beanlands, Rob S B

    2012-12-01

    Prodigious efforts and landmark discoveries have led toward significant advances in our understanding of atherosclerosis. Despite significant efforts, atherosclerosis continues globally to be a leading cause of mortality and reduced quality of life. With surges in the prevalence of obesity and diabetes, atherosclerosis is expected to have an even more pronounced impact upon the global burden of disease. It is imperative to develop strategies for the early detection of disease. Positron emission tomography (PET) imaging utilizing [(18)F]fluorodeoxyglucose (FDG) may provide a non-invasive means of characterizing inflammatory activity within atherosclerotic plaque, thus serving as a surrogate biomarker for detecting vulnerable plaque. The aim of this review is to explore the rationale for performing FDG imaging, provide an overview into the mechanism of action, and summarize findings from the early application of FDG PET imaging in the clinical setting to evaluate vascular disease. Alternative imaging biomarkers and approaches are briefly discussed.

  6. Computer aided diagnosis of Coronary Artery Disease, Myocardial Infarction and carotid atherosclerosis using ultrasound images: A review.

    Science.gov (United States)

    Faust, Oliver; Acharya, U Rajendra; Sudarshan, Vidya K; Tan, Ru San; Yeong, Chai Hong; Molinari, Filippo; Ng, Kwan Hoong

    2017-01-01

    The diagnosis of Coronary Artery Disease (CAD), Myocardial Infarction (MI) and carotid atherosclerosis is of paramount importance, as these cardiovascular diseases may cause medical complications and large number of death. Ultrasound (US) is a widely used imaging modality, as it captures moving images and image features correlate well with results obtained from other imaging methods. Furthermore, US does not use ionizing radiation and it is economical when compared to other imaging modalities. However, reading US images takes time and the relationship between image and tissue composition is complex. Therefore, the diagnostic accuracy depends on both time taken to read the images and experience of the screening practitioner. Computer support tools can reduce the inter-operator variability with lower subject specific expertise, when appropriate processing methods are used. In the current review, we analysed automatic detection methods for the diagnosis of CAD, MI and carotid atherosclerosis based on thoracic and Intravascular Ultrasound (IVUS). We found that IVUS is more often used than thoracic US for CAD. But for MI and carotid atherosclerosis IVUS is still in the experimental stage. Furthermore, thoracic US is more often used than IVUS for computer aided diagnosis systems. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Double jeopardy: multi-modality imaging of monozygotic "twin cap" atherosclerosis.

    Science.gov (United States)

    Murray, Scott W; Cooper, Robert M; Appleby, Clare; McCann, Caroline; Binukrishnan, Sukumaran; Radu, Maria D; Stables, Rodney H

    2014-11-01

    The investigation of asymptomatic but potentially vulnerable atherosclerosis is not yet a major focus for clinical Cardiologists. We have illustrated the contemporary investigation and treatment of such disease using a clinical case that involved monozygotic twins. One twin (T1) had unfortunately suffered a cardiac arrest whilst jogging and survived only due to bystander CPR and prompt defibrillation. His identical twin brother (T2), on subsequent investigation, harbours a compositionally identical lesion in a proximal coronary vessel that has not yet ruptured or provoked a clinical event. Following the presentation of both non-invasive and invasive images, we discuss the need for active suspicion and intensive treatment for those people with a 'genetic' risk of future myocardial infarction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Molecular imaging with theranostic nanoparticles.

    Science.gov (United States)

    Jokerst, Jesse V; Gambhir, Sanjiv S

    2011-10-18

    Nanoparticles (NPs) offer diagnostic and therapeutic capabilities not available with small molecules or microscale tools. As the field of molecular imaging has emerged from the blending of molecular biology with medical imaging, NP imaging is increasingly common for both therapeutic and diagnostic applications. The term theranostic describes technology with concurrent and complementary diagnostic and therapeutic capabilities. Although NPs have been FDA-approved for clinical use as transport vehicles for nearly 15 years, full translation of their theranostic potential is incomplete. However, NPs have shown remarkable success in the areas of drug delivery and magnetic resonance imaging. Emerging applications include image-guided resection, optical/photoacoustic imaging in vivo, contrast-enhanced ultrasound, and thermoablative therapy. Diagnosis with NPs in molecular imaging involves the correlation of the signal with a phenotype. The location and intensity of NP signals emanating from a living subject indicate the disease area's size, stage, and biochemical signature. Therapy with NPs uses the image for resection or delivery of a small molecule or RNA therapeutic. Ablation of the affected area is also possible via heat or radioactivity. The ideal theranostic NP includes several features: (1) it selectively and rapidly accumulates in diseased tissue; (2) it reports biochemical and morphological characteristics of the area; (3) it delivers an effective therapeutic; and (4) it is safe and biodegrades with nontoxic byproducts. Such a system contains a central imaging core surrounded by small molecule therapeutics. The system targets via ligands such as IgG and is protected from immune scavengers by a cloak of protective polymer. Although no NP has achieved all of the above criteria, many NPs possess one or more of these features. While the most clinically translatable NPs have been used in the field of magnetic resonance imaging, other types in development are quickly

  9. Molecular Imaging with Theranostic Nanoparticles

    Science.gov (United States)

    Jokerst, Jesse V.; Gambhir, Sanjiv S.

    2011-01-01

    Conspectus Nanoparticles offer diagnostic and therapeutic capabilities impossible with small molecules or micro-scale tools. As molecular biology merges with medical imaging to form the field of molecular imaging, nanoparticle imaging is increasingly common with both therapeutic and diagnostic applications. The term theranostic indicates technology with concurrent and complementary diagnostic and therapeutic capabilities. When performed with sub-micron materials, the field may be termed theranostic nanomedicine. Although nanoparticles have been FDA-approved for clinical use as transport vehicles for nearly 15 years, full translation of their theranostic potential is incomplete. Still, remarkable successes with nanoparticles have been realized in the areas of drug delivery and magnetic resonance imaging. Emerging applications include image-guided resection, optical/photoacoustic imaging in vivo, contrast-enhanced ultrasound, and thermoablative therapy. Diagnosis with nanoparticles in molecular imaging involves correlating signal to a phenotype. The disease’s size, stage, and biochemical signature can be gleaned from the location and intensity of nanoparticle signal emanating from a living subject. Therapy with NP uses the image for resection or delivery of small molecule or RNA thererapeutic. Ablation of the affected area is also possible via heat or radioactivity. The ideal theranostic NP: (1) selectively and rapidly accumulates in diseased tissue, (2) reports biochemical and morphological characteristics of the area, (3) delivers a non-invasive therapeutic, and (4) is safe and biodegrades with non-toxic byproducts. Above is a schematic of such a system which contains a central imaging core (yellow) surrounded by small molecule therapeutics (red). The system targets via ligands such as IgG (pink) and is protected from immune scavengers by a cloak of protective polymer (green). While no nanoparticle has achieved all of the above features, many NPs do fulfill one

  10. Molecular imaging of brown adipose tissue in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

    2014-04-15

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  11. Molecular Imaging: Current Status and Emerging Strategies

    Science.gov (United States)

    Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

    2011-01-01

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

  12. In Vivo PET Imaging of HDL in Multiple Atherosclerosis Models.

    Science.gov (United States)

    Pérez-Medina, Carlos; Binderup, Tina; Lobatto, Mark E; Tang, Jun; Calcagno, Claudia; Giesen, Luuk; Wessel, Chang Ho; Witjes, Julia; Ishino, Seigo; Baxter, Samantha; Zhao, Yiming; Ramachandran, Sarayu; Eldib, Mootaz; Sánchez-Gaytán, Brenda L; Robson, Philip M; Bini, Jason; Granada, Juan F; Fish, Kenneth M; Stroes, Erik S G; Duivenvoorden, Raphaël; Tsimikas, Sotirios; Lewis, Jason S; Reiner, Thomas; Fuster, Valentín; Kjær, Andreas; Fisher, Edward A; Fayad, Zahi A; Mulder, Willem J M

    2016-08-01

    The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities. HDL is a natural nanoparticle that interacts with atherosclerotic plaque macrophages to facilitate reverse cholesterol transport. HDL-cholesterol concentration in blood is inversely associated with risk of coronary heart disease and remains one of the strongest independent predictors of incident cardiovascular events. Discoidal HDL nanoparticles were prepared by reconstitution of its components apolipoprotein A-I (apo A-I) and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine. For radiolabeling with zirconium-89 ((89)Zr), the chelator deferoxamine B was introduced by conjugation to apo A-I or as a phospholipid-chelator (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-deferoxamine B). Biodistribution and plaque targeting of radiolabeled HDL were studied in established murine, rabbit, and porcine atherosclerosis models by using PET combined with computed tomography (PET/CT) imaging or PET combined with magnetic resonance imaging. Ex vivo validation was conducted by radioactivity counting, autoradiography, and near-infrared fluorescence imaging. Flow cytometric assessment of cellular specificity in different tissues was performed in the murine model. We observed distinct pharmacokinetic profiles for the two (89)Zr-HDL nanoparticles. Both apo A-I- and phospholipid-labeled HDL mainly accumulated in the kidneys, liver, and spleen, with some marked quantitative differences in radioactivity uptake values. Radioactivity concentrations in rabbit atherosclerotic aortas were 3- to 4-fold higher than in control animals at 5 days' post-injection for both (89)Zr-HDL nanoparticles. In the porcine model, increased accumulation of radioactivity was observed in lesions by using in vivo PET imaging. Irrespective of the

  13. Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

    Science.gov (United States)

    Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

    2015-09-01

    The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Label-free molecular imaging

    Science.gov (United States)

    Zhang, Junqi; Li, Qi; Fu, Rongxin; Wang, Tongzhou; Wang, Ruliang; Huang, Guoliang

    2014-03-01

    Optical microscopy technology has achieved great improvements in the 20th century. The detection limit has reached about twenty nanometers (with near-field optics, STED, PALM and STORM). But in the application areas such as life science, medical science, clinical treatment and especially in vivo dynamic measurement, mutual restrictions still exist between numeric aperture/magnification and working distance, fluorescent dependent, and between resolution and frame rate/field size, etc. This paper explores a hyperspectral scanning super-resolution label free molecules imaging method based on the white light interferometry. The vertical detection resolution was approximate to 1 nm which is the thickness of a single molecular layer and dynamic measuring range of thickness reaches to 10 μm. The spectrum-shifting algorithm is developed for robust restructure of images when the pixels are overlapped. Micro-biochip with protein binding and DNA amplification could be detected by using this spectral scanning super-resolution molecules imaging in label free. This method has several advantages as following: Firstly, the decoding and detecting steps are combined into one step. It makes tests faster and easier. Secondly, we used thickness-coded, minimized chips instead of a large microarray chip to carry the probes. This accelerates the interaction of the biomolecules. Thirdly, since only one kind of probes are attached to our thickness-coded, minimized chip, users can only pick out the probes they are interested in for a test without wasting unnecessary probes and chips.

  15. 2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis

    NARCIS (Netherlands)

    Tahara, Nobuhiro; Mukherjee, Jogeshwar; de Haas, Hans J; Petrov, Artiom D; Tawakol, Ahmed; Haider, Nezam; Tahara, Atsuko; Constantinescu, Cristian C; Zhou, Jun; Boersma, Hendrikus H; Imaizumi, Tsutomu; Nakano, Masataka; Finn, Aloke; Fayad, Zahi; Virmani, Renu; Fuster, Valentin; Bosca, Lisardo; Narula, Jagat

    Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because

  16. Procesos moleculares patogénicos de la aterosclerosis y alternativas terapéuticas para su control Pathogenic molecular processes of atherosclerosis and therapeutic alternatives for control

    Directory of Open Access Journals (Sweden)

    Livan Delgado Roche

    2012-06-01

    Full Text Available La aterosclerosis es una enfermedad vascular crónica que afecta las bifurcaciones de las grandes arterias. Las enfermedades cardiovasculares asociadas a esta afección representan la primera causa de mortalidad en el mundo occidental. La fisiopatología de la aterosclerosis interrelaciona una serie de fenómenos moleculares y celulares complejos que aún no están del todo esclarecidos. Sin embargo, se han postulado algunas hipótesis para dar explicación a los procesos patogénicos que tienen lugar durante la aterogénesis. El objetivo del presente trabajo es ofrecer una actualización sobre los principales cambios moleculares que ocurren durante el inicio y progreso de esta enfermedad, así como las alternativas terapéuticas para su tratamiento y control. Para ello se realizó una revisión de publicaciones científicas en la base de datos MEDLINE durante los últimos 10 años. Se profundizó en la complejidad de dicha afección y se demostró que aún no existe una terapia totalmente eficaz para su tratamiento.Atherosclerosis is a chronic vascular disease which affects bifurcations of major arteries. Atherosclerosis-associated cardiovascular diseases represent the first cause of mortality in the western world. The physiopathology of atherosclerosis associates a variety of molecular and cellular complex events, which are not completely understood. However, some hypothesis have been postulated to explain the pathogenic events during atherogenesis. The objective of the present article is to offer an updating on the principal molecular events during the atherosclerosis development and therapeutic alternatives for its treatment and control. To this end, a literature review was made in MEDLINE database, which covered the scientific publications of the last 10 years. The complexity of this illness was analyzed in depth and it was demonstrated that there was not any completely effective therapy to treat it.

  17. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Bucerius, Jan [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); University Hospital RWTH Aachen, RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center (MUMC), Department of Nuclear Medicine and Cardiovascular Research Institute (CARIM), P. Debyelaan 25, HX, Maastricht (Netherlands); Hyafil, Fabien [Bichat University Hospital, Inserm 1148, DHU FIRE, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Verberne, Hein J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging, Faculty of Science and Technology, Enschede (Netherlands); Lindner, Oliver [Heart and Diabetes Center NRW, Nuclear Medicine and Molecular Imaging, Institute of Radiology, Bad Oeynhausen (Germany); Sciagra, Roberto [University of Florence, Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, Florence (Italy); Agostini, Denis [Normandie Universite, Department of Nuclear Medicine, CHU Cote de Nacre, Caen (France); Uebleis, Christopher [Ludwig-Maximilians Universitaet Muenchen, Department of Clinical Radiology, Muenchen (Germany); Gimelli, Alessia [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Hacker, Marcus [Medical University Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided therapy, Vienna (Austria); Collaboration: on behalf of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM)

    2016-04-15

    Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as ''strict guidelines'' but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards &apos

  18. Atherosclerosis: contrast-enhanced MR imaging of vessel wall in rabbit model--comparison of gadofosveset and gadopentetate dimeglumine.

    Science.gov (United States)

    Lobbes, Marc B I; Miserus, Robbert-Jan J H M; Heeneman, Sylvia; Passos, Valeria Lima; Mutsaers, Peter H A; Debernardi, Nicola; Misselwitz, Bernd; Post, Mark; Daemen, Mat J A P; van Engelshoven, Jos M A; Leiner, Tim; Kooi, Marianne E

    2009-03-01

    To investigate the potential of gadofosveset for contrast material-enhanced magnetic resonance (MR) imaging of plaque in a rabbit model of atherosclerosis. All experiments were approved by the animal ethics committee. Thirty-one New Zealand White rabbits were included in one of four study groups: animals with atherosclerosis imaged with gadofosveset (n = 10) or gadopentetate dimeglumine (n = 7) and control animals imaged with gadofosveset (n = 7) or gadopentetate dimeglumine (n = 7). Aortic atherosclerosis was induced through endothelial denudation combined with a cholesterol-enriched diet. Control rabbits underwent a sham surgical procedure and received a regular diet. After 8 weeks, pre- and postcontrast T1-weighted MR images of the aortic vessel wall were acquired. Relative signal enhancement was determined with dedicated software. Statistical analysis was performed by using a generalized linear mixed model. Immunohistochemical staining with CD31 and albumin was used to assess microvessel density and the albumin content of the vascular wall. Group differences were analyzed by using a chi(2) test. Gadofosveset spatial distribution and content within the vessel wall were determined with proton-induced x-ray emission (PIXE) analysis. Postcontrast signal enhancement was significantly greater for atherosclerotic than for control animals imaged with gadofosveset (P = .022). Gadopentetate dimeglumine could not enable discrimination between normal and atherosclerotic vessel walls (P = .428). PIXE analysis showed higher amounts of gadopentetate dimeglumine than gadofosveset in both atherosclerotic and normal rabbit aortas. Immunohistochemical staining revealed the presence of albumin and increased microvessel density in the vascular walls of atherosclerotic rabbits. These results suggest that gadofosveset can be used to differentiate between atherosclerotic and normal rabbit vessel walls. http://radiology.rsnajnls.org/cgi/content/full/250/3/682/DC1. RSNA, 2009

  19. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K., E-mail: willmann@stanford.edu

    2015-09-15

    Highlights: • Ultrasound molecular imaging is a highly sensitive modality. • A clinical grade ultrasound contrast agent has entered first in human clinical trials. • Several new potential future clinical applications of ultrasound molecular imaging are being explored. - Abstract: Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  20. Label-free imaging immune cells and collagen in atherosclerosis with two-photon and second harmonic generation microscopy

    Directory of Open Access Journals (Sweden)

    Chunqiang Li

    2016-01-01

    Full Text Available Atherosclerosis has been recognized as a chronic inflammation disease, in which many types of cells participate in this process, including lymphocytes, macrophages, dendritic cells (DCs, mast cells, vascular smooth muscle cells (SMCs. Developments in imaging technology provide the capability to observe cellular and tissue components and their interactions. The knowledge of the functions of immune cells and their interactions with other cell and tissue components will facilitate our discovery of biomarkers in atherosclerosis and prediction of the risk factor of rupture-prone plaques. Nonlinear optical microscopy based on two-photon excited autofluorescence and second harmonic generation (SHG were developed to image mast cells, SMCs and collagen in plaque ex vivo using endogenous optical signals. Mast cells were imaged with two-photon tryptophan autofluorescence, SMCs were imaged with two-photon NADH autofluorescence, and collagen were imaged with SHG. This development paves the way for further study of mast cell degranulation, and the effects of mast cell derived mediators such as induced synthesis and activation of matrix metalloproteinases (MMPs which participate in the degradation of collagen.

  1. Toward intravascular morphological and biochemical imaging of atherosclerosis with optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIM) (Conference Presentation)

    Science.gov (United States)

    Chen, Xi; Kim, Wihan; Serafino, Michael; Walton, Brian; Jo, Javier A.; Applegate, Brian E.

    2017-02-01

    We have shown in an ex vivo human coronary artery study that the biochemical information derived from FLIM interpreted in the context of the morphological information from OCT enables a detailed classification of human coronary plaques associated with atherosclerosis. The identification of lipid-rich plaques prone to erosion or rupture and associated with sudden coronary events can impact current clinical practice as well as future development of targeted therapies for "vulnerable" plaques. In order to realize clinical translation of intravascular OCT/FLIM we have had to develop several key technologies. A multimodal catheter endoscope capable of delivering near UV excitation for FLIM and shortwave IR for OCT has been fabricated using a ball lens design with a double clad fiber. The OCT illumination and the FLIM excitation propogate down the inner core while the large outer multimode core captures the fluorescence emission. To enable intravascular pullback imaging with this endoscope we have developed an ultra-wideband fiber optic rotary joint using the same double clad fiber. The rotary joint is based on a lensless design where two cleaved fibers, one fixed and one rotating, are brought into close proximity but not touching. Using water as the lubricant enabled operation over the near UV-shortwave IR range. Transmission over this bandwidth has been measured to be near 100% at rotational frequencies up to 147 Hz. The entire system has been assembled and placed on a mobile cart suitable for cath lab based imaging. System development, performance, and early ex vivo imaging results will be discussed.

  2. Non-invasive imaging for subclinical coronary atherosclerosis in patients with peripheral artery disease

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Kjaer, Andreas; Hesse, Birger

    2014-01-01

    of subclinical coronary artery disease varies widely in patients with peripheral artery disease, it could include more than half of patients. No consensus exists to date on either the rationale for screening patients with peripheral artery disease for coronary atherosclerosis or the optimal algorithm and method......Patients with peripheral artery disease are at high risk of coronary artery disease. An increasing number of studies show that a large proportion of patients with peripheral artery disease have significant coronary atherosclerosis, even in the absence of symptoms. Although the reported prevalence...

  3. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  4. Inorganic Nanoparticles for Multimodal Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Swierczewska

    2011-01-01

    Full Text Available Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle-based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles.

  5. Recent development of nanoparticles for molecular imaging

    Science.gov (United States)

    Kim, Jonghoon; Lee, Nohyun; Hyeon, Taeghwan

    2017-10-01

    Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  6. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Jin [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wang, Ying [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Su, Ke [Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Liu, Min [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Hu, Peng-Chao [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Ma, Tian; Li, Jia-Xi [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wei, Lei [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zheng, Zhongliang, E-mail: biochem@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Fang, E-mail: fang-yang@whu.edu.cn [Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.

  7. Is atherosclerosis imaging the most sensitive way to assess patients' risk and the best way to conduct future drug trials? A pros-and-cons debate.

    Science.gov (United States)

    Nanchen, David; Raggi, Paolo

    2017-11-01

    Atherosclerosis imaging has been the focus of intense debate and research for several decades. Among its primary applications are risk stratification of asymptomatic individuals and follow-up of atherosclerosis progression under a variety of treatments designed to retard or regress the development of arterial disease. Although endorsed and supported by many, this approach has been fiercely opposed by several key opinion leaders over the years. Similarly, regulatory agencies have raised a number of objections to resist the approval of new drugs and devices based on surrogate imaging markers. However, there is a large body of evidence in the medical literature that shows that risk stratification is improved with implementation of atherosclerosis imaging. Additionally, numerous lipid-modifying agents have been tested as far as their ability to affect progression of atherosclerosis, and in many cases the information obtained with imaging was in line with the outcome of subsequent clinical trials. This pros-and-cons debate was staged to bring up in a fun and provoking way the main arguments in favour or against the application of atherosclerosis imaging in the main settings described above. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Anatomical and molecular imaging of skin cancer

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-10-01

    Full Text Available Hao Hong1, Jiangtao Sun1, Weibo Cai1,21Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin – Madison, Madison, Wisconsin, USA; 2University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USAAbstract: Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼5% and nonmelanoma (∼95%, which can be further categorized into basal cell carcinoma, squamous cell carcinoma, and some rare skin cancer types. Biopsy is still the gold standard for skin cancer evaluation in the clinic. Various anatomical imaging techniques have been used to evaluate different types of skin cancer lesions, including laser scanning confocal microscopy, optical coherence tomography, high-frequency ultrasound, terahertz pulsed imaging, magnetic resonance imaging, and some other recently developed techniques such as photoacoustic microscopy. However, anatomical imaging alone may not be sufficient in guiding skin cancer diagnosis and therapy. Over the last decade, various molecular imaging techniques (in particular single photon emission computed tomography and positron emission tomography have been investigated for skin cancer imaging. The pathways or molecular targets that have been studied include glucose metabolism, integrin αvβ3, melanocortin-1 receptor, high molecular weight melanoma-associated antigen, and several other molecular markers. Preclinical molecular imaging is thriving all over the world, while clinical molecular imaging has not lived up to the expectations because of slow bench-to-bedside translation. It is likely that this situation will change in the near future and molecular imaging will truly play an important role in personalized medicine of melanoma patients.Keywords: skin cancer, molecular imaging, melanoma, anatomical imaging, positron emission tomography, antibody

  9. Molecular mechanisms of irbesartan suppressing atherosclerosis in high cholesterol-diet apolipoprotein E knock-out mice.

    Science.gov (United States)

    Yao, Rui; Cheng, Xiang; Chen, Yong; Xie, Jiang-Jiao; Yu, Xian; Liao, Meng-Yang; Ding, Ying-Jun; Tang, Ting-Ting; Liao, Yu-Hua

    2010-03-04

    Atherosclerosis is a chronic inflammatory disease in which the renin-angiotensin-aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of an angiotensin type 1 receptor blocker irbesartan on atherogenesis in high cholesterol-diet apolipoprotein E knock-out mice. Adult male apolipoprotein E knock-out mice were given normal diet or high cholesterol-diet and randomized to receive no treatment or irbesartan 10 mg kg(-1) d(-1) for 12 weeks. The apolipoprotein E knock-out mice with high cholesterol-diet were associated with a marked increase in atherosclerotic lesion area, plasma lipid and angiotensin II levels, as well as the expressions of angiotensin type 1 receptor in the aorta. High cholesterol-diet feeding increases the activity of NADPH oxidase subunits (p47(phox) and Rac), extracellular signal-regulated kinase 1/2, janus kinase 2, signal transducer and activator of transcription 3, nuclear factor-kappaB and the expression of tumor necrosis factor-alpha, interleukin 6, monocyte chemoattactant protein-1 and vascular cell adhesion molecule-1 in the aortas. These changes were suppressed in mice that were treated with irbesartan 10 mg kg(-1) d(-1), with no significant change in systolic blood pressure and plasma lipid levels. The results suggest that irbesartan can attenuate atherosclerosis, and this effect is partly related to the inhibition of oxidative stress and inflammatory signal transduction pathways which eventually leads to the decrease in the expression of inflammatory cytokines. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

  10. Preclinical molecular imaging using PET and MRI.

    Science.gov (United States)

    Wolf, Gunter; Abolmaali, Nasreddin

    2013-01-01

    Molecular imaging fundamentally changes the way we look at cancer. Imaging paradigms are now shifting away from classical morphological measures towards the assessment of functional, metabolic, cellular, and molecular information in vivo. Interdisciplinary driven developments of imaging methodology and probe molecules utilizing animal models of human cancers have enhanced our ability to non-invasively characterize neoplastic tissue and follow anti-cancer treatments. Preclinical molecular imaging offers a whole palette of excellent methodology to choose from. We will focus on positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques, since they provide excellent and complementary molecular imaging capabilities and bear high potential for clinical translation. Prerequisites and consequences of using animal models as surrogates of human cancers in preclinical molecular imaging are outlined. We present physical principles, values and limitations of PET and MRI as molecular imaging modalities and comment on their high potential to non-invasively assess information on hypoxia, angiogenesis, apoptosis, gene expression, metabolism, and cell trafficking in preclinical cancer research.

  11. Ultrasound Molecular Imaging: Moving Towards Clinical Translation

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.

    2015-01-01

    Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. PMID:25851932

  12. Ultrasound molecular imaging: Moving toward clinical translation.

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K

    2015-09-01

    Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Molecular imaging of apoptosis in cardiovascular diseases; Molekulare Bildgebung der Apoptose bei kardiovaskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, I.; Greschus, S.; Willinek, W.; Lohmaier, S.; Block, W.; Traeber, F.; Schild, H. [Bonn Univ. (Germany). Radiologische Universitaetsklinik; Heverhagen, J.T. [Marburg Univ. (Germany). Klinik fuer Strahlendiagnostik; Behe, M. [Marburg Univ. (Germany). Klinik fuer Nuklearmedizin; Wilhelm, K. [Radiologische Universitaetsklinik Bonn (Germany). FE Chirurgie

    2007-08-15

    Molecular imaging of functional parameters such as apoptosis (programmed cell death) in vivo opens new possibilities in clinical diagnostic and scientific research. Especially in the case of cardiovascular diseases that are mainly responsible for both morbidity and mortality in Western industrial nations, innovative non-invasive examination strategies are necessary for early diagnosis of these diseases. Since apoptosis unlike necrosis is present even after minor alterations of the microenvironment of cells and has been shown to be involved in a large number of cardiovascular diseases, there are currently several experimental studies underway with the goal of imaging apoptosis in vivo. The review discusses the basics of apoptosis in myocardial infarction, myocarditis, atherosclerosis, restenosis after angioplasty and stent implantation, currently used imaging techniques, achieved results, and future possibilities for molecular imaging of apoptosis. (orig.)

  14. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing

  15. Molecular Imaging of Urogenital Diseases

    OpenAIRE

    Cho, Steve Y.; Szabo, Zsolt; Morgan, Russell H.

    2014-01-01

    There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutics options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional computed tomography (CT) and bone scan (BS) is becoming increasingly important for...

  16. "Molecular" MR imaging at high fields.

    Science.gov (United States)

    Gore, John C; Zu, Zhongliang; Wang, Ping; Li, Hua; Xu, Junzhong; Dortch, Richard; Gochberg, Daniel F

    2017-05-01

    Magnetic resonance imaging (MRI) and spectroscopy (MRS) have contributed considerably to clinical radiology, and a variety of MR techniques have been developed to evaluate pathological processes as well as normal tissue biology at the cellular and molecular level. However, in comparison to nuclear imaging, MRI has relatively poor sensitivity for detecting true molecular changes or for detecting the presence of targeted contrast agents, though these remain under active development. In recent years very high field (7T and above) MRI systems have been developed for human studies and these provide new opportunities and technical challenges for molecular imaging. We identify 5 types of intrinsic contrast mechanisms that do not require the use of exogenous agents but which can provide molecular and cellular information. We can derive information on tissue composition by (i) imaging different nuclei, especially sodium (ii) exploiting chemical shift differences as in MRS (iii) exploiting specific relaxation mechanisms (iv) exploiting tissue differences in the exchange rates of molecular species such as amides or hydroxyls and (v) differences in susceptibility. The increased signal strength at higher fields enables higher resolution images to be acquired, along with increased sensitivity to detecting subtle effects caused by molecular changes in tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Molecular Imaging Probe Development using Microfluidics

    Science.gov (United States)

    Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

    2012-01-01

    In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

  18. Molecular and functional imaging of internet addiction.

    Science.gov (United States)

    Zhu, Yunqi; Zhang, Hong; Tian, Mei

    2015-01-01

    Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition.

  19. Has molecular imaging delivered to drug development?

    Science.gov (United States)

    Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

    2017-10-01

    Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  20. Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Kim, Won Yong; Astrup, Anne Sofie; Stuber, Matthias

    2007-01-01

    BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic...... cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden......, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; Pcoronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P

  1. Principles and basic concepts of molecular imaging.

    Science.gov (United States)

    Grenier, Nicolas; Brader, Peter

    2011-02-01

    Advanced knowledge in molecular biology and new technological developments in imaging modalities and contrast agents calls for molecular imaging (MI) to play a major role in the near future in many human diseases (Weissleder and Mahmood Radiology 219:316-333, 2001). Imaging systems are providing higher signal-to-noise ratio and higher spatial and/or temporal resolution. New specific contrast agents offer the opportunity to drive new challenges for obtaining functional and biological information on tissue characteristics and tissue processes. All this information could be relevant for diagnosis, prognosis and treatment follow-up and to drive local therapies, enhancing local drug/gene delivery. The recent explosion of all these developments is a radical change of perspective in our imaging community because they could have a tremendous impact on our clinical practice and on teaching programs and they call for a more prominent multidisciplinary approach in this field of research.

  2. Use of B-mode ultrasound to examine preclinical markers of atherosclerosis: image quality may bias associations between adiposity and measures of vascular structure and function.

    Science.gov (United States)

    Magnussen, Costan G; Thomson, Russell; Juonala, Markus; Viikari, Jorma S A; Dwyer, Terence; Raitakari, Olli T; Venn, Alison

    2011-03-01

    The purpose of this study was to examine the association between adiposity measures, ultrasound image quality, and preclinical markers of atherosclerosis in young adults. B-mode ultrasound was used to obtain common carotid intima-media thickness and common carotid artery distensibility of 2265 and 1313 adults aged 24 to 39 years in two population-based studies: the Cardiovascular Risk in Young Finns and Childhood Determinants of Adult Health studies. Qualitative assessments of ultrasound image quality were obtained from each study (scored as 1, excellent; 2, average; and 3, poor) based on the ability to detect arterial interfaces and the amount of noise present in the image. Increased adiposity was associated with significantly increased odds (all P media thickness in Young Finns (regression coefficient = -0.029; P = .01) and higher intima-media thickness in Childhood Determinants of Adult Health (regression coefficient = 0.013; P = .03) and lower distensibility levels in both studies (Young Finns, β = -.494; P bias) in the association between adiposity measures and carotid intima-media thickness by image quality, but there was some evidence suggesting that the association between adiposity measures and carotid distensibility differed by image quality. Adiposity affects ultrasound image quality and has the potential to bias associations between adiposity and preclinical markers of atherosclerosis. Studies examining adiposity and ultrasound-derived measures of atherosclerosis should consider taking steps during the design and analysis phase to adequately account for variations in image quality to avoid any potential bias.

  3. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  4. Molecular Probes for Fluorescence Lifetime Imaging

    Science.gov (United States)

    Sarder, Pinaki; Maji, Dolonchampa; Achilefu, Samuel

    2015-01-01

    Visualization of biological processes and pathologic conditions at the cellular and tissue levels largely rely on the use of fluorescence intensity signals from fluorophores or their bioconjugates. To overcome the concentration dependency of intensity measurements, evaluate subtle molecular interactions, and determine biochemical status of intracellular or extracellular microenvironments, fluorescence lifetime (FLT) imaging has emerged as a reliable imaging method complementary to intensity measurements. Driven by a wide variety of dyes exhibiting stable or environment-responsive FLTs, information multiplexing can be readily accomplished without the need for ratiometric spectral imaging. With knowledge of the fluorescent states of the molecules, it is entirely possible to predict the functional status of biomolecules or microevironment of cells. Whereas the use of FLT spectroscopy and microscopy in biological studies is now well established, in vivo imaging of biological processes based on FLT imaging techniques is still evolving. This review summarizes recent advances in the application of the FLT of molecular probes for imaging cells and small animal models of human diseases. It also highlights some challenges that continue to limit the full realization of the potential of using FLT molecular probes to address diverse biological problems, and outlines areas of potential high impact in the future. PMID:25961514

  5. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.

    Science.gov (United States)

    Borow, Kenneth M; Nelson, John R; Mason, R Preston

    2015-09-01

    Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. Serial Coronary Imaging of Early Atherosclerosis Development in Fast-Food-Fed Diabetic and Nondiabetic Swine

    Directory of Open Access Journals (Sweden)

    Nienke S. van Ditzhuijzen, MSc

    2016-10-01

    Full Text Available Patients with diabetes mellitus (DM are at increased risk for atherosclerosis-related events compared to non-DM (NDM patients. With an expected worldwide epidemic of DM, early detection of anatomic and functional coronary atherosclerotic changes is gaining attention. To improve our understanding of early atherosclerosis development, we studied a swine model that gradually developed coronary atherosclerosis. Interestingly, optical coherence tomography, near-infrared spectroscopy (NIRS, vascular function, and histology demonstrated no differences between development of early atherosclerosis in fast-food-fed (FF DM swine and that in FF-NDM swine. Coronary computed tomography angiography did not detect early atherosclerosis, but optical coherence tomography and near-infrared spectroscopy demonstrated coronary atherosclerosis development in FF-DM and FF-NDM swine.

  7. Molecular imaging: what can be used today

    NARCIS (Netherlands)

    Jager, P L; de Korte, M A; Lub-de Hooge, M N; van Waarde, A; Koopmans, K P; Perik, P J; de Vries, Liesbeth

    2005-01-01

    Biochemical cellular targets and more general metabolic processes in cancer cells can be visualised. Extensive data are available on molecular imaging in preclinical models. However, innovative tracers move slowly to the clinic. This review provides information on the currently available methods of

  8. Molecular Imaging in Nanotechnology and Theranostics.

    Science.gov (United States)

    Andreou, Chrysafis; Pal, Suchetan; Rotter, Lara; Yang, Jiang; Kircher, Moritz F

    2017-06-01

    The fields of biomedical nanotechnology and theranostics have enjoyed exponential growth in recent years. The "Molecular Imaging in Nanotechnology and Theranostics" (MINT) Interest Group of the World Molecular Imaging Society (WMIS) was created in order to provide a more organized and focused forum on these topics within the WMIS and at the World Molecular Imaging Conference (WMIC). The interest group was founded in 2015 and was officially inaugurated during the 2016 WMIC. The overarching goal of MINT is to bring together the many scientists who work on molecular imaging approaches using nanotechnology and those that work on theranostic agents. MINT therefore represents scientists, labs, and institutes that are very diverse in their scientific backgrounds and areas of expertise, reflecting the wide array of materials and approaches that drive these fields. In this short review, we attempt to provide a condensed overview over some of the key areas covered by MINT. Given the breadth of the fields and the given space constraints, we have limited the coverage to the realm of nanoconstructs, although theranostics is certainly not limited to this domain. We will also focus only on the most recent developments of the last 3-5 years, in order to provide the reader with an intuition of what is "in the pipeline" and has potential for clinical translation in the near future.

  9. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

    Levi, Jelena; Kothapalli, Sri-Rajashekar; Bohndiek, Sarah

    2013-01-01

    in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual wavelength imaging method. Results Active forms of both MMP2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent......Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers...... for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections...

  10. Solid silica nanoparticles: applications in molecular imaging.

    Science.gov (United States)

    Shirshahi, Vahid; Soltani, Madjid

    2015-01-01

    Silica and silica-based nanoparticles have been widely used for therapeutic and diagnostic applications in cancer mainly through delivery of drugs, genes and contrast agents. Development of synthesis methods has provided the possibility of fabricating silica nanoparticles with different sizes in nanometer ranges as well as silica-based multimodal nanoparticles with many innovative properties and intriguing applications in biomedicine. The surface of silica particles facilitates different methods of surface modifications and allows conjugation of various biomolecules such as proteins and nucleic acids. In this review, different methods of fabrication of silica and silica-based nanoparticles, their surface modification and the application of these nanoparticles in molecular imaging are discussed. Overall, the aim of this review is to address the development of silica and silica-based multifunctional nanoparticles that are introduced mainly for molecular imaging applications using optical, magnetic (MRI), X-ray (computed tomography) and multimodal imaging techniques. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Design and Synthesis of Gold Nanoparticle Contrast Agents for Atherosclerosis Imaging with Computed tomography

    Science.gov (United States)

    Chhour, Peter

    Cell tracking offers the opportunity to study migration and localization of cells in vivo, allowing investigations of disease mechanisms and drug efficacy. Monocytes play a key role in the progression of atherosclerotic plaques in the coronary arteries. While x-ray computed tomography (CT) is commonly used to clinically assess coronary plaque burden, cell tracking with CT is mostly unexplored. The establishment of monocyte cell tracking tools would allow for the direct investigation of gene and drug therapies aimed at monocyte recruitment in atherosclerosis. In this thesis, we present the design and optimization of gold nanoparticles as CT contrast agents for cell tracking of monocyte recruitment to atherosclerotic plaques. Gold nanoparticle polymer constructs with controlled localization are evaluated as potential monocyte labels. However, cytotoxic effects were observed at concentrations necessary for cell labeling. Therefore, variations in physical and chemical properties of gold nanoparticles were explored as cell labels for monocyte tracking. Each formulation was screened for effects on cell viability, cell function and uptake in monocytes. The uptake in monocytes revealed a complex relationship with nanoparticle size behavior dependent on the surface ligand used. This led to the selection of an optimal size and coating for monocyte labeling, 11-mercaptoundecanoic acid coated 15 nm gold nanoparticles. This formulation was further investigated for cell viability, function, and uptake with isolated primary monocytes. Moreover, primary monocytes labeled with this formulation were used to observe monocyte recruitment in atherosclerotic mice. Mice with early atherosclerotic plaques received intravenously injections of gold labeled monocytes and their recruitment to plaques were observed over 5 days with CT. Increases in CT attenuation in the plaque and transmission electron microscopy of plaque sections indicated the presence of gold labeled monocytes in the plaque

  12. Molecular optical imaging with radioactive probes.

    Directory of Open Access Journals (Sweden)

    Hongguang Liu

    Full Text Available BACKGROUND: Optical imaging (OI techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI. METHODOLOGY/PRINCIPAL FINDINGS: By taking the advantages of low energy window of light (1.2-3.1 eV, 400-1000 nm resulting from radiation, radionuclides that emit charged particles such as beta(+ and beta(- can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2-[(18F]fluoro-D-glucose ([(18F]FDG, Na(18F, Na(131I, (90YCl(3 and a (90Y labeled peptide that specifically target tumors. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate generalizability of radioactive OI technique. It provides a new molecular imaging strategy and will likely have significant impact on both small animal and clinical imaging.

  13. Three Dimensional Molecular Imaging for Lignocellulosic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W.; Sweedler, Jonathan V.

    2011-06-09

    The development of high efficiency, inexpensive processing protocols to render biomass components into fermentable substrates for the sequential processing of cell wall components into fuels and important feedstocks for the biorefinery of the future is a key goal of the national roadmap for renewable energy. Furthermore, the development of such protocols depends critically on detailed knowledge of the spatial and temporal infiltration of reagents designed to remove and separate the phenylpropenoid heteropolymer (lignin) from the processable sugar components sequestered in the rigid cell walls of plants. A detailed chemical and structural understanding of this pre-enzymatic processing in space and time was the focus of this program. We worked to develop new imaging strategies that produce real-time molecular speciation information in situ; extract sub-surface information about the effects of processing; and follow the spatial and temporal characteristics of the molecular species in the matrix and correlate this complex profile with saccharification. Spatially correlated SIMS and Raman imaging were used to provide high quality, high resolution subcellular images of Miscanthus cross sections. Furthermore, the combination of information from the mass spectrometry and Raman scattering allows specific chemical assignments of observed structures, difficult to assign from either imaging approach alone and lays the foundation for subsequent heterocorrelated imaging experiments targeted at more challenging biological systems, such as the interacting plant-microbe systems relevant to the rhizosphere.

  14. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Science.gov (United States)

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

  15. Molecular Photoacoustic Imaging of Follicular Thyroid Carcinoma

    Science.gov (United States)

    Levi, Jelena; Kothapalli, Sri-Rajashekar; Bohndiek, Sarah; Yoon, Joon-Kee; Dragulescu-Andrasi, Anca; Nielsen, Carsten; Tisma, Aleksandra; Bodapati, Sunil; Gowrishankar, Gayatri; Yan, Xinrui; Chan, Carmel; Starcevic, Daniela; Gambhir, Sanjiv Sam

    2013-01-01

    Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual wavelength imaging method. Results Active forms of both MMP2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, non-activatable, agent. Conclusions With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas. PMID:23349314

  16. Atherosclerosis imaging using 3D black blood TSE SPACE vs 2D TSE.

    Science.gov (United States)

    Wong, Stephanie K; Mobolaji-Iawal, Motunrayo; Arama, Leron; Cambe, Joy; Biso, Sylvia; Alie, Nadia; Fayad, Zahi A; Mani, Venkatesh

    2014-05-28

    To compare 3D Black Blood turbo spin echo (TSE) sampling perfection with application-optimized contrast using different flip angle evolution (SPACE) vs 2D TSE in evaluating atherosclerotic plaques in multiple vascular territories. The carotid, aortic, and femoral arterial walls of 16 patients at risk for cardiovascular or atherosclerotic disease were studied using both 3D black blood magnetic resonance imaging SPACE and conventional 2D multi-contrast TSE sequences using a consolidated imaging approach in the same imaging session. Qualitative and quantitative analyses were performed on the images. Agreement of morphometric measurements between the two imaging sequences was assessed using a two-sample t-test, calculation of the intra-class correlation coefficient and by the method of linear regression and Bland-Altman analyses. No statistically significant qualitative differences were found between the 3D SPACE and 2D TSE techniques for images of the carotids and aorta. For images of the femoral arteries, however, there were statistically significant differences in all four qualitative scores between the two techniques. Using the current approach, 3D SPACE is suboptimal for femoral imaging. However, this may be due to coils not being optimized for femoral imaging. Quantitatively, in our study, higher mean total vessel area measurements for the 3D SPACE technique across all three vascular beds were observed. No significant differences in lumen area for both the right and left carotids were observed between the two techniques. Overall, a significant-correlation existed between measures obtained between the two approaches. Qualitative and quantitative measurements between 3D SPACE and 2D TSE techniques are comparable. 3D-SPACE may be a feasible approach in the evaluation of cardiovascular patients.

  17. Molecular Imaging System for Monitoring Tumor Angiogenesis

    Science.gov (United States)

    Aytac, Esra; Burcin Unlu, Mehmet

    2012-02-01

    In cancer, non-invasive imaging techniques that monitor molecular processes associated with the tumor angiogenesis could have a central role in the evaluation of novel antiangiogenic and proangiogenic therapies as well as early detection of the disease. Matrix metalloproteinases (MMP) can serve as specific biological targets for imaging of angiogenesis since expression of MMPs is required for angiogenesis and has been found to be upregulated in every type of human cancer and correlates with stage, invasive, metastatic properties and poor prognosis. However, for most cancers it is still unknown when, where and how MMPs are involved in the tumor angiogenesis [1]. Development of high-resolution, high sensitivity imaging techniques in parallel with the tumor models could prove invaluable for assessing the physical location and the time frame of MMP enzymatic acitivity. The goal of this study is to understand where, when and how MMPs are involved in the tumor angiogenesis. We will accomplish this goal by following two objectives: to develop a high sensitivity, high resolution molecular imaging system, to develop a virtual tumor simulator that can predict the physical location and the time frame of the MMP activity. In order to achieve our objectives, we will first develop a PAM system and develop a mathematical tumor model in which the quantitative data obtained from the PAM can be integrated. So, this work will develop a virtual tumor simulator and a molecular imaging system for monitoring tumor angiogenesis. 1.Kessenbrock, K., V. Plaks, and Z. Werb, MMP:regulators of the tumor microenvironment. Cell, 2010. 141(1)

  18. Obesity, Insulin Resistance, and Incident Small Vessel Disease on Magnetic Resonance Imaging: Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    Dearborn, Jennifer L; Schneider, Andrea L C; Sharrett, A Richey; Mosley, Thomas H; Bezerra, Daniel C; Knopman, David S; Selvin, Elizabeth; Jack, Clifford R; Coker, Laura H; Alonso, Alvaro; Wagenknecht, Lynne E; Windham, Beverly G; Gottesman, Rebecca F

    2015-11-01

    The term metabolic syndrome describes the clustering of risk factors found in many individuals with obesity. Because of their pathophysiology, we hypothesized that 2 features of metabolic syndrome, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on magnetic resonance imaging, and specifically with incident lacunar disease and not white matter hyperintensity (WMH) progression. Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study, who completed 2 brain magnetic resonance imagings≈10 years apart. WMH progression and incident lacunes between the 2 magnetic resonance imagings were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, homeostatic model assessment-IR, body mass index, and waist circumference. Metabolic syndrome (presence/absence), using standard clinical definitions, and IR score at the first magnetic resonance imaging, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 versus Q1-Q4) and incident lacunes. Metabolic syndrome (adjusted odds ratio, 1.98; 95% confidence interval, 1.28-3.05) and IR score (adjusted odds ratio per 1-SD increase, 1.33; 95% confidence interval, 1.05-1.68) were associated with incident lacunes but not with WMH progression. Insulin, homeostatic model assessment-IR, and body mass index were not associated with incident lacunes or WMH progression in separate models. The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease. © 2015 American Heart Association, Inc.

  19. Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-06-01

    Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

  20. Molecular Breast Imaging Using Emission Tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Gopan, O. [University of Florida; Gilland, D. [University of Florida; Weisenberger, Andrew G. [JLAB; Kross, Brian J. [JLAB; Welch, Benjamin L. [Dilon Technologies

    2013-06-01

    Purpose: Tour objective is to design a novel SPECT system for molecular breast imaging (MBI) and evaluate its performance. The limited angle SPECT system, or emission tomosynthesis, is designed to achieve 3D images of the breast with high spatial resolution/sensitivity. The system uses a simplified detector motion and is conducive to on-board biopsy and mult-modal imaging with mammography. Methods: The novel feature of the proposed gamma camera is a variable-angle, slant-hole (VASH) collimator, which is well suited for limited angle SPECT of a mildly compressed breast. The collimator holes change slant angle while the camera surface remains flush against the compression paddle. This allows the camera to vary the angular view ({+-}30{degrees}, {+-}45{degrees}) for tomographic imaging while keeping the camera close to the object for high spatial resolution and/or sensitivity. Theoretical analysis and Monte Carlo simulations were performed assuming a point source and isolated breast phantom. Spatial resolution, sensitivity, contrast and SNR were measured. Results were compared to single-view, planar images and conventional SPECT. For both conventional SPECT and VASH, data were reconstructed using iterative algorithms. Finally, a proof-of-concept VASH collimator was constructed for experimental evaluation. Results: Measured spatial resolution/sensitivity with VASH showed good agreement with theory including depth-of-interaction (DOI) effects. The DOI effect diminished the depth resolution by approximately 2 mm. Increasing the slant angle range from {+-}30{degrees} to {+-}45{degrees} resulted in an approximately 1 mm improvement in the depth resolution. In the breast phantom images, VASH showed improved contrast and SNR over conventional SPECT and improved contrast over planar scintimmammography. Reconstructed images from the proof-of-concept VASH collimator demonstrated reasonable depth resolution capabilities using limited angle projection data. Conclusion: We

  1. Molecular imaging in Libman-Sacks endocarditis

    DEFF Research Database (Denmark)

    Dahl, Anders; Schaadt, Bente K; Santoni-Rugiu, Eric

    2015-01-01

    cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult...... to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, (18)F-FDG-PET-CT clearly...

  2. Molecular imaging of autism spectrum disorder.

    Science.gov (United States)

    Hwang, Brian Jaeho; Mohamed, Mona Adel; Brašić, James Robert

    2017-12-01

    Autism spectrum disorder (ASD) is a condition with onset in early childhood characterized by marked deficits in interpersonal interactions and communication and by a restricted and repetitive range of interests and activities. This review points out key recent findings utilizing molecular imaging including magnetic resonance spectroscopy (MRS) and nuclear neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). MRS indicates an excitatory/inhibitory imbalance in high-functioning autism. Dysfunction of neurotransmitter and glucose metabolism has been demonstrated by PET and SPECT. Levels of serotonin synthesis in typically developing children are approximately twice those of adults; after the age of 5 years, levels decrease to those of adults. In contrast, levels of serotonin synthesis of children with ASD increase between ages 2 and 15 to 1.5-times adult values. The dopamine transporter is increased in the orbitofrontal cortex of men with ASD. The serotonin transporter is reduced in the brains of children, adolescents, and adults with ASD. Reduced serotonin receptors in the thalamus of adults with ASD are associated with communication difficulties. Glucose metabolism is reduced in the brains of people with ASD. Molecular imaging will provide the preliminary data for promising therapeutic interventions.

  3. Recent advances in the development of PET/SPECT probes for atherosclerosis imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Yoich; Kuge, Yuji [Hokkaido University, Sapporo (Japan)

    2016-12-15

    The rupture of vulnerable atherosclerotic plaques and subsequent thrombus formation are the major causes of myocardial and cerebral infarction. Accordingly, the detection of vulnerable plaques is important for risk stratification and to provide appropriate treatment. Inflammation imaging using 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ({sup 18}F-FDG) has been most extensively studied for detecting vulnerable atherosclerotic plaques. It is of great importance to develop PET/SPECT probes capable of specifically visualizing the biological molecules involved in atherosclerotic plaque formation and/or progression. In this article, we review recent advances in the development of PET/SPECT probes for visualizing atherosclerotic plaques and their application to therapy monitoring, mainly focusing on experimental studies.

  4. Multimodality molecular imaging of disease progression in living ...

    Indian Academy of Sciences (India)

    imaging techniques, (ii) radionuclide-based positron emission tomography (PET) and single photon emitted computed tomography (SPECT), (iii) X-ray-based computed tomography (CT), (iv) magnetic resonance imaging. (MRI) and (v) ultrasound imaging (US). Functional molecular imaging requires an imaging probe that is ...

  5. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  6. Manganese G8 dendrimers targeted to oxidation-specific epitopes: in vivo MR imaging of atherosclerosis.

    Science.gov (United States)

    Nguyen, Tuyen H; Bryant, Henry; Shapsa, Ari; Street, Hannah; Mani, Venkatesh; Fayad, Zahi A; Frank, Joseph A; Tsimikas, Sotirios; Briley-Saebo, Karen C

    2015-03-01

    To determine if manganese (Mn) G8 dendrimers targeted to oxidation-specific epitopes (OSE) allow for in vivo detection of atherosclerotic lesions. OSE have been identified as key factors in atherosclerotic plaque progression and destabilization. Mn offers a potentially clinically translatable alternative to gadolinium-based agents when bioretention and potential toxicity of gadolinium is anticipated. However, to be effective, high payloads of Mn must accumulate intracellularly in macrophages. It was hypothesized that G8 dendrimers targeted to OSE may allow delivery of high Mn payloads, thereby enabling in vivo detection of macrophage-rich plaques. G8 dendrimers were modified to allow conjugation with MnDTPA (758 Mn ion) and the antibody MDA2 that is targeted to malondialdehyde (MDA)-lysine epitopes. Both the untargeted and targeted G8 dendrimers were characterized and their in vivo efficacy evaluated in apoE(-/-) mice over a 96-hour time period after bolus administration of a 0.05 mmol Mn/kg dose using a clinical MR system (3T). Significant enhancement (normalized enhancement >60%, P = 0.0013) of atherosclerotic lesions was observed within a 72-hour time period following administration of the targeted dendrimers. The presence of Mn within atherosclerotic lesions was confirmed using spectroscopic methods (>8 μg Mn/g). Limited signal attenuation (<18%) and Mn deposition (<1 μg Mn/g) was observed in the arterial wall following injection of the untargeted material. This study demonstrates that manganese-labeled dendrimers, allowing a high Mn payload, targeted to OSE may allow in vivo image of atherosclerotic lesions. © 2014 Wiley Periodicals, Inc.

  7. Molecular Imaging of Stem Cell Transplantation in Myocardial Disease

    OpenAIRE

    Chung, Jaehoon; Yang, Phillip C.

    2010-01-01

    Stem cell therapy has been heralded as a novel therapeutic option for cardiovascular disease. In vivo molecular imaging has emerged as an indispensible tool in investigating stem cell biology post-transplantation into the myocardium and in evaluating the therapeutic efficacy. This review highlights the features of each molecular imaging modality and discusses how these modalities have been applied to evaluate stem cell therapy.

  8. Molecular Theranostics: A Primer for the Imaging Professional

    Science.gov (United States)

    Lee, Daniel Y.; Li, King C. P.

    2012-01-01

    OBJECTIVE A theranostic system integrates some form of diagnostic testing to determine the presence of a molecular target for which a specific drug is intended. Molecular imaging serves this diagnostic function and provides powerful means for noninvasively detecting disease. We briefly review the paradigms rooted in nuclear medicine and highlight recent advances in this field. We also explore how nanometersized complexes, called nanomedicines, present an excellent theranostic platform applicable to both drug discovery and clinical use. CONCLUSION For imagers, molecular theranostics represents a powerful emerging platform that intimately couples targeted therapeatic entities with noninvasive imaging that yields information on the presence of defined molecular targets before, during, and after cognate therapy. PMID:21785076

  9. Molecular Imaging and Precision Medicine in Prostate Cancer.

    Science.gov (United States)

    Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

    2017-01-01

    The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Intravital Microscopy for Atherosclerosis Research

    NARCIS (Netherlands)

    Megens, Remco T. A.; Soehnlein, Oliver

    2015-01-01

    Recruitment of leukocytes into arteries is a hallmark event throughout all stages of atherosclerosis and hence stands out as a primary therapeutic target. To understand the molecular mechanisms of arterial leukocyte subset infiltration, real-time visualization of recruitment processes of leukocyte

  11. Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis.

    Science.gov (United States)

    Ma, Sheng-Chao; Zhang, Hui-Ping; Kong, Fan-Qi; Zhang, Hui; Yang, Cheng; He, Yang-Yang; Wang, Yan-Hua; Yang, An-Ning; Tian, Ju; Yang, Xiao-Ling; Zhang, Ming-Hao; Xu, Hua; Jiang, Yi-Deng; Yu, Zheng

    2016-06-01

    The aim of the present study was to identify an effective method for detecting early‑phase atherosclerosis (AS), as well as to provide useful DNA methylation profiles to serve as biomarkers for the detection of AS. A total of 300 individuals (150 AS patients and 150 healthy subjects) were recruited for peripheral blood DNA methylation analyses at 12 gene promoter loci using nested methylation‑specific polymerase chain reaction in a test set. Based on the test set, the promoter methylation of TIMP metallopeptidase inhibitor 1 (TIMP1), ATP binding cassette subfamily A member 1 (ABCA1), and acetyl-CoA acetyltransferase 1 (ACAT1) were determined to be candidate biomarkers; demonstrating the highest sensitivity (88%) and specificity (90%). The biomarkers that were candidates for early AS detection were validated in an independent validation set (n=100). In the validation set, the combination of TIMP1, ABCA1 and ACAT1 methylation achieved sensitivity, specificity and coincidence rate values of 88, 70 and 79%, respectively. In the current pilot study, the patterns of DNA methylation of AS‑associated genes were observed to be significantly altered in the peripheral blood of AS patients. Thus, the AS-specific methylation of the three‑gene panel (TIMP1, ABCA1, and ACAT1) may serve as a valuable biomarker for the early detection of AS.

  12. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2009-03-01

    Full Text Available Prostate cancer is the most common malignancy in men and continues to be a major public health problem. Imaging of prostate cancer remains particularly challenging owing to disease heterogeneity. Molecular imaging can provide unprecedented opportunities for deciphering the molecular mechanisms that are involved in the development and natural progression of prostate cancer from a localized process to the hormone-refractory metastatic disease. Such understanding will be the key for targeted imaging and therapy and for predicting and evaluating treatment response and prognosis. In this article, we review briefly the contribution of multimodality molecular imaging methods for the in vivo characterization of the pathophysiology of prostate cancer.

  13. Molecular Imaging with Single-Walled Carbon Nanotubes

    Science.gov (United States)

    Hong, Hao; Gao, Ting; Cai, Weibo

    2011-01-01

    Nanoparticle-based molecular imaging has emerged as an interdisciplinary field which involves physics, chemistry, engineering, biology, and medicine. Single-walled carbon nanotubes (SWCNTs) have unique properties which make them suitable for applications in a variety of imaging modalities, such as magnetic resonance, near-infrared fluorescence, Raman spectroscopy, photoacoustic tomography, and radionuclide-based imaging. In this review, we will summarize the current state-of-the-art of SWCNTs in molecular imaging applications. Multifunctionality is the key advantage of nanoparticles over traditional approaches. Targeting ligands, imaging labels, therapeutic drugs, and many other agents can all be integrated into the nanoparticle to allow for targeted molecular imaging and molecular therapy by encompassing many biological and biophysical barriers. A multifunctional, SWCNT-based nanoplatform holds great potential for clinical applications in the future. PMID:21754949

  14. Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

    Science.gov (United States)

    Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

    2017-03-01

    Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

  15. Cellular and Molecular Imaging Using Chemical Exchange Saturation Transfer.

    Science.gov (United States)

    McMahon, Michael T; Gilad, Assaf A

    2016-10-01

    Chemical exchange saturation transfer (CEST) is a powerful new tool well suited for molecular imaging. This technology enables the detection of low concentration probes through selective labeling of rapidly exchanging protons or other spins on the probes. In this review, we will highlight the unique features of CEST imaging technology and describe the different types of CEST agents that are suited for molecular imaging studies, including CEST theranostic agents, CEST reporter genes, and CEST environmental sensors.

  16. Computational methods in molecular imaging technologies

    CERN Document Server

    Gunjan, Vinit Kumar; Venkatesh, C; Amarnath, M

    2017-01-01

    This book highlights the experimental investigations that have been carried out on magnetic resonance imaging and computed tomography (MRI & CT) images using state-of-the-art Computational Image processing techniques, and tabulates the statistical values wherever necessary. In a very simple and straightforward way, it explains how image processing methods are used to improve the quality of medical images and facilitate analysis. It offers a valuable resource for researchers, engineers, medical doctors and bioinformatics experts alike.

  17. Resonance Energy Transfer Molecular Imaging Application in Biomedicine

    Directory of Open Access Journals (Sweden)

    NIE Da-hong1,2;TANG Gang-hua1,3

    2016-11-01

    Full Text Available Resonance energy transfer molecular imaging (RETI can markedly improve signal intensity and tissue penetrating capacity of optical imaging, and have huge potential application in the deep-tissue optical imaging in vivo. Resonance energy transfer (RET is an energy transition from the donor to an acceptor that is in close proximity, including non-radiative resonance energy transfer and radiative resonance energy transfer. RETI is an optical imaging technology that is based on RET. RETI mainly contains fluorescence resonance energy transfer imaging (FRETI, bioluminescence resonance energy transfer imaging (BRETI, chemiluminescence resonance energy transfer imaging (CRETI, and radiative resonance energy transfer imaging (RRETI. RETI is the hot field of molecular imaging research and has been widely used in the fields of biology and medicine. This review mainly focuses on RETI principle and application in biomedicine.

  18. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

    2009-05-15

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  19. Luminescence imaging using radionuclides: a potential application in molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Chan [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Il An, Gwang [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Park, Se-Il [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Oh, Jungmin [Korea Basic Science Institute Chuncheon Center, Gangwon-do 200-701 (Korea, Republic of); Kim, Hong Joo [Department of Physics and Energy Science, Kyungpook National University, Daegu 702-710 (Korea, Republic of); Su Ha, Yeong; Wang, Eun Kyung [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Min Kim, Kyeong; Kim, Jung Young [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jaetae [Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Welch, Michael J. [Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Yoo, Jeongsoo, E-mail: yooj@knu.ac.k [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2011-04-15

    Introduction: Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. Methods: The luminescence intensities of various radionuclides having different decay modes have been assayed using luminescence imaging and in vitro luminometer. Radioiodinated Herceptin was injected into a tumor-bearing mouse, and luminescence and microPET images were obtained. The plant dipped in [{sup 32}P]phosphate solution was scanned in luminescence mode. Radio-TLC plate was also imaged in the same imaging mode. Results: Radionuclides emitting high energy {beta}{sup +}/{beta}{sup -} particles showed higher luminescence signals. NIH3T6.7 tumors were detected in both optical and nuclear imaging. The uptake of [{sup 32}P]phosphate in plant was easily followed by luminescence imaging. Radio-TLC plate was visualized and radiochemical purity was quantified using luminescence imaging. Conclusion: Many radionuclides with high energetic {beta}{sup +} or {beta}{sup -} particles during decay were found to be imaged in luminescence mode due mainly to Cerenkov radiation. 'Cerenkov imaging' provides a new optical imaging platform and an invaluable bridge between optical and nuclear imaging. New optical imaging probes could be easily prepared using well-established radioiodination methods. Cerenkov imaging will have more applications in the research field of plant science and autoradiography.

  20. Iron oxide nanoparticle-micelles (ION-micelles for sensitive (molecular magnetic particle imaging and magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Lucas W E Starmans

    Full Text Available BACKGROUND: Iron oxide nanoparticles (IONs are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. METHODS AND RESULTS: IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles. Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles bound to blood clots. CONCLUSIONS: The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular MPI and warrants further investigation of the Fib

  1. Quantification of the focal progression of coronary atherosclerosis through automated co-registration of virtual histology-intravascular ultrasound imaging data.

    Science.gov (United States)

    Timmins, Lucas H; Molony, David S; Eshtehardi, Parham; Rasoul-Arzrumly, Emad; Lam, Adrian; Hung, Olivia Y; McDaniel, Michael C; Oshinski, John N; Giddens, Don P; Samady, Habib

    2017-01-01

    The goal of this study was to evaluate the accuracy of a novel algorithm that circumferentially co-registers serial virtual histology-intravascular ultrasound (VH-IVUS) data for the focal assessment of coronary atherosclerosis progression. Thirty-three patients with an abnormal non-invasive cardiac stress test or stable angina underwent baseline and follow-up (6 or 12 months) invasive evaluation that included acquisition of VH-IVUS image data. Baseline and follow-up image pairs (n = 4194) were automatically co-registered in the circumferential direction via a multi-variate cross-correlation algorithm. Algorithm stability and accuracy were assessed by comparing results from multiple iterations of the algorithm (iteration 1 vs. iteration 2) and against values determined manually by two expert VH-IVUS readers (algorithm vs. two expert readers). Furthermore, focal plaque progression values were compared between the algorithm and expert readers following co-registration by the independently determined angles. Strong agreement in circumferential co-registration angles were observed across multiple iterations of the algorithm (stability) and between the algorithm and expert readers (accuracy; all concordance correlation coefficients >0.98). Furthermore, circumferential co-registration angles determined by the algorithm were not statistically when compared to values determined by two expert readers (p = 0. 99). Bland-Altman analysis indicated minimal bias when comparing focal VH-IVUS defined plaque progression in corresponding sectors following circumferential co-registration between the algorithm and expert readers. Finally, average differences in changes in total plaque and constituent areas between the algorithm and readers were within the average range of difference between readers (interobserver variability). We present a stable and validated algorithm to automatically circumferentially co-register serial VH-IVUS imaging data for the focal quantification of

  2. Contrast-enhanced ultrasound for molecular imaging of angiogenesis.

    Science.gov (United States)

    Eisenbrey, J R; Forsberg, F

    2010-08-01

    Molecular imaging of angiogenesis using contrast-enhanced ultrasound allows for functional, real-time, inexpensive imaging of angiogenesis. The addition of stabilized microbubbles as contrast agents greatly improves ultrasound signal to noise ratio/signal strength/image quality (up to 25 dB) and allows for imaging of angiogenic vasculature. In this article recent advances in the usage of contrast-enhanced ultrasound for molecular imaging of angiogenesis are reviewed. The usage of commercially available agents and correlations between their imaging parameters and molecular markers of angiogenesis are reviewed. Recent developments in ultrasound contrast agents targeted to angiogenic markers for both diagnosis and monitoring are discussed. Finally, a brief overview of the emerging field of chemotherapeutic-loaded agents, which can be used with ultrasound-triggered drug delivery, is provided.

  3. Quantitative Methods for Molecular Diagnostic and Therapeutic Imaging

    OpenAIRE

    Li, Quanzheng

    2013-01-01

    This theme issue provides an overview on the basic quantitative methods, an in-depth discussion on the cutting-edge quantitative analysis approaches as well as their applications for both static and dynamic molecular diagnostic and therapeutic imaging.

  4. Molecular Imaging and Radiotherapy: Theranostics for Personalized Patient Management

    OpenAIRE

    Irina Velikyan

    2012-01-01

    This theme issue presents current achievements in the development of radioactive agents, pre-clinical and clinical molecular imaging, and radiotherapy in the context of theranostics in the field of oncology.

  5. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers

  6. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging

    NARCIS (Netherlands)

    Ciccarelli, O.; Barkhof, F.; Bodini, B.; De Stefano, N.; Golay, X.; Nicolay, K; Pelletier, D.; Pouwels, P.J.W.; Smith, S.A.; Wheeler-Kingshott, C.A.M.; Stankoff, B.; Yousry, T.; Miller, D. H.

    2014-01-01

    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many

  7. Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

    Directory of Open Access Journals (Sweden)

    Fangfang Chao

    2013-01-01

    Full Text Available Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB, in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI, nuclear medicine imaging, and optical imaging (OI. Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke.

  8. Glycoconjugate probes and targets for molecular imaging using magnetic resonance

    NARCIS (Netherlands)

    Geraldes, C.F.G.C.; Djanashvili, K.; Peters, J.A.

    2010-01-01

    Recently, many research activities in medical diagnosis have been devoted to molecular imaging with MRI. A key issue is the evaluation of molecular targets that allow the early detection and characterization of diseases and the assessment of the effects of therapy. The majority of the current

  9. Atherosclerosis and Stroke

    Science.gov (United States)

    ... Inspirational Stories Stroke Heroes Among Us Atherosclerosis and Stroke Updated:Oct 24,2016 Excerpted and adapted from " ... it can cause difficulty walking and eventually gangrene. Stroke and atherosclerosis There are two types of ischemic ...

  10. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase, the receptor on the cells (e.g., transferrin receptor, and endogenous reporter genes (e.g., ferritin reporter gene. However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies.

  11. Natural language processing and visualization in the molecular imaging domain.

    Science.gov (United States)

    Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

    2007-06-01

    Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

  12. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...... for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm...

  13. Applications of molecular MRI and optical imaging in cancer.

    Science.gov (United States)

    Penet, Marie-France; Mikhaylova, Maria; Li, Cong; Krishnamachary, Balaji; Glunde, Kristine; Pathak, Arvind P; Bhujwalla, Zaver M

    2010-06-01

    Some of the most exciting advances in molecular-functional imaging of cancer are occurring at the interface between chemistry and imaging. Several of these advances have occurred through the development of novel imaging probes that report on molecular pathways, the tumor micro-environment and the response of tumors to treatment; as well as through novel image-guided platforms such as nanoparticles and nanovesicles that deliver therapeutic agents against specific targets and pathways. Cancer cells have a remarkable ability to evade destruction despite the armamentarium of drugs currently available. While these drugs can destroy cancer cells, normal tissue toxicity is a major limiting factor, a problem further compounded by poor drug delivery. One major challenge for chemistry continues to be to eliminate cancer cells without damaging normal tissues. Here we have selected examples of MRI and optical imaging, to demonstrate how integrating imaging with novel probes can facilitate the successful treatment of this multifaceted disease.

  14. Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

    2011-09-15

    Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

  15. Chemistry and engineering of cyclodextrins for molecular imaging.

    Science.gov (United States)

    Lai, Wing-Fu; Rogach, Andrey L; Wong, Wing-Tak

    2017-10-16

    Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides bearing a basket-shaped topology with an "inner-outer" amphiphilic character. The abundance of hydroxyl groups enables CDs to be functionalized with multiple targeting ligands and imaging elements. The imaging time, and the payload of different imaging elements, can be tuned by taking advantage of the commercial availability of CDs with different sizes of the cavity. This review aims to offer an outlook of the chemistry and engineering of CDs for the development of molecular probes. Complexation thermodynamics of CDs, and the corresponding implications for probe design, are also presented with examples demonstrating the structural and physiochemical roles played by CDs in the full ambit of molecular imaging. We hope that this review not only offers a synopsis of the current development of CD-based molecular probes, but can also facilitate translation of the incremental advancements from the laboratory to real biomedical applications by illuminating opportunities and challenges for future research.

  16. The Role of Molecular Imaging in Drug Delivery.

    Science.gov (United States)

    Niu, Gang; Chen, Xiaoyuan

    The parallel development of molecular imaging and drug delivery allows the combination of therapeutic agents with imaging moieties, which facilitates visualisation of the drug delivery process and provides a realtime readout on the in vivo efficacy of a therapeutic agent. Although challenging, it is feasible to construct a highly versatile, multifunctional single 'theranostic' probe for quantitative molecular imaging, targeted drug delivery and controlled drug release to obtain an effective therapeutic response. Compared with conventional methods for the evaluation of pharmacokinetics/pharmacodynamics, molecular imaging has advantages such as substantially decreasing the workload and increasing the volume of more precise data with statistical relevance. More importantly, molecular imaging techniques bridge the gap between pre-clinical and clinical research to develop candidate drugs that have the optimal target specificity, pharmacodynamics and efficacy. With the advancement and integration of technology in various fields, diverse types of targeted imaging probe coupled with drug delivery potential have been developed. Preliminary data have demonstrated that it is feasible and promising to use these targeted carriers for simultaneous target imaging and drug delivery.

  17. Vaccination to Modulate Atherosclerosis

    Science.gov (United States)

    Kimura, Takayuki; Tse, Kevin; Sette, Alessandro; Ley, Klaus

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of the artery wall. Adaptive immunity plays a key role in the pathogenesis of atherosclerosis. Recently, modulation of the immune response against atherosclerotic plaque antigen(s) has attracted attention as a potentially preventive and therapeutic approach. Here we review a series of studies on immunization with various antigens targeting treatment and prevention of atherosclerosis. Atherosclerosis-related antigens include oxidized LDL, apolipoprotein B-100, and heat shock protein 60/65. Accumulating evidence supports the idea that immunization with these antigenic proteins or peptides may reduce atherosclerosis. In this review, we discuss the current status of immunization studies and possible associated mechanisms of atheroprotection. PMID:25683179

  18. Thermoacoustic Molecular Imaging of Small Animals

    Directory of Open Access Journals (Sweden)

    Robert A. Kruger

    2003-04-01

    Full Text Available We have designed, constructed, and tested a thermoacoustic computed tomography (TCT scanner for imaging optical absorption in small animals in three dimensions. The device utilizes pulsed laser irradiation (680–1064 nm and a unique, 128-element transducer array. We quantified the isotropic spatial resolution of this scanner to be 0.35 mm. We describe a dual-wavelength subtraction technique for isolating optical dyes with TCT. Phantom experiments demonstrate that we can detect 5 fmol of a near-infrared dye (indocyanine green, ICG in a 1-ML volume using dual-wavelength subtraction. Initial TCT imaging in phantoms and in two sacrificed mice suggests that three-dimensional, optical absorption patterns in small animals can be detected with an order of magnitude better spatial resolution and an order of magnitude better low-contrast detectability in small animals when compared to fluorescence imaging or diffusion optical tomography.

  19. Molecular breast imaging. An update; Molekulare Brustbildgebung. Ein Update

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, K.; Helbich, T.H.; Magometschnigg, H.; Baltzer, P. [Medizinische Universitaet Wien, Abteilung fuer Molekulare Bildgebung, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Fueger, B. [Medizinische Universitaet Wien, Abteilung fuer Molekulare Bildgebung, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Medizinische Universitaet Wien, Abteilung fuer Nuklearmedizin, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

    2014-03-15

    The aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging. Currently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy ({sup 1}H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI). Recently, novel techniques for molecular imaging of breast tumors, such as sodium imaging ({sup 23}Na-MRI), phosphorus spectroscopy ({sup 31}P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation. It can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible. (orig.) [German] Die molekulare Bildgebung zielt auf die Darstellung, Beschreibung und Quantifizierung biologischer, physiologischer und pathologischer Prozesse auf zellulaerer und molekularer Ebene ab. In den letzten Jahren hat sich die molekulare Bildgebung mit ihren verschiedenen Modalitaeten in der Brustdiagnostik etabliert. Die molekularen Brustbildgebung umfasst derzeit die multiparametrische(MP)-MRT mit funktioneller und morphologischer kontrastmittelverstaerkter MRT (KM-MRT), molekularer diffusionsgewichteter Bildgebung (''diffusion-weighted imaging'', DWI) und metabolischer Protonenspektroskopie ({sup 1}H-MRSI) sowie nuklearmedizinische Verfahren (brustspezifische Gammakamerabildgebung [BSGI], Positronenemissionstomographie [PET], PET

  20. Imaging with MCP in molecular beam experiments

    CERN Document Server

    Rodionov, I; Shilov, I

    2001-01-01

    The main goal of the fast molecular beam experiments is the measurement of differential cross sections of the most actual gas-phase reactions within a wide range of translational energies of reagents. For setting up such experiments the R and D Center 'Reagent' scientific group designed a series of particle and photon detectors. By way of complexity and historically these detectors place as follows:(1) 0D--one element scanning detectors; (2) 2D-position-sensitive detectors (PSD) based on microchannel plate; (3) 2D+T-time and position-sensitive detectors (TPSD); (4) 2D+2D+delta T-Multiparticle position-sensitive detectors (MTPSD); (5) 2D+T-the fluorescent photon TPSD with photocathodes. We report the development of the methods for particles and photons detection in the fast molecular beam experiments. The results of measurements on the basis of such detectors are also considered.

  1. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  2. Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

    Directory of Open Access Journals (Sweden)

    Jinhui Li

    2017-01-01

    Full Text Available The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted 99mTc-, 123I-, and 18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.

  3. Data on atherosclerosis specific antibody conjugation to nanoemulsions

    Directory of Open Access Journals (Sweden)

    Geoffrey Prévot

    2017-12-01

    Full Text Available This article present data related to the publication entitled “Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging” (Prévot et al., 2017 [1]. Herein we describe the engineering in the baculovirus-insect cell system and purification processes of the human scFv-Fc TEG4-2C antibody, specific of platelets within the atheroma plaque. For molecular targeting purpose, atheroma specific antibody was conjugated to nanoemulsions (NEs using a heterobifunctional linker (DSPE-PEG-maleimide. Atheroma labelling was assayed by immunochemistry on arterial sections from rabbits.

  4. Molecular Imaging of Breast Cancer: Role of RGD Peptides.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  5. Molecular Imaging of Ovarian Carcinoma Angiogenesis

    Science.gov (United States)

    2007-03-01

    competition curve was then fitted by the Hill equation (GraphPad). A representative autoradiogram of a competition experiment for A549 tumor is...tomography imaging of vascular endothelial growth factor receptor expression. J Nucl Med. In press 2006. 27. Goncalves M, Estieu-Gionnet K, Berthelot T, et al...muscle ( Equation 1). The ratio of integrated tumor uptake divided by tumor uptake was set as the y-axis. The ratio of integrated reference tissue

  6. Hybrid image potential states in molecular overlayers on graphene

    Science.gov (United States)

    Wella, Sasfan Arman; Sawada, Hiroyuki; Kawaguchi, Nana; Muttaqien, Fahdzi; Inagaki, Kouji; Hamada, Ikutaro; Morikawa, Yoshitada; Hamamoto, Yuji

    2017-11-01

    The structural and electronic properties of naphthalene adsorbed on graphene are studied from first principles using the van der Waals density functional method. It is shown that naphthalene molecules are stabilized by forming a superstructure with the periodicity of (2 √{3 }×2 √{3 }) and a tilted molecular adsorption geometry on graphene, in good agreement with the scanning tunneling microscopy (STM) experiments on highly oriented pyrolytic graphite. Our results predict that image potential states (IPSs) are induced by intermolecular interaction on the naphthalene overlayer, hybridizing with the IPSs derived from graphene. The resultant hybrid IPSs are characterized by anisotropic effective mass reflecting the molecular structure of naphthalene. By means of STM simulations, we reveal that one of the hybrid IPSs manifests itself as an oval protrusion distinguishable from naphthalene molecular orbitals, which identifies the origin of an experimental STM image previously attributed to the lowest unoccupied molecular orbital of naphthalene.

  7. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  8. Molecular imaging using sodium iodide symporter (NIS)

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Je Yoel [School of Dentistry, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-04-01

    Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice xenografted with human melanoma, glioma, breast cancer of prostate cancer, rats with subcutaneous thyroid tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition, the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a therapeutic requires a more efficient and specific system of gene delivery with better retention of radioiodide in tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a therapeutic strategy for a variety of human diseases.

  9. Molecular imaging with dynamic contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K.A., E-mail: k.a.miles@bsms.ac.u [Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton (United Kingdom)

    2010-07-15

    Dynamic contrast-enhanced computed tomography (DCE-CT) is a quantitative technique that employs rapid sequences of CT images after bolus administration of intravenous contrast material to measure a range of physiological processes related to the microvasculature of tissues. By combining knowledge of the molecular processes underlying changes in vascular physiology with an understanding of the relationship between vascular physiology and CT contrast enhancement, DCE-CT can be redefined as a molecular imaging technique. Some DCE-CT derived parameters reflect tissue hypoxia and can, therefore, provide information about the cellular microenvironment. DCE-CT can also depict physiological processes, such as vasodilatation, that represent the physiological consequences of molecular responses to tissue hypoxia. To date the main applications have been in stroke and oncology. Unlike some other molecular imaging approaches, DCE-CT benefits from wide availability and ease of application along with the use of contrast materials and software packages that have achieved full regulatory approval. Hence, DCE-CT represents a molecular imaging technique that is applicable in clinical practice today.

  10. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  11. MIPortal: A High Capacity Server for Molecular Imaging Research

    Directory of Open Access Journals (Sweden)

    Misha Pivovarov

    2005-10-01

    Full Text Available The introduction of novel molecular tools in research and clinical medicine has created a need for more refined information management systems. This article describes the design and implementation of such a new information platform: the Molecular Imaging Portal (MIPortal. The platform was created to organize, archive, and rapidly retrieve large datasets using Web-based browsers as access points. The system has been implemented in a heterogeneous, academic research environment serving Macintosh, Unix, and Microsoft Windows clients and has been shown to be extraordinarily robust and versatile. In addition, it has served as a useful tool for clinical trials and collaborative multi-institutional small-animal imaging research.

  12. Molecular endoscopy for targeted imaging in the digestive tract.

    Science.gov (United States)

    Lee, Jeong Hoon; Wang, Thomas D

    2016-10-01

    Endoscopy uses optical imaging methods to investigate tissue in a non-destructive manner with high resolution over a broad range of wavelengths, thus providing a powerful tool to rapidly visualise mucosal surfaces in the digestive tract. Molecular imaging is an important advancement that has been clinically demonstrated for early cancer detection and guidance of therapy. With this approach, imaging can be used to observe expression patterns of molecular targets to improve understanding of key biological mechanisms that drive disease progression. Prototype devices that collect fluorescence for wide-field or microscopic images have been developed. Several targeting moieties, including enzyme-activatable probes, antibodies, peptides, and lectins, have been administered in preclinical and clinical imaging studies in vivo. These emerging technologies provide useful approaches to study molecular events in different signalling pathways, producing insights that could lead to improved interventions to prevent and treat gastrointestinal diseases. In this Review, we introduce the basic concepts that form the foundation for development of molecular endoscopy and summarise key results from preclinical and clinical studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Molecular imaging in cardiovascular diseases; Molekulare kardiovaskulaere MRT-Bildgebung

    Energy Technology Data Exchange (ETDEWEB)

    Botnar, R.M. [King' s College London (United Kingdom). Imaging Sciences; St. Thomas' NHS Foundation Trust, London (United Kingdom); Ebersberger, H. [Heart Center Munich-Bogenhausen, Munich (Germany). Dept. of Cardiology and Intensive Care Medicine; Noerenberg, D. [Charite, Berlin (Germany). Inst. for Radiology; and others

    2015-02-15

    Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

  14. Photoacoustic molecular imaging of ferritin as a reporter gene

    Science.gov (United States)

    Ha, S.; Carson, A.; Kim, K.

    2012-02-01

    Spectral analysis of photoacoustic (PA) molecular imaging (PMI) of ferritin expressed in human melanoma cells (SK-24) was performed in vitro. Ferritin is a ubiquitously expressed protein which stores iron that can be detected by PA imaging, allowing ferritin to act as a reporter gene. To over-express ferritin, SK-24 cells were co-transfected with plasmid expressing Heavy chain ferritin (H-FT) and plasmid expressing enhanced green fluorescent protein (pEGFP-C1) using LipofectamineTM 2000. Non-transfected SK-24 cells served as a negative control. Fluorescent imaging of EGFP confirmed transfection and transgene expression in co-transfected cells. To detect iron accumulation in SK-24 cells, a focused high frequency ultrasonic transducer (60 MHz, f/1.5), synchronized to a pulsed laser (molecular imaging and basic science research.

  15. Molecular Imaging with Small Animal PET/CT

    DEFF Research Database (Denmark)

    Binderup, T.; El-Ali, H.H.; Skovgaard, D.

    2011-01-01

    Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However...... in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements...... is also described. In addition, the non-invasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small...

  16. White blood cell count is associated with carotid and femoral atherosclerosis

    NARCIS (Netherlands)

    Ortega, Emilio; Gilabert, Rosa; Nuñez, Isabel; Cofán, Montserrat; Sala-Vila, Aleix; de Groot, Eric; Ros, Emili

    2012-01-01

    Objective: Chronic low-grade inflammation is associated with atherosclerosis. Ultrasound imaging allows measurement of intima-media thickness (IMT) and plaque. We investigated the association between inflammatory markers and carotid and femoral atherosclerosis. Methods: We studied 554 subjects with

  17. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S. [Oak Ridge National Laboratory; Endres, Christopher J. [Johns Hopkins, Baltimore; Foss, Catherine A. [Johns Hopkins, Baltimore; Nimmagadda, Sridhar [Johns Hopkins, Baltimore; Jung, Hyeyun [Johns Hopkins, Baltimore; Goddard, James S. [Oak Ridge National Laboratory; Lee, Seung Joon [JLAB; McKisson, John [JLAB; Smith, Mark F. [University of Maryland; Stolin, Alexander V. [West Virginia University; Weisenberger, Andrew G. [JLAB; Pomper, Martin G. [Johns Hopkins, Baltimore

    2013-06-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  18. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S [ORNL; Endres, Christopher [Johns Hopkins University; Foss, Catherine [Johns Hopkins University; Nimmagadda, Sridhar [Johns Hopkins University; Jung, Hyeyun [Johns Hopkins University; Goddard Jr, James Samuel [ORNL; Lee, Seung Joon [Jefferson Lab; McKisson, John [Jefferson Lab; Smith, Mark F. [University of Maryland School of Medicine, The, Baltimore, MD; Stolin, Alexander [West Virginia University, Morgantown; Weisenberger, Andrew G. [Jefferson Lab; Pomper, Martin [Johns Hopkins University

    2013-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  19. Dendrimer-based contrast agents for molecular imaging.

    Science.gov (United States)

    Longmire, Michelle; Choyke, Peter L; Kobayashi, Hisataka

    2008-01-01

    The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging.

  20. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-{alpha}, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with {sup 99m}Tc or {sup 111}In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for

  1. Inflammasomes and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    S. Vallurupalli, MD

    2016-09-01

    Full Text Available Inflammation plays an important role in atherosclerosis. Inflammasomes play a crucial role in innate immunity, which mediates the body’s response to various pathogens. Of the different types of inflammasomes, NLRP3 has been implicated in atherosclerosis through the production of proinflammatory cytokines, IL-1β and IL-18. This review describes the role of the NLRP3 inflammasome in atherosclerosis and discusses potential therapeutic targets in the inflammasome pathway.

  2. Intraoperative Molecular Imaging for Rapid Assessment of Tumor Margins

    Science.gov (United States)

    2011-09-01

    approach in animal models using a the MRI- FMT imaging system (Task 5). A description of the primary accomplishments and ongoing efforts follows...guided fluorescence molecular tomography ( FMT ) of ( ) ( ) ( ) tBP k NTNTT etCBP kRktCRtC + − ∗    + ++= 12121 2 1 9 two fluorescent probes in...administration, mice were imaged for an hour at approximately two minutes per frame using an MR-coupled FMT system. The imaging system is a spectrometer

  3. Toward Molecular Imaging-Driven Drug Development in Oncology

    NARCIS (Netherlands)

    de Vries, Elisabeth G. E.; Munnink, Thijs H. Oude; van Vugt, Marcel A. T. M.; Nagengast, Wouter B.

    With current testing strategies, the number of novel targeted anticancer agents will exceed our drug selection capacity. Molecular imaging is a powerful additional tool that can assist us in selecting effective drugs and help patients benefit from targeted agents. Moreover, measurement of the

  4. Positron Emission Tomography Molecular Imaging in Late-Life Depression

    OpenAIRE

    Hirao, Kentaro; Smith, Gwenn S.

    2014-01-01

    Molecular imaging represents a bridge between basic and clinical neuroscience observations and provides many opportunities for translation and identifying mechanisms that may inform prevention and intervention strategies in late-life depression (LLD). Substantial advances in instrumentation and radiotracer chemistry have resulted in improved sensitivity and spatial resolution and the ability to study in vivo an increasing number of neurotransmitters, neuromodulators, and, importantly, neuropa...

  5. Application of molecular ultrasound for imaging integrin expression.

    Science.gov (United States)

    Kiessling, Fabian; Gaetjens, Jessica; Palmowski, Moritz

    2011-02-01

    Stabilized microbubbles with a size between 1-5 µm are used as ultrasound contrast agents in the clinical routine. They have shown convincing results for the vascular characterization of tissues as well as in echocardiography. Due to their size, microbubbles strictly remain intravascular where they can be detected with high sensitivity and specificity. This qualifies them for intravascular molecular imaging. Many studies have been published reporting on the successful use of microbubbles conjugated to specific ligands for target identification in vivo. Among them, there are several promising examples on how to use molecular ultrasound for the imaging of integrin expression. This review provides an overview on the composition of ultrasound contrast agents that can be used for molecular imaging and their detection by ultrasound using destructive and non destructive methods. Furthermore, concrete examples are given on the use of molecular ultrasound to characterize integrin expression on vessels. These cover oncological applications where integrin targeted microbubbles were used to identify and characterize tumor angiogenesis and to assess tumor response to antiangiogenic drugs as well as to radiotherapy. In addition, increased accumulation of integrin targeted microbubbles was found during vascular reformation in ischemic tissues as well as in vulnerable atherosclerotic plaques. In summary, there is clear evidence from preclinical studies that integrin targeted ultrasound imaging is a valuable tool for the characterization of a broad spectrum of diseases. Thus, more efforts should be put into translating this promising technology into the clinics.

  6. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2013-09-01

    for breast cancer specimens that involve microcalcifications or nonpalpable masses and does not occur for palpable breast masses (Cabioglu et al...John V Frangioni. 2008. “Detection of Breast Cancer Microcalcifications Using a Dual-modality SPECT/NIR Fluorescent Probe.” Journal of the American...Enabled Optical Molecular Imaging of Breast Cancer PRINCIPAL INVESTIGATOR: Rebekah Drezek, Ph.D

  7. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  8. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  9. Molecular Ultrasound Imaging for the Detection of Neural Inflammation

    Science.gov (United States)

    Volz, Kevin R.

    Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was

  10. Molecular Imaging of Apoptosis: From Micro to Macro

    Science.gov (United States)

    Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S.; Chen, Xiaoyuan

    2015-01-01

    Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. PMID:25825597

  11. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  12. Embryonic stem cell biology: insights from molecular imaging.

    Science.gov (United States)

    Sallam, Karim; Wu, Joseph C

    2010-01-01

    Embryonic stem (ES) cells have therapeutic potential in disorders of cellular loss such as myocardial infarction, type I diabetes and neurodegenerative disorders. ES cell biology in living subjects was largely poorly understood until incorporation of molecular imaging into the field. Reporter gene imaging works by integrating a reporter gene into ES cells and using a reporter probe to induce a signal detectable by normal imaging modalities. Reporter gene imaging allows for longitudinal tracking of ES cells within the same host for a prolonged period of time. This has advantages over postmortem immunohistochemistry and traditional imaging modalities. The advantages include expression of reporter gene is limited to viable cells, expression is conserved between generations of dividing cells, and expression can be linked to a specific population of cells. These advantages were especially useful in studying a dynamic cell population such as ES cells and proved useful in elucidating the biology of ES cells. Reporter gene imaging identified poor integration of differentiated ES cells transplanted into host tissue as well as delayed donor cell death as reasons for poor long-term survival in vivo. This imaging technology also confirmed that ES cells indeed have immunogenic properties that factor into cell survival and differentiation. Finally, reporter gene imaging improved our understanding of the neoplastic risk of undifferentiated ES cells in forming teratomas. Despite such advances, much remains to be understood about ES cell biology to translate this technology to the bedside, and reporter gene imaging will certainly play a key role in formulating this understanding.

  13. Angiotensin converting enzyme 2 and atherosclerosis.

    Science.gov (United States)

    Wang, Yutang; Tikellis, Chris; Thomas, Merlin C; Golledge, Jonathan

    2013-01-01

    Angiotensin converting enzyme 2 (ACE2) is a homolog of angiotensin converting enzyme (ACE) which generates angiotensin II from angiotensin I. ACE, its product angiotensin II and the downstream angiotensin type I receptor are important components of the renin-angiotensin system (RAS). Angiotensin II, the most important component of the RAS, promotes the development of atherosclerosis. The identification of ACE2 in 2000 opened a new chapter of research on the regulation of the RAS. ACE2 degrades pro-atherosclerotic angiotensin II and generates anti-atherosclerotic angiotensin 1-7. In this review, we explored the importance of ACE2 in protecting experimental animals from developing atherosclerosis and its involvement in human atherosclerosis. We also examined the published evidence assessing the importance of ACE2 in different cell types relevant to atherosclerosis and putative underlying cellular and molecular mechanisms linking ACE2 with protection from atherosclerosis. ACE2 shifts the balance from angiotensin II to angiotensin 1-7 inhibiting the progression of atherosclerosis in animal models. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Periodontal innate immune mechanisms relevant to atherosclerosis.

    Science.gov (United States)

    Amar, S; Engelke, M

    2015-06-01

    Atherosclerosis is a common cardiovascular disease in the USA where it is a leading cause of illness and death. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high-fat diet, obesity, high blood cholesterol levels, and smoking. However, a sizable number of patients suffering from atherosclerosis do not harbor the classical risk factors. Ongoing infections have been suggested to play a role in this process. Periodontal disease is perhaps the most common chronic infection in adults with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. This review focuses on exploring the molecular consequences of infection by pathogens that exacerbate atherosclerosis, with the focus on infections by the periodontal bacterium Porphyromonas gingivalis as a running example. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Vaccination against atherosclerosis

    NARCIS (Netherlands)

    Es, Thomas van

    2009-01-01

    Atherosclerosis, the predominantly underlying pathology of cardiovascular events, is the consequence of lipid deposition in the arterial wall, mostly as consequence of high levels of serum cholesterol. Treatment of atherosclerosis is mainly focused at the reduction of cholesterol levels by lipid

  16. MR molecular imaging of tumor vasculature and vascular targets.

    Science.gov (United States)

    Pathak, Arvind P; Penet, Marie-France; Bhujwalla, Zaver M

    2010-01-01

    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from "bench to bedside". The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  17. Molecular imaging and the neuropathologies of Parkinson's disease

    DEFF Research Database (Denmark)

    Cumming, Paul; Borghammer, Per

    2012-01-01

    The main motor symptoms of Parkinson's disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [(18)F]-fluoro-L-DOPA (FDOPA) and lig......The main motor symptoms of Parkinson's disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [(18)F]-fluoro-L-DOPA (FDOPA......) and ligands for DA transporter ligands. However, the pathologies of PD are by no means limited to nigrostriatal loss. Results of post mortem and molecular imaging studies reveal parallel degenerations of cortical noradrenaline (NA) and serotonin (5-HT) innervations, which may contribute to affective...... with denervation upregulation, but there is an accelerated rate of DA receptor loss as the disease advances. Animal studies and post mortem investigations reveal changes in brain opioid peptide systems, but these are poorly documented in imaging studies of PD. Relatively minor changes in the binding sites for GABA...

  18. Development of molecular imaging method for manitoring estrogen receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Jung, W. S.; Jung, J. G.; Kang, J. H.; Lee, Y. J.; Kim, K. I.; O, H. J.; Jung, J. M.; Lee, D. S.; Lee, M. C. [Seoul Nation University, Seoul (Korea, Republic of)

    2004-07-01

    Estrogen receptor is expressed in 50-60% of the breast cancer and hormone therapy is effective for only ER-positive breast cancer. Therefore, we need to know whether or not the ER is expressed in breast cancer before hormone therapy. So far, the method for monitoring ER positiveness in breast tissue is radioreceptor assay or immunohistochemistry which is invasive method due to tissue biopsy. In this study, we develop the molecular imaging method of sodium iodide symporter (NIS) gene as a reporter gene for monitoring ER activity. Because molecular imaging is evaluation method through the comparison between the image intensities obtained in vivo, molecular imaging method is noninvasive and easily quantitative. We constructed the recombinant plasmid (pERE-NIS) which NIS gene expression is controlled by estrogen response element (ERE) promoter. MCF-7, ER-expressing human breast cancer cell line, was transfected with pERE-NIS with lipofectamine (Invitrogen Co). When pERE-NIS transfected MCF-7 was treated with estradiol or tamoxifen, intracellular uptake of {sup 125}I was higher than those of non-treated. The activation of ERE by drug treatment was occurred and it was caused to expression of NIS gene. The degree of {sup 125}I uptake depend on treated drug concentration. However, in case of pERE-NIS transfected breast cancer which do not express ER, there was no response with drug treatment. Therefore, we can monitor ER functionality and the efficacy of drugs with this pERE-NIS reporter system.

  19. Molecular Imaging of VEGF Receptors in Graft Arteriosclerosis

    Science.gov (United States)

    Zhang, Jiasheng; Razavian, Mahmoud; Tavakoli, Sina; Nie, Lei; Tellides, George; Backer, Joseph M.; Backer, Marina V.; Bender, Jeffrey R.; Sadeghi, Mehran M.

    2012-01-01

    Objectives Vascular endothelial growth factor (VEGF) signaling plays a key role in the pathogenesis of vascular remodeling, including graft arteriosclerosis (GA). GA is the major cause of late organ failure in cardiac transplantation. We used molecular near-infrared fluorescent (NIRF) imaging with an engineered Cy5.5-labeled single-chain VEGF tracer (scVEGF/Cy) to detect VEGF receptors (VEGFRs) and vascular remodeling in human coronary artery grafts by molecular imaging. Methods and Results VEGFR-specificity of probe uptake was shown by flow cytometry in endothelial cells. In severe combined immunodeficiency mice, transplantation of human coronary artery segments into the aorta followed by adoptive transfer of allogeneic human peripheral blood mononuclear cells (PBMCs) led to significant neointima formation in the grafts over a period of 4 weeks. NIRF imaging of transplant recipients at 4 weeks demonstrated focal uptake of scVEGF/Cy in remodeling artery grafts. Uptake specificity was demonstrated using an inactive homologue of scVEGF/Cy. scVEGF/Cy uptake predominantly localized in the neointima of remodeling coronary arteries and correlated with VEGFR-1, but not VEGFR-2 expression. There was a significant correlation between scVEGF/Cy uptake and transplanted artery neointima area. Conclusions Molecular imaging of VEGF receptors may provide a non-invasive tool for detection of GA in solid organ transplantation. PMID:22723442

  20. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    Science.gov (United States)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  1. Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: the atherosclerosis risk in communities study.

    Science.gov (United States)

    Bryan, R N; Cai, J; Burke, G; Hutchinson, R G; Liao, D; Toole, J F; Dagher, A P; Cooper, L

    1999-08-01

    MR imaging has revealed putative evidence of subclinical cerebrovascular disease (CVD) as reflected by white matter signal changes and infarct-like lesions (ILLs). Nonetheless, the prevalence of this condition in the general population has been defined only to a limited extent. We herein report the prevalence and anatomic characteristics of ILLs seen on cranial MR images obtained as part of a population-based study of cardiovascular disease in middle-aged adults. These results are contrasted to those of previous similar studies, particularly those of an elderly population in the Cardiovascular Health Study (CHS). This Atherosclerosis Risk in Communities (ARIC) cohort consists of a probability sample of community-living persons who were 55 to 72 years old at the time of MR examination. MR imaging of 1890 participants was performed at two ARIC field centers, based on a common protocol. MR studies were evaluated by trained readers at the MR Reading Center using original digital data displayed on a high-resolution workstation. The measures of lesion size, anatomic location, and signal intensity were collected. The definition for an ILL was a non-mass, hyperintense region with an arterial vascular distribution on spin-density and T2-weighted images. Two hundred ninety participants had ILLs, for an overall prevalence of 15.3%. Eighty-two percent of participants with ILLs had lesions that were 3 mm or larger in maximal dimension, although 87% of these lesions were 20 mm or smaller in maximal dimension. The prevalence of ILLs increased with age, from 7.9% in the 55- to 59-year-old age group to 22.9% in the 65- to 72-year-old age group (P general population. Furthermore, the prevalence of this subclinical disease increases with age, and is greater in black persons. ILLs are dominated by "lacunae" in the basal ganglia and thalamus. These results are, in general, similar to those of a comparable study of elderly participants in the CHS, except for a 60% lower prevalence of

  2. Vasculitis: Molecular Imaging by Targeting the Inflammatory Enzyme Myeloperoxidase

    Science.gov (United States)

    Su, Henry S.; Nahrendorf, Matthias; Panizzi, Peter; Breckwoldt, Michael O.; Rodriguez, Elisenda; Iwamoto, Yoshiko; Aikawa, Elena; Weissleder, Ralph

    2012-01-01

    Purpose: To determine if a molecular imaging approach targeting the highly oxidative enzyme myeloperoxidase (MPO) can help noninvasively identify and confirm sites of vascular wall inflammation in a murine model of vasculitis. Materials and Methods: Animal experiments were approved by the institutional animal care committee. Twenty-six mice were studied, including eight MPO-deficient and six sham-operated mice as controls. Vasculitis was induced with intraperitoneal injection of Candida albicans water-soluble fraction (CAWS). Aortic root magnetic resonance imaging was performed after intravenous injection of the activatable MPO sensor (bis-5-hydroxytryptamide-diethylenetriaminepentatacetate gadolinium) (n = 23), referred to as MPO-Gd, or gadopentetate dimeglumine (n = 10). Seven mice were randomly assigned to receive either MPO-Gd or gadopentetate dimeglumine first. Aortic root specimens were collected for biochemical and histopathologic analyses to validate imaging findings. Statistical significance was calculated for contrast-to-noise ratios (CNRs) by using the paired t test. Results: In the aortic root, the mean MPO-Gd CNRs after agent injection (CNR = 28.1) were more than 2.5-fold higher than those of sham-operated mice imaged with MPO-Gd and vasculitis mice imaged with gadopentetate dimeglumine (CNR = 10.6) (P gadopentetate dimeglumine. Histopathologic and biochemical analyses for MPO and myeloid cells confirmed imaging findings. In MPO-deficient mice, injection of CAWS did not result in a vasculitis phenotype, implying a key role of the imaging target in disease cause. Conclusion: Molecular imaging targeting MPO can be a useful biomarker to noninvasively detect and confirm inflammation in vasculitis by using a murine model of Kawasaki disease. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110040/-/DC1 PMID:22084204

  3. The Application of Contrast Enhanced Ultrasound in Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jong; Chung, Jin Haeung; Hwang, Sung Il [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-09-15

    Microbubble contrast agent for ultrasound imaging has come of age, adding entirely new capabilities to real time ultrasound imaging. These new ultrasound imaging techniques exploit the nonlinear echoes that result from the unique interaction between ultrasound and microbubbles, which are readily distinguishable from the echoes of tissues. Contrast enhanced ultrasound can be used to quantify both flow rate and relative vascular volume of the microvasculature in solid lesions or organs, which makes it possible for it to be one of the modalities in molecular imaging. Angiogenesis is one of the important processes contributing to new blood vessel growth that occurs in a variety of physiologic and pathophysiologic states. It is essential for spread and growth of malignant tumors. The advantages of contrast enhanced ultrasound are that it is a noninvasive method for observing tumor angiogenesis. Sonoporation utilizes the interaction of ultrasound with ultrasound contrast agents to temporarily permeabilized the cell membrane allowing for the uptake of DNA, drugs, and other therapeutic compounds from the extracellular environment. Thus, sonoporation is a promising drug delivery and gene therapy technique, limited only by lack of understanding regarding the biophysical mechanism that results in the cell membrane permeability change. In conclusion, ultrasound contrast agent could have a role not only in the molecular imaging field with the advantage of noninvasive quantification of angiogenesis, but also in the field of drug treatment of cells using sonoporation

  4. Genetic Basis of Atherosclerosis: Insights from Mice and Humans

    Science.gov (United States)

    Stylianou, Ioannis M.; Bauer, Robert C.; Reilly, Muredach P.; Rader, Daniel J.

    2012-01-01

    Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have in part been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease (CAD). Here we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human CAD. Furthermore, we discuss in greater detail some of these novel human CAD loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches. PMID:22267839

  5. Imaging isodensity contours of molecular states with STM

    Science.gov (United States)

    Reecht, Gaël; Heinrich, Benjamin W.; Bulou, Hervé; Scheurer, Fabrice; Limot, Laurent; Schull, Guillaume

    2017-11-01

    We present an improved way for imaging the density of states of a sample with a scanning tunneling microscope, which consists in mapping the surface topography while keeping the differential conductance (dI/dV) constant. When archetypical C60 molecules on Cu(111) are imaged with this method, these so-called iso-dI/dV maps are in excellent agreement with theoretical simulations of the isodensity contours of the molecular orbitals. A direct visualization and unambiguous identification of superatomic C60 orbitals and their hybridization is then possible.

  6. Molecular imaging of retinal endothelial injury in diabetic animals

    Directory of Open Access Journals (Sweden)

    Sonja Frimmel

    2017-01-01

    Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.

  7. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    OpenAIRE

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow...

  8. The Center for Integrated Molecular Brain Imaging (Cimbi) database

    DEFF Research Database (Denmark)

    Knudsen, Gitte M.; Jensen, Peter S.; Erritzoe, David

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions rela...... currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank....

  9. Molecular imaging of proteins in tissues by mass spectrometry

    OpenAIRE

    Seeley, Erin H.; Caprioli, Richard M.

    2008-01-01

    Imaging MS (IMS) is an emerging technology that permits the direct analysis and determination of the distribution of molecules in tissue sections. Biological molecules such as proteins, peptides, lipids, xenobiotics, and metabolites can be analyzed in a high-throughput manner with molecular specificity not readily achievable through other means. Tissues are analyzed intact and thus spatial localization of molecules within a tissue is preserved. Several studies are presented that focus on the ...

  10. Towards risk stratification in systemic atherosclerosis: value of myocardial function and viability imaging as an adjunct to MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Seeger, Achim; Fenchel, Michael; Kramer, Ulrich; Bretschneider, Christiane; Grimm, Florian; Klumpp, Bernhard; Claussen, Claus D.; Miller, Stephan [Eberhard Karls University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Scheule, Albertus [Eberhard Karls University Tuebingen, Department for Thorax, Cardiac and Vascular Surgery, Tuebingen (Germany); Balletshofer, Bernd [Eberhard Karls University Tuebingen, Department of Internal Medicine IV, Tuebingen (Germany)

    2010-04-15

    To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease. Cardiac MRI was performed in 195 consecutive patients with symptomatic peripheral arterial disease. Of these, 186 patients were followed for 22 {+-} 5 months for the presence of cardiac events (cardiac death, acute coronary syndrome and hospitalisation as a result of congestive heart failure). Myocardial viability imaging showed a high prevalence of known (n = 31) and occult myocardial infarctions (MI) (n = 26). Cardiac events occurred more often in patients with reduced ventricular function (ejection fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40-55%, cardiac event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients) as well as in patients with occult MI (8/25 patients) and known MI (11/30 patients). In patients with normal function, the detection of a previous MI was of high relevance to prognosis. Both reduced EF and the presence of MI influence patients' prognoses. Performing cardiac MRI in this patient population may influence further patient management including intensified risk factor intervention. (orig.)

  11. Non-invasive Optical Molecular Imaging for Cancer Detection

    Science.gov (United States)

    Luo, Zhen

    Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide

  12. Molecular imaging based on metabolic glycoengineering and bioorthogonal click chemistry.

    Science.gov (United States)

    Yoon, Hong Yeol; Koo, Heebeom; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-07-01

    Metabolic glycoengineering is a powerful technique that can introduce various chemical groups to cellular glycan by treatment of unnatural monosaccharide. Particularly, this technique has enabled many challenging trials for molecular imaging in combination with click chemistry, which provides fast and specific chemical conjugation reaction of imaging probes to metabolically-modified live cells. This review introduces recent progress in molecular imaging based on the combination of these two cutting-edge techniques. First, these techniques showed promising results in specific tumor cell imaging for cancer diagnosis and therapy. The related researches showed the surface of tumor cells could be labeled with bioorthogonal chemical groups by metabolic glycoengineering, which can be further conjugated with fluorescence dyes or nanoparticles with imaging probes by click chemistry, in vitro and in vivo. This method can be applied to heterogeneous tumor cells regardless of genetic properties of different tumor cells. Furthermore, the amount of targeting moieties on tumor cells can be freely controlled externally by treatment of unnatural monosaccharide. Second, this sequential use of metabolic glycoengineering and click chemistry is also useful in cell tracking to monitor the localization of the inoculated therapeutic cells including chondrocytes and stem cells. This therapeutic cell-labeling technique provided excellent viability of chondrocytes and stem cells during the whole process in vitro and in vivo. It can provide long-term and safe therapeutic cell imaging compared to traditional methods. These overall studies demonstrate the great potential of metabolic glycoengineering and click chemistry in live cell imaging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

    Science.gov (United States)

    Wachsmann, Jason; Peng, Fangyu

    2016-01-07

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

  14. Quantification and confocal imaging of protein specific molecularly imprinted polymers.

    Science.gov (United States)

    Hawkins, Daniel M; Trache, Andreea; Ellis, E Ann; Stevenson, Derek; Holzenburg, Andreas; Meininger, Gerald A; Reddy, Subrayal M

    2006-09-01

    We have employed FITC--albumin as the protein template molecule in an aqueous phase molecular imprinted polymer (HydroMIP) strategy. For the first time, the use of a fluorescently labeled template is reported, with subsequent characterization of the smart material to show that the HydroMIP possesses a significant molecular memory in comparison to that of the nonimprinted control polymer (HydroNIP). The imaging of the FITC--albumin imprinted HydroMIP using confocal microscopy is described, with the in situ removal of the imprinted protein displayed in terms of observed changes in the fluorescence of the imprinted polymer, both before and after template elution (using a 10% SDS/10% AcOH (w/v) solution). We also report the imaging of a bovine hemoglobin (BHb) imprinted HydroMIP using two-photon confocal microscopy and describe the effects of template elution upon protein autofluorescence. The findings further contribute to the understanding of aqueous phase molecular imprinting protocols and document the use of fluorescence as a useful tool in template labeling/detection and novel imaging strategies.

  15. Molecular Imaging in Tracking Tumor Stem-Like Cells

    Directory of Open Access Journals (Sweden)

    Tian Xia

    2012-01-01

    Full Text Available Cancer remains a major public health problem in many countries. It was found to contain a subset of cancer stem cells (CSCs that are capable of proliferation and self-renewal, and differentiation into various types of cancer cells. CSCs often display characteristics of chemotherapy resistance and radiotherapy resistance. Numerous putative biomarkers of CSCs are currently identified including CD133, CD44, CD24, ALDH (aldehyde dehydrogenase, and ABCG2. Interestingly, no single marker is exclusively expressed by CSCs. Thus, the various combinations of different biomarkers will be possible to identify CSCs, and considerable work is being done to recognize new ones. In order to demonstrate the mechanisms of resistance and response to therapy and predict the outcome as well as prognosis, the ways to track and identify CSCs will be extremely important. The technologies of molecular imaging will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. Limited studies were investigated on the detection of various types of CSCs by molecular imaging. Although the tracking of circulating CSCs is still hampered by technological challenges, personalized diagnosis and therapies of cancers are expected to be established based on increased understanding of molecular imaging of cancer stem-like cells biomarkers.

  16. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Histone deacetylases and atherosclerosis.

    Science.gov (United States)

    Zheng, Xia-xia; Zhou, Tian; Wang, Xin-An; Tong, Xiao-hong; Ding, Jia-wang

    2015-06-01

    Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic. Accumulating evidence suggests that histone deacetylases(HDACs) play crucial roles in arteriosclerosis. This review summarizes the effect of HDACs and HDAC inhibitors(HDACi) on the progress of atherosclerosis. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Imaging tumor microscopic viscosity in vivo using molecular rotors

    Science.gov (United States)

    Shimolina, Lyubov’ E.; Izquierdo, Maria Angeles; López-Duarte, Ismael; Bull, James A.; Shirmanova, Marina V.; Klapshina, Larisa G.; Zagaynova, Elena V.; Kuimova, Marina K.

    2017-01-01

    The microscopic viscosity plays an essential role in cellular biophysics by controlling the rates of diffusion and bimolecular reactions within the cell interior. While several approaches have emerged that have allowed the measurement of viscosity and diffusion on a single cell level in vitro, the in vivo viscosity monitoring has not yet been realized. Here we report the use of fluorescent molecular rotors in combination with Fluorescence Lifetime Imaging Microscopy (FLIM) to image microscopic viscosity in vivo, both on a single cell level and in connecting tissues of subcutaneous tumors in mice. We find that viscosities recorded from single tumor cells in vivo correlate well with the in vitro values from the same cancer cell line. Importantly, our new method allows both imaging and dynamic monitoring of viscosity changes in real time in live animals and thus it is particularly suitable for diagnostics and monitoring of the progress of treatments that might be accompanied by changes in microscopic viscosity. PMID:28134273

  19. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arif Sheikh

    2017-02-01

    Full Text Available Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1. A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

  20. Molecular imaging by optically-detected electron spin resonance of nitrogen-vacancies in nanodiamond

    OpenAIRE

    Hegyi, Alex; Yablonovitch, Eli

    2012-01-01

    Molecular imaging refers to a class of noninvasive biomedical imaging techniques with the sensitivity and specificity to image biochemical variations in-vivo. An ideal molecular imaging technique visualizes a biochemical target according to a range of criteria, including high spatial and temporal resolution, high contrast relative to non-targeted tissues, depth-independent penetration into tissue, lack of harm to the organism under study, and low cost. Because no existing molecular imaging mo...

  1. The Heinz Nixdorf Recall study and its potential impact on the adoption of atherosclerosis imaging in European primary prevention guidelines.

    Science.gov (United States)

    Mahabadi, Amir A; Möhlenkamp, Stefan; Moebus, Susanne; Dragano, Nico; Kälsch, Hagen; Bauer, Marcus; Jöckel, Karl-Heinz; Erbel, Raimund

    2011-10-01

    Non-contrast-enhanced computed tomography (CT) imaging of the heart enables noninvasive quantification of coronary artery calcification (CAC), a surrogate marker of the atherosclerotic burden in the coronary artery tree. Multiple studies have underlined the ability of CAC score for individual risk stratification and, accordingly, the American Heart Association recommended cardiac CT for risk assessment in individuals with an intermediate risk of cardiovascular events as measured by Framingham Risk Score. However, limitations in transcribing risk stratification algorithms based on American cohort studies into European populations have been acknowledged in the past. Moreover, data on implications for reclassification into higher- or lower-risk groups based on CAC scores were lacking. The Heinz Nixdorf Recall (HNR) study is a population-based cohort study that investigated the ability of CAC scoring in risk prediction for major cardiovascular events above and beyond traditional cardiovascular risk factors. According to Heinz Nixdorf Recall findings, CAC can be used for reclassification, especially in those in the intermediate-risk group, to advise on lifestyle changes for the reclassified low-risk category, or to implement intensive treatments for the reclassified high-risk individuals. This article discusses the present findings of the Heinz Nixdorf Recall Study with respect to the current literature, risk stratification algorithms, and current European guidelines for risk prediction.

  2. Nanodiamond imaging: molecular imaging with optically detected spin resonance of nitrogen-vacancy centers in nanodiamonds

    Science.gov (United States)

    Hegyi, Alex; Yablonovitch, Eli

    2013-03-01

    Nanodiamond imaging is a new molecular imaging modality that takes advantage of nitrogen-vacancy (NV) defects in nanodiamonds to image the distribution of nanodiamonds within a living organism with high sensitivity and high resolution. Nanodiamond is a nontoxic material that is easily conjugated to biomolecules, such that the distribution of nanodiamond within a living organism can be used to elicit physiological information. Unlike the tracers used in other molecular imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), nanodiamonds are stable and thus allow longitudinal imaging of the same organism over a long time span. Unlike fluorescence-based molecular imaging that has a resolution degraded by photon scattering, the resolution of nanodiamond imaging is defined by the strength of a magnetic gradient. To form an image, a magnetic field-free region is created, such as exists halfway between two identical magnets with north poles facing each other. Optical excitation pumps the NVs into a bright fluorescence state, and microwaves transfer them to a dark state, but only for those NVs within the field-free region and resonant with the microwaves. By rastering the field-free region across the sample, the changes in fluorescence yield the nanodiamond concentration. Images of nanodiamond phantoms within chicken breast have been recorded with a prototype system. By modifying the nanodiamond particles and enhancing the imaging system, it should be possible to approach 100 μm resolution and to increase the sensitivity to a 10 nanomolar carbon concentration per root Hz in a mm3 voxel.

  3. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies : new imaging strategies to guide molecular therapies

    NARCIS (Netherlands)

    Malviya, G.; Conti, F.; Chianelli, M.; Scopinaro, F.; Dierckx, R. A.; Signore, A.

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of

  4. How Is Atherosclerosis Treated?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  5. How Is Atherosclerosis Diagnosed?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  6. What Is Atherosclerosis?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  7. What Causes Atherosclerosis?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  8. Living with Atherosclerosis

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  9. Infection and Atherosclerosis Development

    Science.gov (United States)

    Campbell, Lee Ann; Rosenfeld, Michael E.

    2015-01-01

    Atherosclerosis is a chronic disease hallmarked by chronic inflammation, endothelial dysfunction and lipid accumulation in the vasculature. Although lipid modification and deposition are thought to be a major source of the continuous inflammatory stimulus, a large body of evidence suggests that infectious agents may contribute to atherosclerotic processes. This could occur by either direct effects through infection of vascular cells and/or through indirect effects by induction of cytokine and acute phase reactant proteins by infection at other sites. Multiple bacterial and viral pathogens have been associated with atherosclerosis by seroepidemiological studies, identification of the infectious agent in human atherosclerotic tissue, and experimental studies demonstrating an acceleration of atherosclerosis following infection in animal models of atherosclerosis. This review will focus on those infectious agents for which biological plausibility has been demonstrated in animal models and on the challenges of proving a role of infection in human atherosclerotic disease. PMID:26004263

  10. [Epigenetics in atherosclerosis].

    Science.gov (United States)

    Guardiola, Montse; Vallvé, Joan C; Zaina, Silvio; Ribalta, Josep

    2016-01-01

    The association studies based on candidate genes carried on for decades have helped in visualizing the influence of the genetic component in complex diseases such as atherosclerosis, also showing the interaction between different genes and environmental factors. Even with all the knowledge accumulated, there is still some way to go to decipher the individual predisposition to disease, and if we consider the great influence that environmental factors play in the development and progression of atherosclerosis, epigenetics is presented as a key element in trying to expand our knowledge on individual predisposition to atherosclerosis and cardiovascular disease. Epigenetics can be described as the discipline that studies the mechanisms of transcriptional regulation, independent of changes in the sequence of DNA, and mostly induced by environmental factors. This review aims to describe what epigenetics is and how epigenetic mechanisms are involved in atherosclerosis. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  11. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...

  12. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  13. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

    PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  14. Molecular imaging in neurological diseases; Molekulare Bildgebung bei neurologischen Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Reimold, M.; Fougere, C. la [Universitaetsklinikum Tuebingen, Abteilung Nuklearmedizin und Klinische Molekulare Bildgebung, Department Radiologie, Tuebingen (Germany)

    2016-07-15

    In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, {sup 18}F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma. (orig.) [German] Die Magnetresonanztomographie (MRT) weist als Standardverfahren bei neurodegenerativen und neuroonkologischen Fragestellungen eine eingeschraenkte Sensitivitaet und Spezifitaet auf. Die nuklearmedizinische molekulare Bildgebung mit spezifischen Positronenemissionstomographie(PET)- und single-photon-emission-computed-tomography(SPECT)-Tracern ermoeglicht die Darstellung verschiedener molekularer Targets bzw. Stoffwechselprozesse und stellt damit eine wichtige Ergaenzung zur MRT dar. Hier sei exemplarisch auf die Darstellung des Aminosaeuretransports im Rahmen neuroonkologischer Fragestellungen verwiesen, sowie auf die bereits im praeklinischen Stadium der Alzheimer-Demenz nachweisbaren Amyloidablagerungen mit hierfuer seit Kurzem zugelassenen PET-Tracern. Dieser Uebersichtsbeitrag bespricht die klinische Bedeutung bzw. die Indikationen der folgenden nuklearmedizinischen Untersuchungsverfahren: der Amyloid-PET, der {sup 18}F

  15. In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W. [Univ. of Notre Dame, IN (United States); Shrout, J. D. [Univ. of Notre Dame, IN (United States); Sweedler, J. V. [Univ. of Illinois, Urbana-Champaign, IL (United States); Farrand, S. [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2016-01-25

    This document constitutes the final technical report for DE-SC0006642, In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities, a project carried out collaboratively by investigators at Notre Dame and UIUC. The work carried out under DOE support in this project produced advances in two areas: development of new highly sophisticated correlated imaging approaches and the application of these new tools to the growth and differentiation of microbial communities under a variety of environmental conditions. A significant effort involved the creation of technical enhancements and sampling approaches to allow us to advance heterocorrelated mass spectrometry imaging (MSI) and correlated Raman microscopy (CRM) from bacterial cultures and biofilms. We then exploited these measurement advances in heterocorrelated MS/CRM imaging to determine relationship of signaling molecules and excreted signaling molecules produced by P. aeruginosa to conditions relevant to the rhizosphere. In particular, we: (1) developed a laboratory testbed mimic for the rhizosphere to enable microbial growth on slides under controlled conditions; (2) integrated specific measurements of (a) rhamnolipids, (b) quinolone/quinolones, and (c) phenazines specific to P. aeruginosa; and (3) utilized the imaging tools to probe how messenger secretion, quorum sensing and swarming behavior are correlated with behavior.

  16. Technetium-99m Labeled Duramycin: A Novel Molecular Imaging Agent to Detect Apoptosis in Cardiovascular Pathologies

    Science.gov (United States)

    Chaudhry, Farhan

    Apoptosis underlines atherosclerosis and myocardial infarction/reperfusion (IR) injury. An imaging agent targeting apoptosis would increase the specificity of non-invasive imaging of apoptosis in these pathologies. Duramycin binds to phosphatidylethanolamine (PE) on the surface of apoptotic cells and can thus target apoptosis. In this study, technetium-99m labeled duramycin (TcD) was used to image both atherosclerosis and IR injury in rabbits using SPECT/CT. Rabbits were inflicted with atherosclerotic damage, IR injury, or were unmanipulated (control). Also, to assess for detection of therapeutic changes, a cardioprotective agent (minocycline) was used in IR rabbits. TcD, 99mTc-Annexin A5 (positive control), and linear TcD (Duramycin without the binding head to PE) were all imaged using SPECT/CT. Aortic or heart samples were collected with their respective organ samples for gamma counting and histopathology. After correlating the imaging, sample gamma counts, and the histopathology, TcD is a feasible imaging agent for apoptosis in atherosclerotic and IR injury.

  17. Pipe Phantoms With Applications in Molecular Imaging and System Characterization.

    Science.gov (United States)

    Wang, Shiying; Herbst, Elizabeth B; Pye, Stephen D; Moran, Carmel M; Hossack, John A

    2017-01-01

    Pipe (vessel) phantoms mimicking human tissue and blood flow are widely used for cardiovascular related research in medical ultrasound. Pipe phantom studies require the development of materials and liquids that match the acoustic properties of soft tissue, blood vessel wall, and blood. Over recent years, pipe phantoms have been developed to mimic the molecular properties of the simulated blood vessels. In this paper, the design, construction, and functionalization of pipe phantoms are introduced and validated for applications in molecular imaging and ultrasound imaging system characterization. There are three major types of pipe phantoms introduced: 1) a gelatin-based pipe phantom; 2) a polydimethylsiloxane-based pipe phantom; and 3) the "Edinburgh pipe phantom." These phantoms may be used in the validation and assessment of the dynamics of microbubble-based contrast agents and, in the case of a small diameter tube phantom, for assessing imaging system spatial resolution/contrast performance. The materials and procedures required to address each of the phantoms are described.

  18. New aspects of molecular imaging in prostate cancer.

    Science.gov (United States)

    Ceci, Francesco; Castellucci, Paolo; Cerci, Juliano J; Fanti, Stefano

    2017-11-01

    Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on

  19. Lanthanide Complexes in Molecular Magnetic Resonance Imaging and Theranostics.

    Science.gov (United States)

    Lacerda, Sara; Tóth, Éva

    2017-06-21

    Lanthanide complexes have attracted much attention in the biomedical field, and today various imaging applications make use of their versatile magnetic and luminescence properties. In this minireview, we give insight into the mechanistic aspects that allow modulation of the relaxation or chemical exchange saturation transfer (CEST) features, and thus the magnetic resonance imaging (MRI) efficiency of paramagnetic lanthanide chelates in order to create agents that are capable of providing an MRI response as a function of a specific biomarker. We focus on the detection of neurotransmitters, enzymatic activities, and amyloid peptides. We also describe two selected theranostic strategies: 1) a novel approach directed at monitoring drug release from liponanoparticles and 2) molecular or nanoparticle probes for the MRI visualization of photosensitizer delivery in photodynamic therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  1. Dynamical image-charge effect in molecular tunnel junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun; Thygesen, Kristian Sommer

    2014-01-01

    When an electron tunnels between two metal contacts it temporarily induces an image charge (IC) in the electrodes which acts back on the tunneling electron. It is usually assumed that the IC forms instantaneously such that a static model for the image potential applies. Here we investigate how...... the finite IC formation time affects charge transport through a molecule suspended between two electrodes. For a single-level model, an analytical treatment shows that the conductance is suppressed by a factor Z(2), where Z is the quasiparticle renormalization factor, compared to the static IC approximation...... that the dynamical corrections can reduce the conductance by more than a factor of two when compared to static GW or density functional theory where the molecular energy levels have been shifted to match the exact quasiparticle levels....

  2. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-08-01

    Full Text Available Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT, magnetic resonance imaging (MRI, positron emission tomography (PET, as well as nanoprobes for photoacoustic tomography (PAT, two-photon photoluminescence (TPL and surface-enhanced Raman spectroscopy (SERS. Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  3. Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.

    Science.gov (United States)

    Rempel, Brian P; Price, Eric W; Phenix, Christopher P

    2017-01-01

    Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.

  4. Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors

    Science.gov (United States)

    Hosny, Neveen A.; Mohamedi, Graciela; Rademeyer, Paul; Owen, Joshua; Wu, Yilei; Tang, Meng-Xing; Eckersley, Robert J.; Stride, Eleanor; Kuimova, Marina K.

    2013-01-01

    Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a “molecular rotor” embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component. PMID:23690599

  5. Dual Modality Ultrasound-SPET Detector for Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pani, R., E-mail: roberto.pani@uniroma1.it [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Molecular Medicine, ' Sapienza' University, Rome (Italy); Pellegrini, R.; Cinti, M.N. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Molecular Medicine, ' Sapienza' University, Rome (Italy); Bennati, P.; Fabbri, A. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); EDEMOM PhD School of Microelectronics, ' Roma Tre' University, Rome (Italy); Ridolfi, S.; Scafe, R. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Molecular Medicine, ' Sapienza' University, Rome (Italy); De Vincentis, G. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Radiological Science, ' Sapienza' University, Rome (Italy); Di Castro, E.; Polli, N.S.A.; Caratozzolo, M. [Dept. of Radiological Science, ' Sapienza' University, Rome (Italy); Mattioli, M.; Boccaccio, P. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Moschini, G. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Physics, University of Padua, Padua (Italy); Lanconelli, N.; Lo Meo, S.; Navarria, F. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Physics, ' Alma Mater Studiorum' University, Bologne (Italy); Sacco, D. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); I.S.P.E.S.L. Monteporzio, Rome (Italy); Cencelli, V.O. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy); Dept. of Physics, ' Roma Tre' University, Rome (Italy); Baroncelli, T. [I.N.F.N. Istituto Nazionale di Fisica Nucleare (Italy)

    2011-06-15

    We present an innovative compact dual-modality detector, which integrates an ultrasound probe with a scintigrafic {gamma}-camera for molecular imaging in medicine, in order to get both morphological and functional information in a single three-dimensional image. The scintigraphic detector consists of a 2x2 array of a multi-anode PMT Hamamatsu H8500-Mod8 and a 4.0 mm thick continuous LaBr{sub 3}(Ce) crystal equipped with four segment slant-hole collimators for single photon imaging (SPET). The collimator permits to recover the depth of a lesion by rotating around its vertical axis (z) without the need of rotating the camera around the investigated object. This detector can take advantage from being positioned close to the object and overcome the intrinsic limitations in spatial resolution arising from the geometry of SPET/CT gantry. The aim of this work is to describe preliminary phantom analysis and to provide a 3D US/SPET image.

  6. Ultrasound in Radiology: from Anatomic, Functional, Molecular Imaging to Drug Delivery and Image-Guided Therapy

    Science.gov (United States)

    Klibanov, Alexander L.; Hossack, John A.

    2015-01-01

    During the past decade, ultrasound has expanded medical imaging well beyond the “traditional” radiology setting - a combination of portability, low cost and ease of use makes ultrasound imaging an indispensable tool for radiologists as well as for other medical professionals who need to obtain imaging diagnosis or guide a therapeutic intervention quickly and efficiently. Ultrasound combines excellent ability for deep penetration into soft tissues with very good spatial resolution, with only a few exceptions (i.e. those involving overlying bone or gas). Real-time imaging (up to hundreds and thousands frames per second) enables guidance of therapeutic procedures and biopsies; characterization of the mechanical properties of the tissues greatly aids with the accuracy of the procedures. The ability of ultrasound to deposit energy locally brings about the potential for localized intervention encompassing: tissue ablation, enhancing penetration through the natural barriers to drug delivery in the body and triggering drug release from carrier micro- and nanoparticles. The use of microbubble contrast agents brings the ability to monitor and quantify tissue perfusion, and microbubble targeting with ligand-decorated microbubbles brings the ability to obtain molecular biomarker information, i.e., ultrasound molecular imaging. Overall, ultrasound has become the most widely used imaging modality in modern medicine; it will continue to grow and expand. PMID:26200224

  7. Systemic atherosclerosis and voiding symptom.

    Science.gov (United States)

    Yeniel, A Ozgur; Ergenoglu, A Mete; Meseri, Reci; Ari, Anıl; Sancar, Ceren; Itil, Ismail Mete

    2017-03-01

    To evaluate the effect of atherosclerosis on the storage and voiding symptoms of the bladder in women with overactive bladder (OAB). We retrospectively reviewed the charts of women with OAB who were evaluated between 2013 and 2015 in our urogynecology unit. Charts were assessed for history, examination findings, urinary diary, quality of life (QOL) questionnaires, urodynamic studies (UDSs), and four main risk factors for atherosclerosis: hypertension, diabetes mellitus, smoking, and hyperlipidemia. In a previous study, these were defined as vascular risk factors. Cases were excluded for insufficient data, diabetes mellitus with dysregulated blood glucose, or prolapse greater than 1cm to avoid confusing bladder outlet obstruction. We included 167 eligible cases in this study. We evaluated storage and voiding symptoms such as frequency, nocturia, residual urine volume, and voiding difficulties and UDS findings such as maximum bladder capacity, first desire, strong desire, detrusor overactivity, and bladder contractility index. The vascular risk score was categorized as "no risk" if the woman did not have any of the four risk factors and "at risk" if she had any of the factors. Independent sample t-test and chi-square tests were performed for analyses. Among the participants (n=167), 71.9% had at least one vascular risk factor. Those who were at risk were facing significantly more wet-type OAB (p=0.003) and nocturia (p=0.023). Moreover, mean age (p=0.008) and mean gravidity (p=0.020) were significantly higher in the at-risk group, whereas mean total nocturia QOL questionnaire scores (p=0.029) were significantly lower. Our findings suggest that aging and atherosclerosis may be associated with severe OAB and poorer QOL. Nocturia and related parameters of poor quality can be explained by impaired bladder neck perfusion. Future trials need to assess vascular and molecular changes in women with OAB. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging.

    Science.gov (United States)

    Ughi, Giovanni J; Wang, Hao; Gerbaud, Edouard; Gardecki, Joseph A; Fard, Ali M; Hamidi, Ehsan; Vacas-Jacques, Paulino; Rosenberg, Mireille; Jaffer, Farouc A; Tearney, Guillermo J

    2016-11-01

    The authors present the clinical imaging of human coronary arteries in vivo using a multimodality optical coherence tomography (OCT) and near-infrared autofluorescence (NIRAF) intravascular imaging system and catheter. Although intravascular OCT is capable of providing microstructural images of coronary atherosclerotic lesions, it is limited in its capability to ascertain the compositional/molecular features of plaque. A recent study in cadaver coronary plaque showed that endogenous NIRAF is elevated in necrotic core lesions. The combination of these 2 technologies in 1 device may therefore provide synergistic data to aid in the diagnosis of coronary pathology in vivo. We developed a dual-modality intravascular imaging system and 2.6-F catheter that can simultaneously acquire OCT and NIRAF data from the same location on the artery wall. This technology was used to obtain volumetric OCT-NIRAF images from 12 patients with coronary artery disease undergoing percutaneous coronary intervention. Images were acquired during a brief, nonocclusive 3- to 4-ml/s contrast purge at a speed of 100 frames/s and a pullback rate of 20 or 40 mm/s. OCT-NIRAF data were analyzed to determine the distribution of the NIRAF signal with respect to OCT-delineated plaque morphological features. High-quality intracoronary OCT and NIRAF image data (>50-mm pullback length) were successfully acquired without complication in all patients (17 coronary arteries). The maximum NIRAF signal intensity of each plaque was compared with OCT-defined type, showing a statistically significant difference between plaque types (1-way analysis of variance, p < 0.0001). Interestingly, coronary arterial NIRAF intensity was elevated only focally in plaques with a high-risk morphological phenotype (p < 0.05), including OCT fibroatheroma, plaque rupture, and fibroatheroma associated with in-stent restenosis. This OCT-NIRAF study demonstrates that dual-modality microstructural and fluorescence intracoronary

  9. Vascular ultrasound for atherosclerosis imaging

    NARCIS (Netherlands)

    C.L. de Korte (Chris); H.H.G. Hansen (Hendrik); A.F.W. van der Steen (Ton)

    2011-01-01

    textabstractCardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the

  10. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  11. Molecular Beacons: Powerful Tools for Imaging RNA in Living Cells

    Directory of Open Access Journals (Sweden)

    Ricardo Monroy-Contreras

    2011-01-01

    Full Text Available Recent advances in RNA functional studies highlights the pivotal role of these molecules in cell physiology. Diverse methods have been implemented to measure the expression levels of various RNA species, using either purified RNA or fixed cells. Despite the fact that fixed cells offer the possibility to observe the spatial distribution of RNA, assays with capability to real-time monitoring RNA transport into living cells are needed to further understand the role of RNA dynamics in cellular functions. Molecular beacons (MBs are stem-loop hairpin-structured oligonucleotides equipped with a fluorescence quencher at one end and a fluorescent dye (also called reporter or fluorophore at the opposite end. This structure permits that MB in the absence of their target complementary sequence do not fluoresce. Upon binding to targets, MBs emit fluorescence, due to the spatial separation of the quencher and the reporter. Molecular beacons are promising probes for the development of RNA imaging techniques; nevertheless much work remains to be done in order to obtain a robust technology for imaging various RNA molecules together in real time and in living cells. The present work concentrates on the different requirements needed to use successfully MB for cellular studies, summarizing recent advances in this area.

  12. Tunable Molecular Logic Gates Designed for Imaging Released Neurotransmitters.

    Science.gov (United States)

    Klockow, Jessica L; Hettie, Kenneth S; Secor, Kristen E; Barman, Dipti N; Glass, Timothy E

    2015-08-03

    Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque using (68)Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden.

    Science.gov (United States)

    Weiberg, Desiree; Thackeray, James T; Daum, Guenter; Sohns, Jan M; Kropf, Saskia; Wester, Hans-Jürgen; Ross, Tobias L; Bengel, Frank M; Derlin, Thorsten

    2017-08-03

    The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4+ cell types in cardiovascular diseases including atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of (68)Ga-Pentixafor, a specific CXCR4 ligand for positron emission tomography (PET). Methods: Data of fifty-one patients who underwent (68)Ga-Pentixafor PET/computed tomography (PET/CT) for non-cardiovascular indications were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed qualitatively and semiquantitatively by blood-pool-corrected target-to-background ratios (TBRs). Tracer uptake was compared with calcified plaque burden and cardiovascular risk factors. Results: Focal arterial uptake of (68)Ga-Pentixafor was seen at 1411 sites in 51 (100%) of patients. (68)Ga-Pentixafor uptake was significantly associated with calcified plaque burden (P<0.0001) and cardiovascular risk factors including age (P<0.0001), arterial hypertension (P<0.0001), hypercholesterolemia (P = 0.0005), history of smoking (P = 0.01), and prior cardiovascular events (P = 0.0004). Both the prevalence (P<0.0001) and signal intensity (P = 0.009) of (68)Ga-Pentixafor uptake increased as the number of risk factors increased. Conclusion:(68)Ga-Pentixafor PET/CT is suitable for non-invasive, highly specific PET imaging of CXCR4 expression in the atherosclerotic arterial wall. Arterial wall (68)Ga-Pentixafor uptake is significantly associated with surrogate markers of atherosclerosis, and is linked to the presence of cardiovascular risk factors. (68)Ga-Pentixafor signal is higher in patients with a high-risk profile, and may hold promise for identification of vulnerable plaque. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Molecular imaging by optically-detected electron spin resonance of nitrogen-vacancies in nanodiamond

    CERN Document Server

    Hegyi, Alex

    2012-01-01

    Molecular imaging refers to a class of noninvasive biomedical imaging techniques with the sensitivity and specificity to image biochemical variations in-vivo. An ideal molecular imaging technique visualizes a biochemical target according to a range of criteria, including high spatial and temporal resolution, high contrast relative to non-targeted tissues, depth-independent penetration into tissue, lack of harm to the organism under study, and low cost. Because no existing molecular imaging modality is ideal for all purposes, new imaging approaches are needed. Here we demonstrate a novel molecular imaging approach, called nanodiamond imaging, that uses nanodiamonds containing nitrogen-vacancy (NV) color centers as an imaging agent, and image nanodiamond targets in pieces of chicken breast. Nanodiamonds can be tagged with biologically active molecules so they bind to specific receptors; their distribution can then be quantified in-vivo via optically-detected magnetic resonance of the NVs. In effect, we are demo...

  15. Graphene-based nanomaterials as molecular imaging agents.

    Science.gov (United States)

    Garg, Bhaskar; Sung, Chu-Hsun; Ling, Yong-Chien

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed. © 2015 Wiley Periodicals, Inc.

  16. Integrin signaling in atherosclerosis.

    Science.gov (United States)

    Finney, Alexandra C; Stokes, Karen Y; Pattillo, Christopher B; Orr, A Wayne

    2017-06-01

    Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques. Integrin signaling has been shown to regulate endothelial phenotype, facilitate leukocyte homing, affect leukocyte function, and drive smooth muscle fibroproliferative remodeling. In addition, integrin signaling in platelets contributes to the thrombotic complications that typically drive the clinical manifestation of cardiovascular disease. In this review, we examine the current literature on integrin regulation of atherosclerotic plaque development and the suitability of integrins as potential therapeutic targets to limit cardiovascular disease and its complications.

  17. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    Cardiovascular disease (CVD) is the major cause of premature deaths worldwide. Coronary heart disease is the most common CVD, caused by atherosclerosis in the coronary arteries. Atherosclerosis is a multifactorial disease influenced by both genetic and environmental factors. WHO has in 2007 listed...... in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...... for decades for their natural ability to reduce cholesterol levels in the blood. In the last decade numerous food products added phytosterol esters have been placed on the market, e.g. yellow fat spread, yoghurt, dressing. The products are being marketed as a natural means for people who want to lower...

  18. Alternative screening for women with dense breasts: breast-specific gamma imaging (molecular breast imaging).

    Science.gov (United States)

    Holbrook, Anna; Newel, Mary S

    2015-02-01

    OBJECTIVE. Given mammography's limitations in evaluating dense breasts, examination with breast-specific gamma imaging (BSGI)-also called molecular breast imaging (MBI)-has been proposed. We review the literature pertinent to the performance of BSGI in patients with dense breasts. CONCLUSION. Many studies have reported the sensitivity of BSGI in finding cancers even in dense breasts. However, BSGI has not yet been validated as an effective screening tool in large prospective studies. In addition, whole-body dose remains a significant concern.

  19. Molecular Imaging Of Metabolic Reprogramming In Mutant IDH Cells

    Directory of Open Access Journals (Sweden)

    Pavithra eViswanath

    2016-03-01

    Full Text Available Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG. Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG. In turn, 2-HG, which has been termed an oncometabolite, inhibits key α-KG- dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprogramming that extends beyond 2-HG production, and this reprogramming often differs from what has been previously reported in other cancer types. In this review we will discuss in detail what is known to date about the metabolic reprogramming of mutant IDH cells and how this reprogramming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

  20. Molecular Imaging of Metabolic Reprograming in Mutant IDH Cells.

    Science.gov (United States)

    Viswanath, Pavithra; Chaumeil, Myriam M; Ronen, Sabrina M

    2016-01-01

    Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG). Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG). In turn, 2-HG, which has been termed an "oncometabolite," inhibits key α-KG-dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprograming that extends beyond 2-HG production, and this reprograming often differs from what has been previously reported in other cancer types. In this review, we will discuss in detail what is known to date about the metabolic reprograming of mutant IDH cells, and how this reprograming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells, and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

  1. Epicardial fat is associated with severity of subclinical coronary atherosclerosis in familial hypercholesterolemia.

    Science.gov (United States)

    Mangili, Leonardo C; Mangili, Otavio C; Bittencourt, Márcio S; Miname, Márcio H; Harada, Paulo H; Lima, Leonardo M; Rochitte, Carlos E; Santos, Raul D

    2016-11-01

    Familial hypercholesterolemia (FH) is a common genetic disorder characterized by elevated blood cholesterol, increased prevalence of subclinical atherosclerosis and high risk of premature coronary heart disease. However, this risk is not explained solely by elevated LDL-cholesterol concentrations, and other factors may influence atherosclerosis development. There is evidence that increased adiposity may predispose to atherosclerosis in FH. Epicardial fat has been associated with subclinical coronary atherosclerosis in the general population. This study evaluated the association of epicardial fat (EFV) volume with the presence and extent of subclinical coronary atherosclerosis detected by computed tomography angiography in FH patients. Ninety-seven FH subjects (35% male, mean age 45 ± 13 years, LDL-C 281 ± 56 mg/dL, 67% with proven molecular defects) underwent computed tomography angiography and coronary artery calcium (CAC) scoring. EFV was measured in non-contrast images using a semi-automated method. Segment-stenosis score (SSS) and segment-involvement score (SIS) were calculated. Multivariate Poisson regression was utilized to assess an independent association of EFV with coronary atherosclerotic burden. EFV was positively associated with age, body mass index, waist circumference, blood glucose, the presence of the metabolic syndrome components, but not with LDL-C. After adjusting for confounders and abdominal circumference, an independent association (shown as β coefficients and 95% confidence intervals) of EVF with CAC scores [β = 0.263 (0.234; 0.292), p=0.000], SIS [β = 0.304 (0.141; 0.465) p=0.000] and SSS [β = 0.296 (0.121; 0.471), p=0.001] was found. In FH, EFV was independently associated with coronary atherosclerotic presence and severity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Non-invasive molecular imaging of prostate cancer lymph node metastasis

    Science.gov (United States)

    Pouliot, Frédéric; Johnson, Mai; Wu, Lily

    2009-01-01

    Imaging in medicine has been classically based on the anatomical description of organs. In the past 15 years, new imaging techniques based on gene expression that characterize a pathological process have been developed. Molecular imaging is the use of such molecules to image cell-specific characteristics. Here, we review recent advances in molecular imaging, taking as our prime example lymph node (LN) metastasis in prostate cancer. We describe the new techniques and compare their accuracy in detecting LN metastasis in prostate cancer. We also present new molecular strategies for improving tumor detection using adenoviruses, molecular promoters and amplification systems. Finally, we present the concept of ‘in vivo pathology’, which envisages using molecular imaging to accurately localize metastatic lesions based on the molecular signature of the disease. PMID:19482514

  3. Structured illumination microscopy for vibrational molecular imaging (Conference Presentation)

    Science.gov (United States)

    Watanabe, Kozue; Palonpon, Almar F.; Smith, Nicholas I.; Chiu, Liang-da; Kasai, Atsushi; Hashimoto, Hitoshi; Kawata, Satoshi; Fujita, Katsumasa

    2016-09-01

    Raman microscopy is a powerful tool for analytical imaging. The wavelength shift of Raman scattering corresponds to molecular vibrational energy. Therefore, we can access rich chemical information, such as distribution, concentration, and chemical environment of sample molecules. Despite these strengths of Raman microscopy, the spatial resolution has been a limiting factor for many practical applications. In this study, we developed a large-area, high-resolution Raman microscope by utilizing structured illumination microscopy (SIM) to overcome the spatial resolution limit. A structured line-illumination (SLI) Raman microscope was constructed. The structured illumination is introduced along the line direction by the interference of two line-shaped beams. In SIM, the spatial frequency mixing between structured illumination and Raman scattering from the sample allows access to the high spatial frequency information beyond the conventional cut-off. As a result, the FWHM of 40-nm fluorescence particle images showed a clear resolution enhancement in the line direction: 366 nm in LI and 199 nm in SLI microscope. Using the developed microscope, we successfully demonstrated high-resolution Raman imaging of various kinds of specimens, such as few-layer graphene, graphite, mouse brain tissue, and polymer nanoparticles. The high resolution Raman images showed the capability to extract original spectral features from the mixed Raman spectra of a multi-component sample because of the enhanced spatial resolution, which is advantageous in observing complex spectral features. The Raman microscopy technique reported here enables us to see the detailed chemical structures of chemical, biological, and medical samples with a spatial resolution smaller than 200 nm.

  4. HDL signaling and protection against coronary artery atherosclerosis in mice

    OpenAIRE

    Bernardo L Trigatti; Fuller, Mark

    2015-01-01

    Abstract Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke, important causes of morbidity and mortality across the globe. Abundant epidemiological studies demonstrate that high levels of high density lipoprotein (HDL) are associated with reduced risk of atherosclerosis and preclinical, animal model studies demonstrate that this association is causative. Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic a...

  5. Molecular Imaging and Precision Medicine in Lung Cancer.

    Science.gov (United States)

    Zukotynski, Katherine A; Gerbaudo, Victor H

    2017-01-01

    Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  6. Molecular imaging of proteins in tissues by mass spectrometry.

    Science.gov (United States)

    Seeley, Erin H; Caprioli, Richard M

    2008-11-25

    Imaging MS (IMS) is an emerging technology that permits the direct analysis and determination of the distribution of molecules in tissue sections. Biological molecules such as proteins, peptides, lipids, xenobiotics, and metabolites can be analyzed in a high-throughput manner with molecular specificity not readily achievable through other means. Tissues are analyzed intact and thus spatial localization of molecules within a tissue is preserved. Several studies are presented that focus on the unique types of information obtainable by IMS, such as Abeta isoform distributions in Alzheimer's plaques, protein maps in mouse brain, and spatial protein distributions in human breast carcinoma. The analysis of a biopsy taken 100 years ago from a patient with amyloidosis illustrates the use of IMS with formalin-fixed tissues. Finally, the registration and correlation of IMS with MRI is presented.

  7. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    Science.gov (United States)

    Vermeulen, Jeroen F; van Brussel, Aram S A; van der Groep, Petra; Morsink, Folkert H M; Bult, Peter; van der Wall, Elsken; van Diest, Paul J

    2012-06-13

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  8. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  9. Phosphatidylserine in atherosclerosis

    OpenAIRE

    Darabi, Maryam; Kontush, Anatol

    2016-01-01

    International audience; Purpose of review: It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating cholesterol metabolism, influencing inflammatory response and regulating coagulation system, and discuss promising phosphatidylserine-based therapeutic approaches and detection techniques in atherosclerosis.

  10. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  11. [Atherosclerosis and infection?].

    Science.gov (United States)

    Zeman, K

    2006-09-01

    Atherosclerosis is guided by chronicle inflammation process. In the last decades of the 20th century, studies considering infection another possible risk factor of atherosclerosis development were written. Helicobacter pylori, Porphyromas gingivalis, some viruses but most frequently Chlamydia pneumonie are infection agens mentioned in these studies. Some of them emphasize also combined infections caused by more pathogenic factors having influence on vascular inflammation. Serological, epidemiological, histological and imunological studies show the pathogenic influence of acute or chronic infections. Many studies selected makrolid antibiotics as treatment in patients with ischaemic heart disease. However, existing experience with antibiotics did not bring clear results. These studies have mentioned the fact antibiotics have not been indicated as treatment in patients with acute or chronic vascular system infliction by atherosclerosis. Since the experimental and clinical research of influence of inflammations on the development of atherosclerosis moved forward a lot, no exact evidence of this complicated pathogenic mechanism was given. It will obviously take some time to confirm whether the relation between infections and artherosclerosis is causal, i.e. initiating the pathogenic process, accelerating it or keeping it alive.

  12. Animal Models of Atherosclerosis

    Science.gov (United States)

    Getz, Godfrey S.; Reardon, Catherine A.

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

  13. Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles

    Science.gov (United States)

    Seekell, Kevin; Crow, Matthew J.; Marinakos, Stella; Ostrander, Julie; Chilkoti, Ashutosh; Wax, Adam

    2011-11-01

    This work presents simultaneous imaging and detection of three different cell receptors using three types of plasmonic nanoparticles (NPs). The size, shape, and composition-dependent scattering profiles of these NPs allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, tags consisting of anti-epidermal growth factor receptor gold nanorods, anti-insulin-like growth factor 1-R silver nanospheres, and human epidermal growth factor receptor 2Ab gold nanospheres were developed to monitor the expression of receptors commonly overexpressed by cancer cells. These labels were chosen because they scatter strongly in distinct spectral windows. A hyperspectral darkfield microspectroscopy system was developed to record the scattering spectra of cells labeled with these molecular tags. Simultaneous monitoring of multiple tags may lead to applications such as profiling of cell line immunophenotype and investigation of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze NP tag specificity as well as their interactions. Distinct resonance peaks were observed in these studies, showing the ability to characterize cell lines using conjugated NPs. However, interpreting shifts in these peaks due to changes in a cellular dielectric environment may be complicated by plasmon coupling between NPs bound to proximal receptors and other coupling mechanisms due to the receptors themselves.

  14. Air Pollution and the microvasculature: a cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA.

    Directory of Open Access Journals (Sweden)

    Sara D Adar

    2010-11-01

    Full Text Available Long- and short-term exposures to air pollution, especially fine particulate matter (PM(2.5, have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE and central retinal venular equivalents (CRVE, were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA participants between 2002 and 2003. Study participants (46 to 87 years of age were without clinical cardiovascular disease at the baseline examination (2000-2002. Long-term outdoor concentrations of PM(2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM(2.5. These relationships were observed in a joint exposure model with -0.8 µm (95% confidence interval [CI] -1.1 to -0.5 and -0.4 µm (95% CI -0

  15. Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2015-09-01

    Full Text Available Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging (CLI, and optical image-guided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

  16. Multi-pinhole fluorescent x-ray computed tomography for molecular imaging

    National Research Council Canada - National Science Library

    Tenta Sasaya; Naoki Sunaguchi; Kazuyuki Hyodo; Tsutomu Zeniya; Tetsuya Yuasa

    2017-01-01

    We propose a multi-pinhole fluorescent x-ray computed tomography (mp-FXCT) technique for preclinical molecular imaging that can provide the complete data necessary to produce 3-D tomographic images during anaesthesia...

  17. Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

    2010-08-15

    Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

  18. Molecular Imaging Markers to Track Huntington's Disease Pathology.

    Science.gov (United States)

    Wilson, Heather; De Micco, Rosa; Niccolini, Flavia; Politis, Marios

    2017-01-01

    Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology. While advances have been made, the precise pathophysiological mechanisms underlying HD are unclear. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have been employed to understand HD pathology in presymptomatic and symptomatic disease stages. PET imaging uses radioactive tracers to detect specific changes, at a molecular level, which could be used as markers of HD progression and to monitor response to therapeutic treatments for HD gene expansion carriers (HDGECs). This review focuses on available PET techniques, employed in cross-sectional and longitudinal human studies, as biomarkers for HD, and highlights future potential PET targets. PET studies have assessed changes in postsynaptic dopaminergic receptors, brain metabolism, microglial activation, and recently phosphodiesterase 10A (PDE10A) as markers to track HD progression. Alterations in PDE10A expression are the earliest biochemical change identified in HD gene carriers up to 43 years before predicted symptomatic onset. Thus, PDE10A expression could be a promising marker to track HD progression from early premanifest disease stages. Other PET targets which have been less well investigated as biomarkers include cannabinoid, adenosine, and GABA receptors. Future longitudinal studies are required to fully validate these PET biomarkers for use to track disease progression from far-onset premanifest to manifest HD stages. PET imaging

  19. Optical molecular imaging of hypoxic breast cancer - From prospect to preclinical practice

    OpenAIRE

    van Brussel, A.S.A.

    2013-01-01

    Current imaging modalities for breast cancer diagnosis and therapy monitoring either lack sensitivity, specificity, make use of radiation and/or give images of limited resolution. Optical molecular imaging is a novel technique that detects light emitted by (breast)cancer-specific probes with a sensitive camera. As hypoxia is a common condition in solid tumors, proteins upregulated in hypoxic cells are of special interest as target for molecular imaging of breast cancer. In this thesis we revi...

  20. HDL signaling and protection against coronary artery atherosclerosis in mice.

    Science.gov (United States)

    Trigatti, Bernardo L; Fuller, Mark

    2016-03-01

    Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke, important causes of morbidity and mortality across the globe. Abundant epidemiological studies demonstrate that high levels of high density lipoprotein (HDL) are associated with reduced risk of atherosclerosis and preclinical, animal model studies demonstrate that this association is causative. Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics. Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall. These signaling responses require the HDL receptor, scavenger receptor class B type 1 (SR-B1), an adaptor protein (PDZK1) that binds to the cytosolic C terminus of SR-B1, Akt1 activation and (at least in endothelial cells) activation of endothelial NO synthase (eNOS). Mouse models of atherosclerosis, exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice (apoE or LDLR KO) develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis. On the other hand, inactivation of each of the components of HDL signaling (above) in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease. © 2016 by the Journal of Biomedical Research. All rights reserved.

  1. Coronary, Carotid, and Lower-extremity Atherosclerosis and Their Interrelationship in Danish Patients with Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Kay, Susan Due; Poulsen, Mikael Kjaer; Diederichsen, Axel Cosmus Pyndt

    2015-01-01

    OBJECTIVE: Atherosclerosis is highly prevalent among patients with systemic lupus erythematosus (SLE), but has been demonstrated predominantly in non-European SLE cohorts and few investigations have included more than 1 imaging modality. We aimed to investigate the prevalence of atherosclerosis...... regression model, age (p Systemic Lupus International Collaborating Clinics (SLICC; p = 0.008) were significant independent risk factors for atherosclerosis at any vascular territory. CONCLUSION: Atherosclerosis is highly prevalent among Danish patients with SLE...

  2. Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging

    Science.gov (United States)

    Tichauer, Kenneth M.; Deharvengt, Sophie J.; Samkoe, Kimberley S.; Gunn, Jason R.; Bosenberg, Marcus W.; Turk, Mary-Jo; Hasan, Tayyaba; Stan, Radu V.; Pogue, Brian W.

    2014-01-01

    Purpose Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations. Procedures Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system. Results The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors. Conclusions This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo. PMID:24217944

  3. Contributions on biomedical imaging, with a side-look at molecular imaging; Beitraege zur biomedizinischen Bildgebung mit einem Seitenblick auf Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, G. (ed.)

    2004-05-01

    This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [German] In diesem Bericht sind einige Beitraege zum Gebiet 'Bildgebende Verfahren in Biologie und Medizin' zusammengestellt. Sie stammen saemtlich aus dem Institut fuer Biomathematik und Biometrie, IBB, am Forschungszentrum fuer Umwelt und Gesundheit, GSF, in Muenchen/Neuherberg, und seinem engeren Umfeld. Ziel war es, zu sichten, was in und um diesen Themenkreis herum an Wissen und sonstiger Kompetenz hier vorhanden ist. Einige am IBB etablierte Gebiete wie Roentgen-Mammographie oder funktionelle Magnetresonanztherapie wurden ausgeblendet. Der Grund ist die Fokussierung auf ein nicht exakt definierbares, neues Gebiet der Bildgebung, das unter dem Namen 'Molecular Imaging' kursiert und derzeit Furore macht macht. (orig.)

  4. Molecular Tension Probes for Imaging Forces at the Cell Surface.

    Science.gov (United States)

    Liu, Yang; Galior, Kornelia; Ma, Victor Pui-Yan; Salaita, Khalid

    2017-11-21

    Mechanical forces are essential for a variety of biological processes ranging from transcription and translation to cell adhesion, migration, and differentiation. Through the activation of mechanosensitive signaling pathways, cells sense and respond to physical stimuli from the surrounding environment, a process widely known as mechanotransduction. At the cell membrane, many signaling receptors, such as integrins, cadherins and T- or B-cell receptors, bind to their ligands on the surface of adjacent cells or the extracellular matrix (ECM) to mediate mechanotransduction. Upon ligation, these receptor-ligand bonds transmit piconewton (pN) mechanical forces that are generated, in part, by the cytoskeleton. Importantly, these forces expose cryptic sites within mechanosensitive proteins and modulate the binding kinetics (on/off rate) of receptor-ligand complexes to further fine-tune mechanotransduction and the corresponding cell behavior. Over the past three decades, two categories of methods have been developed to measure cell receptor forces. The first class is traction force microscopy (TFM) and micropost array detectors (mPADs). In these methods, cells are cultured on elastic polymers or microstructures that deform under mechanical forces. The second category of techniques is single molecule force spectroscopy (SMFS) including atomic force microscopy (AFM), optical or magnetic tweezers, and biomembrane force probe (BFP). In SMFS, the experimenter applies external forces to probe the mechanics of individual cells or single receptor-ligand complexes, serially, one bond at a time. Although these techniques are powerful, the limited throughput of SMFS and the nN force sensitivity of TFM have hindered further elucidation of the molecular mechanisms of mechanotransduction. In this Account, we introduce the recent advent of molecular tension fluorescence microscopy (MTFM) as an emerging tool for molecular imaging of receptor mechanics in living cells. MTFM probes are

  5. The molecular imaging approach to image infections and inflammation by nuclear medicine techniques.

    Science.gov (United States)

    Signore, Alberto; Glaudemans, Andor W J M

    2011-12-01

    Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines.

  6. Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging

    NARCIS (Netherlands)

    Meng, C.; Janssen, M.H.M.

    2015-01-01

    Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the

  7. Insulin resistance and atherosclerosis

    OpenAIRE

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent fi...

  8. Introduction to the special issue on molecular imaging in radiation biology.

    Science.gov (United States)

    Humm, John L; Dewhirst, Mark W; Bhujwalla, Zaver M

    2012-04-01

    Molecular imaging is an evolving science that is concerned with the development of novel imaging probes and biomarkers that can be used to non-invasively image molecular and cellular processes. This special issue approaches molecular imaging in the context of radiation research, focusing on biomarkers and imaging methods that provide measurable signals that can assist in the quantification of radiation-induced effects of living systems at the physical, chemical and biological levels. The potential to image molecular changes in response to a radiation insult opens new and exciting opportunities for a more profound understanding of radiation biology, with the possibility of translation of these techniques to radiotherapy practice. This special issue brings together 14 reviews dedicated to the use of molecular imaging in the field of radiation research. The initial three reviews are introductory overviews of the key molecular imaging modalities: magnetic resonance, nuclear and optical. This is followed by 11 reviews each focusing on a specialist area within the field of radiation research. These include: hypoxia and perfusion, tissue metabolism, normal tissue injury, cell death and viability, receptor targeting and nanotechnology, reporter genes, reactive oxygen species (ROS), and biological dosimetry. Over the preceding decade, molecular imaging brought significant new advances to our understanding of every area of radiation biology. This special issue shows us these advances and points to the vibrant future of our field armed with these new capabilities.

  9. Role of Micronutrients on Subclinical Atherosclerosis Micronutrients in Subclinical Atherosclerosis.

    Science.gov (United States)

    Kocyigit, Duygu; Gurses, Kadri Murat; Yalcin, Muhammed Ulvi; Tokgozoglu, Lale

    2016-01-01

    Atherosclerotic cardiovascular disease (CVD) leading to coronary heart disease is the leading cause of morbidity and mortality in the world. Nutrition is one of the key factors in the etiology of atherosclerosis. Micronutrient supplements are widely used to prevent many chronic diseases including atherosclerosis. However, scientific evidence regarding this issue is still insufficient and current data on the association of dietary micronutrients and CVD risk is contradictory. Most of the randomized studies have failed to demonstrate beneficial effects of micronutrient supplementation on markers of subclinical atherosclerosis. In this review, role of each micronutrient on subclinical atherosclerosis will be evaluated thoroughly.

  10. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

    Science.gov (United States)

    Xue, Yong; Chen, Shihui; Liu, Yong

    2017-01-01

    Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

  11. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

    Directory of Open Access Journals (Sweden)

    Yong Xue

    2017-01-01

    Full Text Available Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging.

  12. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey.

    Science.gov (United States)

    Xue, Yong; Chen, Shihui; Qin, Jing; Liu, Yong; Huang, Bingsheng; Chen, Hanwei

    2017-01-01

    Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging.

  13. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies.

    Science.gov (United States)

    Gangadaran, Prakash; Ahn, Byeong-Cheol

    2017-01-01

    Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK) cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  14. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies

    Directory of Open Access Journals (Sweden)

    Prakash Gangadaran

    2017-09-01

    Full Text Available Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  15. Molecular markers in breast cancer: new tools in imaging and prognosis

    OpenAIRE

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluorescent labeled (NIRF) tracers for detection of breast cancer. Thus far, only a few molecular imaging tracers have been taken to the clinic of which most are suitable for PET. My thesis describes the e...

  16. Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma.

    Science.gov (United States)

    Kalimuthu, Senthilkumar; Jeong, Ju Hye; Oh, Ji Min; Ahn, Byeong-Cheol

    2017-07-27

    Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer therapies in preclinical or clinical models are essential and the multimodal molecular imaging approach may represent a new stage for pharmacologic development in cancer. Monitoring the progress of lymphoma therapy with imaging modalities will help patients. Identifying and addressing key challenges is essential for successful integration of molecular imaging into the drug development process. In this review, we highlight the general usefulness of molecular imaging in drug development and radionuclide-based reporter genes. Further, we discuss the different molecular imaging modalities for lymphoma therapy and their preclinical and clinical applications.

  17. Molecular imaging of HER2-positive breast cancer: a step toward an individualized 'image and treat' strategy

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...

  18. Molecular imaging of HER2-positive breast cancer: a step toward an individualized 'image and treat' strategy

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...... individual approaches to targeted therapy of HER2-positive breast cancers....

  19. Assessment of subclinical atherosclerosis using contrast-enhanced ultrasound.

    Science.gov (United States)

    van den Oord, Stijn C H; ten Kate, Gerrit L; Akkus, Zeynettin; Renaud, Guillaume; Sijbrands, Eric J G; ten Cate, Folkert J; van der Lugt, Aad; Bosch, Johan G; de Jong, Nico; van der Steen, Antonius F W; Schinkel, Arend F L

    2013-01-01

    The sensitivity of standard carotid ultrasound and colour Doppler for the detection of subclinical atherosclerotic plaques is suboptimal. The aim of this study is to assess whether contrast-enhanced ultrasound (CEUS) added to standard carotid ultrasound improves the detection of subclinical atherosclerosis. Carotid intima-media thickness (CIMT) measurement, standard carotid ultrasound including colour Doppler imaging, and CEUS were performed in 100 asymptomatic patients with one or more risk factors for atherosclerosis. CEUS was performed using intravenous administration of SonoVue™ contrast agent (Bracco S.p.A., Milan, Italy). CIMT, standard ultrasound, colour Doppler, and CEUS were reviewed by two independent observers. Standard ultrasound, colour Doppler, and CEUS were scored for the presence of atherosclerotic plaques. Subclinical atherosclerosis was diagnosed if patients had a CIMT above their age-corrected threshold value or if atherosclerotic plaques were present on standard carotid ultrasound clips or CEUS clips. McNemar's test was performed to compare between groups. Twenty-one patients (21%) had a thickened CIMT value and were considered to have subclinical atherosclerosis. Standard carotid ultrasound including colour Doppler demonstrated atherosclerotic plaques in 77 patients (77%). The addition of CEUS to the standard ultrasound protocol demonstrated atherosclerotic plaques in 88 patients (88%). The incorporation of CEUS into the standard carotid ultrasound protocol resulted in a significantly improved detection of patients with subclinical atherosclerosis (P subclinical atherosclerosis in the carotid arteries. Atherosclerotic plaques which were only detected with CEUS and not with standard carotid ultrasound and colour Doppler imaging were predominantly hypoechoic.

  20. Molecular Imaging of Transporters with Positron Emission Tomography

    Science.gov (United States)

    Antoni, Gunnar; Sörensen, Jens; Hall, Håkan

    Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug

  1. Radiolabelled nanoparticles: novel classification of radiopharmaceuticals for molecular imaging of cancer.

    Science.gov (United States)

    Mirshojaei, Seyedeh Fatemeh; Ahmadi, Amirhossein; Morales-Avila, Enrique; Ortiz-Reynoso, Mariana; Reyes-Perez, Horacio

    2016-01-01

    Nanotechnology has been used for every single modality in the molecular imaging arena for imaging purposes. Synergic advantages can be explored when multiple molecular imaging modalities are combined with respect to single imaging modalities. Multifunctional nanoparticles have large surface areas, where multiple functional moieties can be incorporated, including ligands for site-specific targeting and radionuclides, which can be detected to create 3D images. Recently, radiolabeled nanoparticles with individual properties have attracted great interest regarding their use in multimodality tumor imaging. Multifunctional nanoparticles can combine diagnostic and therapeutic capabilities for both target-specific diagnosis and the treatment of a given disease. The future of nanomedicine lies in multifunctional nanoplatforms that combine the diagnostic ability and therapeutic effects using appropriate ligands, drugs, responses and technological devices, which together are collectively called theranostic drugs. Co-delivery of radiolabeled nanoparticles is useful in multifunctional molecular imaging areas because it comprises several advantages based on nanoparticles architecture, pharmacokinetics and pharmacodynamic properties.

  2. Tumor functional and molecular imaging utilizing ultrasound and ultrasound-mediated optical techniques.

    Science.gov (United States)

    Yuan, Baohong; Rychak, Joshua

    2013-02-01

    Tumor functional and molecular imaging has significantly contributed to cancer preclinical research and clinical applications. Among typical imaging modalities, ultrasonic and optical techniques are two commonly used methods; both share several common features such as cost efficiency, absence of ionizing radiation, relatively inexpensive contrast agents, and comparable maximum-imaging depth. Ultrasonic and optical techniques are also complementary in imaging resolution, molecular sensitivity, and imaging space (vascular and extravascular). The marriage between ultrasonic and optical techniques takes advantages of both techniques. This review introduces tumor functional and molecular imaging using microbubble-based ultrasound and ultrasound-mediated optical imaging techniques. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. MARS spectral molecular imaging of lamb tissue: data collection and image analysis

    CERN Document Server

    Aamir, R; Bateman, C.J.; Butler, A.P.H.; Butler, P.H.; Anderson, N.G.; Bell, S.T.; Panta, R.K.; Healy, J.L.; Mohr, J.L.; Rajendran, K.; Walsh, M.F.; Ruiter, N.de; Gieseg, S.P.; Woodfield, T.; Renaud, P.F.; Brooke, L.; Abdul-Majid, S.; Clyne, M.; Glendenning, R.; Bones, P.J.; Billinghurst, M.; Bartneck, C.; Mandalika, H.; Grasset, R.; Schleich, N.; Scott, N.; Nik, S.J.; Opie, A.; Janmale, T.; Tang, D.N.; Kim, D.; Doesburg, R.M.; Zainon, R.; Ronaldson, J.P.; Cook, N.J.; Smithies, D.J.; Hodge, K.

    2014-01-01

    Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we ...

  4. Molecular imaging of small animals with fluorescent proteins: from projection to multimodality.

    Science.gov (United States)

    Yang, Xiaoquan; Gong, Hui; Fu, Jianwei; Quan, Guotao; Huang, Chuan; Luo, Qingming

    2012-06-01

    Fluorescent proteins (FPs) have been widely adopted in cell research for protein trafficking and reporter gene expression studies, as well as to study other biological processes. However, biological tissue has high light scattering and high absorption coefficients of visible light; hence, using FPs in small animal imaging remains a challenge, especially when the FPs are located deep in the tissue. In small animals, fluorescence molecular imaging could potentially address this difficulty. We constructed fluorescence molecular imaging systems that have two modes: a planner mode (projection imaging) and a multimodality mode (fluorescence molecular tomography and micro-CT). The planner mode can provide projection images of a fluorophore in the whole body of a small animal, whereas three-dimensional information can be offered by multimodality mode. The planner imaging system works in the reflection mode and is designed to provide fast imaging. The multimodality imaging system is designed to allow quantification and three-dimensional localization of fluorophores. A nude mouse with a tumour targeted with a far-red FP, which is appropriate for in vivo imaging, was adopted to validate the two systems. The results indicate that the planner imaging system is probably suitable for high throughput molecular imaging, whereas the multimodality imaging system is fit for quantitative research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Optical molecular imaging of hypoxic breast cancer - From prospect to preclinical practice

    NARCIS (Netherlands)

    van Brussel, A.S.A.

    2013-01-01

    Current imaging modalities for breast cancer diagnosis and therapy monitoring either lack sensitivity, specificity, make use of radiation and/or give images of limited resolution. Optical molecular imaging is a novel technique that detects light emitted by (breast)cancer-specific probes with a

  6. Applications of the Preclinical Molecular Image in Biomedicine; Aplicaciones de la imagen Molecular Preclínica en Biomedicina

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, M.; Bascuñana, P.; Fernández de la Rosa, R.; De Cristobal, J.; García-García, L.; Pozo, M.A.

    2014-07-01

    Molecular imaging is a broad platform, which provides valuable information about physiological and pathophysiological changes in living organisms by non-invasive methods. Depending on the used technique: anatomical, functional metabolic or molecular data could be assessed. Positron Emission Tomography (PET) provides with functional and molecular data, and combined with Computerized Tomography (CT) and Magnetic Resonance (MRI) with the multimodality equipment, it can be exponentially improved. Metabolic pathways and changes on the molecular and cellular level are target in molecular imaging cancer research. Tumour microenvironment, stroma and new vessels can be assessed by PET imaging. Additionally the visualization of functions and monitoring data of provided therapies could be obtained. The aim of the current review is to summarize principles and novel findings in molecular imaging specifically in PET and its application in preclinical cancer research. The theoretical background of techniques and main applications will be highlighted [Spanish] La imagen molecular aporta información muy valiosa, mediante métodos no invasivos, acerca de la fisiología de organismos vivos y sus cambios debidos a patologías. Dependiendo de la técnica utilizada se pueden obtener datos anatómicos, funcionales, metabólicos o moleculares. La Tomografía por Emisión de Positrones (PET) aporta datos metabólicos y moleculares con una alta sensibilidad, y en asociación con la Tomografía Computarizada (TC) o con Resonancia Magnética (RM), con la aparición de los nuevos equipos multimodalidad, las posibilidades de diagnóstico se incrementan exponencialmente. La imagen molecular en investigación oncológica presenta como objetivos principales identificar las diferentes vías metabólicas tumorales y sus cambios a nivel molecular y celular, el comportamiento del microentorno tumoral, aparición de nuevos vasos, estroma, etc. Además, es posible el análisis y cuantificación del

  7. A CZT-based blood counter for quantitative molecular imaging.

    Science.gov (United States)

    Espagnet, Romain; Frezza, Andrea; Martin, Jean-Pierre; Hamel, Louis-André; Lechippey, Laëtitia; Beauregard, Jean-Mathieu; Després, Philippe

    2017-12-01

    Robust quantitative analysis in positron emission tomography (PET) and in single-photon emission computed tomography (SPECT) typically requires the time-activity curve as an input function for the pharmacokinetic modeling of tracer uptake. For this purpose, a new automated tool for the determination of blood activity as a function of time is presented. The device, compact enough to be used on the patient bed, relies on a peristaltic pump for continuous blood withdrawal at user-defined rates. Gamma detection is based on a 20 × 20 × 15 mm3 cadmium zinc telluride (CZT) detector, read by custom-made electronics and a field-programmable gate array-based signal processing unit. A graphical user interface (GUI) allows users to select parameters and easily perform acquisitions. This paper presents the overall design of the device as well as the results related to the detector performance in terms of stability, sensitivity and energy resolution. Results from a patient study are also reported. The device achieved a sensitivity of 7.1 cps/(kBq/mL) and a minimum detectable activity of 2.5 kBq/ml for 18F. The gamma counter also demonstrated an excellent stability with a deviation in count rates inferior to 0.05% over 6 h. An energy resolution of 8% was achieved at 662 keV. The patient study was conclusive and demonstrated that the compact gamma blood counter developed has the sensitivity and the stability required to conduct quantitative molecular imaging studies in PET and SPECT.

  8. Prevention and Regression of Atherosclerosis: Emerging Treatments

    Directory of Open Access Journals (Sweden)

    Aliosvi Rodríguez Rodríguez

    2014-06-01

    Full Text Available Occlusive vascular diseases such as acute coronary syndrome, cerebral stroke, and peripheral arterial disease, represent a serious health problem worldwide. In recent decades, there has been significant progress in the diagnosis and treatment of atherosclerosis. Intravascular ultrasound imaging provides detailed information on the anatomy of the plaque and it has been used in several studies to evaluate the results. Atherosclerosis destabilizes the normal protective mechanism provided by the endothelium and this mechanism has been involved in the pathophysiology of acute coronary disease and brain stroke. Main efforts focus on prevention, especially at early ages. This paper is a review of 68 updated bibliographic citations in order to show the current options available for the prevention and reversal of the atherosclerotic process.

  9. Near-infrared molecular probes for in vivo imaging.

    Science.gov (United States)

    Zhang, Xuan; Bloch, Sharon; Akers, Walter; Achilefu, Samuel

    2012-04-01

    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.

  10. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury.

    Science.gov (United States)

    Hoyt, Kenneth; Warram, Jason M; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2015-12-01

    The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. A population of rats underwent 30 min of renal ischemia (acute kidney injury, N = 6) or sham injury (N = 4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted.

  11. Molecular Imaging by Optically Detected Electron Spin Resonance of Nitrogen-Vacancies in Nanodiamonds

    Science.gov (United States)

    Hegyi, Alex; Yablonovitch, Eli

    2013-03-01

    Molecular imaging refers to a class of noninvasive biomedical imaging techniques with the sensitivity and specificity to image biochemical variations in-vivo. An ideal molecular imaging technique visualizes a biochemical target according to a range of criteria, including high spatial and temporal resolution, high contrast relative to non-targeted tissues, depth-independent penetration into tissue, lack of harm to the organism under study, and low cost. Because no existing molecular imaging modality is ideal for all purposes, new imaging approaches are needed. Here we demonstrate a novel molecular imaging approach, called nanodiamond imaging, that uses nanodiamonds containing nitrogen-vacancy (NV) color centers as an imaging agent, and image nanodiamond targets in pieces of chicken breast. Nanodiamonds can be tagged with biologically active molecules so they bind to specific receptors; their distribution can then be quantified in-vivo via optically-detected magnetic resonance of the NVs. In effect, we are demonstrating Optically-Detected Functional-Electron-Spin-Resonance-Imaging, OD-f-ESRI. By combining optical detection with magnetic resonance, nanodiamond imaging achieves high sensitivity and high spatial resolution. It is absent of the complications of ionizing radiation, and the cost should be similar to all-optical imaging. Because nanodiamond imaging is limited by the depth of optical penetration into tissue to depths of a few cm, nanodiamond imaging should open up new avenues of investigation for applications where high depth penetration is not required, such as in small-animal imaging, tumor margin imaging, sentinel lymph node mapping, and perhaps mammography.

  12. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Science.gov (United States)

    Meng, Qingqing; Li, Zheng

    2013-01-01

    Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained. PMID:23533377

  13. Investigating Atmospheric Oxidation with Molecular Dynamics Imaging and Spectroscopy

    Science.gov (United States)

    Merrill, W. G.; Case, A. S.; Keutsch, F. N.

    2013-06-01

    Volatile organic compounds (VOCs) in the Earth's atmosphere constitute trace gas species emitted primarily from the biosphere, and are the subject of inquiry for a variety of air quality and climate studies. Reactions intiated (primarily) by the hydroxyl radical (OH) lead to a myriad of oxygenated species (OVOCs), which in turn are prone to further oxidation. Investigations of the role that VOC oxidation plays in tropospheric chemistry have brought to light two troubling scenarios: (1) VOCs are responsible in part for the production of two EPA-regulated pollutants---tropospheric ozone and organic aerosol---and (2) the mechanistic details of VOC oxidation remain convoluted and poorly understood. The latter issue hampers the implementation of near-explicit atmospheric simulations, and large discrepancies in OH reactivity exist between measurements and models at present. Such discrepancies underscore the need for a more thorough description of VOC oxidation. Time-of-flight measurements and ion-imaging techniques are viable options for resolving some of the mechanistic and energetic details of VOC oxidation. Molecular beam studies have the advantage of foregoing unwanted bimolecular reactions, allowing for the characterization of specific processes which must typically compete with the complex manifold of VOC oxidation pathways. The focus of this work is on the unimolecular channels of organic peroxy radical intermediates, which are necessarily generated during VOC oxidation. Such intermediates may isomerize and decompose into distinct chemical channels, enabling the unambiguous detection of each pathway. For instance, a (1 + 1') resonance enhanced multiphoton ionization (REMPI) scheme may be employed to detect carbon monoxide generated from a particular unimolecular process. A number of more subtle mechanistic details may be explored as well. By varying the mean free path of the peroxy radicals in a flow tube, the role of collisional quenching in these unimolecular

  14. Handbook of nuclear medicine and molecular imaging principles and clinical applications

    CERN Document Server

    Kim, Edmund E; Tateishi, Ukihide; Baum, Richard P

    2012-01-01

    This handbook will provide updated information on nuclear medicine and molecular imaging techniques as well as its clinical applications, including radionuclide therapy, to trainees and practitioners of nuclear medicine, radiology and general medicine. Updated information on nuclear medicine and molecular imaging are vitally important and useful to both trainees and existing practitioners. Imaging techniques and agents are advancing and changing so rapidly that concise and pertinent information are absolutely necessary and helpful. It is hoped that this handbook will help readers be better equipped for the utilization of new imaging methods and treatments using radiopharmaceuticals.

  15. Half-time Tc-99m sestamibi imaging with a direct conversion molecular breast imaging system.

    Science.gov (United States)

    Hruska, Carrie B; Conners, Amy Lynn; Jones, Katie N; Weinmann, Amanda L; Lingineni, Ravi K; Carter, Rickey E; Rhodes, Deborah J; O'Connor, Michael K

    2014-01-15

    In an effort to reduce necessary acquisition time to perform molecular breast imaging (MBI), we compared diagnostic performance of MBI performed with standard 10-min-per-view acquisitions and half-time 5-min-per-view acquisitions, with and without wide beam reconstruction (WBR) processing. Eighty-two bilateral, two-view MBI studies were reviewed. Studies were performed with 300 MBq Tc-99 m sestamibi and a direct conversion molecular breast imaging (DC-MBI) system. Acquisitions were 10 min-per-view; the first half of each was extracted to create 5-min-per-view datasets, and WBR processing was applied.The 10-min-, 5-min-, and 5-min-per-view WBR studies were independently interpreted in a randomized, blinded fashion by two radiologists. Assessments of 1 to 5 were assigned; 4 and 5 were considered test positive. Background parenchymal uptake, lesion type, distribution of non-mass lesions, lesion intensity, and image quality were described. Considering detection of all malignant and benign lesions, 5 min-per-view MBI had lower sensitivity (mean of 70% vs. 85% (p ≤ 0.04) for two readers) and lower area under curve (AUC) (mean of 92.7 vs. 99.6, p ≤ 0.01) but had similar specificity (p = 1.0). WBR processing did not alter sensitivity, specificity, or AUC obtained at 5 min-per-view.Overall agreement in final assessment between 5-min-per-view and 10-min-per-view acquisition types was near perfect (κ = 0.82 to 0.89); however, fair to moderate agreement was observed for assessment category 3 (probably benign) (κ = 0.24 to 0.48). Of 33 malignant lesions, 6 (18%) were changed from assessment of 4 or 5 with 10-min-per-view MBI to assessment of 3 with 5-min-per-view MBI. Image quality of 5-min-per-view studies was reduced compared to 10-min-per-view studies for both readers (3.24 vs. 3.98, p < 0.0001 and 3.60 vs. 3.91, p < 0.0001). WBR processing improved image quality for one reader (3.85 vs. 3.24, p < 0.0001). Although similar

  16. Molecular Imaging : Computer Reconstruction and Practice - Proceedings of the NATO Advanced Study Institute on Molecular Imaging from Physical Principles to Computer Reconstruction and Practice

    CERN Document Server

    Lemoigne, Yves

    2008-01-01

    This volume collects the lectures presented at the ninth ESI School held at Archamps (FR) in November 2006 and is dedicated to nuclear physics applications in molecular imaging. The lectures focus on the multiple facets of image reconstruction processing and management and illustrate the role of digital imaging in clinical practice. Medical computing and image reconstruction are introduced by analysing the underlying physics principles and their implementation, relevant quality aspects, clinical performance and recent advancements in the field. Several stages of the imaging process are specifically addressed, e.g. optimisation of data acquisition and storage, distributed computing, physiology and detector modelling, computer algorithms for image reconstruction and measurement in tomography applications, for both clinical and biomedical research applications. All topics are presented with didactical language and style, making this book an appropriate reference for students and professionals seeking a comprehen...

  17. Towards molecular imaging and treatment of disease with radionuclides: the role of inorganic chemistry.

    Science.gov (United States)

    Blower, Phil

    2006-04-14

    Molecular imaging and radiotherapy using radionuclides is a rapidly expanding field of medicine and medical research. This article highlights the development of the role of inorganic chemistry in designing and producing the radiopharmaceuticals on which this interdisciplinary science depends.

  18. Neurobiological mechanisms of treatment resistant depression: Functional, structural and molecular imaging studies

    NARCIS (Netherlands)

    de Kwaasteniet, B.P.

    2015-01-01

    This thesis investigated the neurobiological mechanisms of TRD using functional, structural and molecular imaging studies. First the neurobiological mechanisms of MDD were investigated and revealed decreased functional connectivity between the ventral and dorsal network. Thereafter, structural

  19. Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

    NARCIS (Netherlands)

    Deddens, L.H.; Van Tilborg, G.A.F.; Mulder, W.J.M.; de Vries, H.E.; Dijkhuizen, R.M.

    2012-01-01

    Cellular and molecular magnetic resonance imaging (MRI) strategies for studying the spatiotemporal profile of neuroinflammatory processes after stroke are increasingly being explored since the first reports appeared about a decade ago. These strategies most often employ (super)paramagnetic contrast

  20. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    Science.gov (United States)

    2007-07-01

    tiny calcium deposits that 82 indicate changes within the breast possibly point- 83 ing to cancer . Microcalcifications especially are 84 usually...NUMBER A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques 5b. GRANT NUMBER W81XWH-05-1-0291 5c. PROGRAM...assistant were further trained in molecular imaging of breast cancer through seminars and workshops, and are currently conducting two research projects

  1. Dynamic fluorescence imaging with molecular agents for cancer detection

    Science.gov (United States)

    Kwon, Sun Kuk

    Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electron-multiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual

  2. A Role of the Bile Salt Receptor FXR in Atherosclerosis

    NARCIS (Netherlands)

    Hageman, Jurre; Herrema, Hilde; Groen, Albert K.; Kuipers, Folkert

    This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly

  3. A Role of the Bile Salt Receptor FXR in Atherosclerosis

    NARCIS (Netherlands)

    Hageman, J.; Herrema, H.J.; Groen, A.K.; Kuipers, F.

    2010-01-01

    This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly

  4. Molecular targeted therapy in modern oncology: Imaging assessment of treatment response and toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B. [Dept. of of Imaging, Dana Farber Cancer Institute, Boston (United States)

    2017-01-15

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

  5. Calix[4]arenes as Molecular Platforms in Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Schühle, D.T.

    2009-01-01

    Magnetic resonance imaging (MRI) is an important tool in medical diagnosis. It uses non-ionizing radio-frequency radiation and produces images with excellent resolution. To increase the contrast, Gd(III)-containing compounds are applied leading to a brightening of the area of interest. The

  6. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Foppa Murilo

    2001-01-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  7. Molecular Cancer Imaging with Polymeric Nanoassemblies: From Tumor Detection to Theranostics.

    Science.gov (United States)

    Mi, Peng; Wang, Fang; Nishiyama, Nobuhiro; Cabral, Horacio

    2017-01-01

    Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Molecular markers in breast cancer: new tools in imaging and prognosis

    NARCIS (Netherlands)

    Vermeulen, J.F.|info:eu-repo/dai/nl/338877169

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared

  9. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

    NARCIS (Netherlands)

    Mulder, Willem J. M.; Strijkers, Gustav J.; van Tilborg, Geralda A. F.; Griffioen, Arjan W.; Nicolay, Klaas

    2006-01-01

    In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the

  10. Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma

    NARCIS (Netherlands)

    Tummers, W.S. (Willemieke S.); A. Fariña-Sarasqueta (Arantza); M.C. Boonstra (M.); Prevoo, H.A. (Hendrica A.); C.F.M. Sier (Cornelis); J.S.D. Mieog (Sven); H. Morreau (Hans); C.H.J. van Eijck (Casper); P.J.K. Kuppen (P. J K); C.J.H. van de Velde (Cornelis); B.A. Bonsing (Bert); A.L. Vahrmeijer (Alexander L.); Swijnenburg, R.-J. (Rutger-Jan)

    2017-01-01

    textabstractDiscrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this

  11. Molecular and Functional Imaging for Detection of Lymph Node Metastases in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ansje Fortuin

    2013-07-01

    Full Text Available Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node metastases. Therefore, there is a need for more accurate non-invasive diagnostic techniques. Molecular and functional imaging has been subject of research for the last decades, in this respect. Therefore, in this article the value of imaging techniques to detect lymph node metastases is reviewed. These techniques include scintigraphy, sentinel node imaging, positron emission tomography/computed tomography (PET/CT, diffusion weighted magnetic resonance imaging (DWI MRI and magnetic resonance lymphography (MRL. Knowledge on pathway and size of lymph node metastases has increased with molecular and functional imaging. Furthermore, improved detection and localization of lymph node metastases will enable (focal treatment of the positive nodes only.

  12. Spying on cancer: molecular imaging in vivo with genetically encoded reporters.

    Science.gov (United States)

    Gross, Shimon; Piwnica-Worms, David

    2005-01-01

    Genetically encoded imaging reporters introduced into cells and transgenic animals enable noninvasive, longitudinal studies of dynamic biological processes in vivo. The most common reporters include firefly luciferase (bioluminescence imaging), green fluorescence protein (fluorescence imaging), herpes simplex virus-1 thymidine kinase (positron emission tomography), and variants with enhanced spectral and kinetic properties. When cloned into promoter/enhancer sequences or engineered into fusion proteins, imaging reporters allow transcriptional regulation, signal transduction, protein-protein interactions, oncogenic transformation, cell trafficking, and targeted drug action to be spatiotemporally resolved in vivo. Spying on cancer with genetically encoded imaging reporters provides insight into cancer-specific molecular machinery within the context of the whole animal.

  13. Molecular Probes for Imaging of Hypoxia in the Retina

    OpenAIRE

    Evans, Stephanie M.; Kim, Kwangho; Moore, Chauca E.; Uddin, Md Imam; Capozzi, Megan E.; Craft, Jason R.; Gary A Sulikowski; Jayagopal, Ashwath

    2014-01-01

    Hypoxia has been associated with retinal diseases which lead the causes of irreversible vision loss, including diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. Therefore, technologies for imaging hypoxia in the retina are needed for early disease detection, monitoring of disease progression, and assessment of therapeutic responses in the patient. Toward this goal, we developed two hypoxia-sensitive imaging agents based on nitroimidazoles which are capabl...

  14. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer.

    Science.gov (United States)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n=128) were retraction phenomenon (odds ratio [OR]=10.188), post-acoustic shadowing (OR=5.112), and echogenic halo (OR=3.263, Pimaging features, especially retraction phenomenon, have a strong correlation with the molecular subtypes, expanding the scope of ultrasound in identifying breast cancer subtypes with confidence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Autonomic innervation of the heart. Role of molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Slart, Riemer H.J.A; Elsinga, Philip H. [Univ. Medical Center Groningen (Netherlands). Nuclear Medicine and Molecular Imaging; Tio, Rene A. [Univ. Medical Center Groningen (Netherlands). Thorax Center Cardiology; Schwaiger, Markus (ed.) [Technische Univ. Muenchen Klinikum Rechts der Isar (Germany). Nuklearmedizinische Klinik

    2015-03-01

    Reviews in detail the value of SPECT-CT and PET-CT in the imaging of cardiac innervation. Details the role of imaging in a range of conditions and diseases. Includes important background on pathophysiology, tracers, radiopharmaceutical production, and kinetic modeling software. This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

  16. Multimodality molecular imaging of disease progression in living ...

    Indian Academy of Sciences (India)

    2011-08-07

    Aug 7, 2011 ... ... events from single live cells to whole animals with high sensitivity and accurate quantification are discussed. Such approaches have immense potential to track progression of metastasis, immune cell trafficking, stem cell therapy, transgenic animals and even molecular interactions in living subjects.

  17. ABC Transporters, Atherosclerosis and Inflammation

    OpenAIRE

    Fitzgerald, Michael L.; Mujawar, Zahedi; Tamehiro, Norimasa

    2010-01-01

    Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangi...

  18. Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis

    NARCIS (Netherlands)

    A.F.L. Schinkel (Arend); M. Kaspar (Mathias); D. Staub (Daniel)

    2016-01-01

    textabstractContrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate patients with known or suspected atherosclerosis. The administration of a microbubble contrast agent in conjunction with ultrasound results in an improved image quality and provides information that cannot be

  19. Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ernesto Oviedo-Orta

    2008-06-01

    Full Text Available Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs, beta2glycoprotein1 (β2GP1, lipoprotein a (LP(a, heat shock proteins (HSPs, and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques.

  20. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  1. Intraoperative Molecular Imaging for Rapid Assessment of Tumor Margins

    Science.gov (United States)

    2010-09-01

    determine the depth of embedded tumor fragments in the excise tissue or surgical cavity. Pilot animal data with the Licor IRDye800CW-2DG imaging agent in...and the tumor immediately removed with adjacent normal tissue. All tissue were soaked for 5 – 20 minutes in a solution of Licor IRDye800CW-2DG and... Licor IRDye800CW-2DG, showing a cross section of the tumor mass. These images show a significant amount of non-specific uptake of the probe in

  2. Assessment of Residual Disease With Molecular Breast Imaging in Patients Undergoing Neoadjuvant Therapy: Association With Molecular Subtypes.

    Science.gov (United States)

    Menes, Tehillah S; Golan, Orit; Vainer, Gilead; Lerman, Hedva; Schneebaum, Schlomo; Klausner, Joseph; Even-Sapir, Einat

    2016-10-01

    Assessment of residual disease after neoadjuvant therapy for breast cancer is an ongoing challenge of breast imaging. This study evaluates the accuracy of a novel dedicated system for molecular breast imaging (MBI) composed of the new generation of cadmium zinc telluride detectors in assessing residual disease after neoadjuvant therapy in patients with breast cancer. Clinical data, imaging, surgical, and pathological findings of 51 women with breast cancer undergoing neoadjuvant therapy were recorded. MBI findings were correlated with surgical pathology results. Accuracy of MBI in predicting complete pathological response and size of residual disease was assessed according to molecular subtypes. The size of the largest focus of uptake on MBI correlated with the largest dimension measured on pathology (r = 0.55; P < .001). This correlation was stronger for triple negative and HER2/neu positive subtypes (r = 0.92 and 0.62, respectively). Sixteen patients (31%) had complete pathological response. The sensitivity and specificity of MBI for detecting residual disease were 83% (95% confidence interval [CI], 66-93) and 69% (95% CI, 42-88), respectively. For triple negative or HER2/neu positive disease the sensitivity and specificity were 88% (95% CI, 62-98) and 75% (95% CI, 43-93), respectively. The accuracy of MBI in assessing residual disease after neoadjuvant treatment might be related to the molecular subtype. Accuracy is highest in the triple negative and HER2/neu positive subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Recent advances and clinical insights into the use of proteomics in the study of atherosclerosis.

    Science.gov (United States)

    Mourino-Alvarez, Laura; Baldan-Martin, Montserrat; Rincon, Raul; Martin-Rojas, Tatiana; Corbacho-Alonso, Nerea; Sastre-Oliva, Tamara; Barderas, Maria G

    2017-08-01

    The application of new proteomics methods may help to identify new diagnostic/predictive molecular markers in an attempt to improve the clinical management of atherosclerosis. Areas covered: Technological advances in proteomics have enhanced its sensitivity and multiplexing capacity, as well as the possibility of studying protein interactions and tissue structure. These advances will help us better understand the molecular mechanisms at play in atherosclerosis as a biological system. Moreover, this should help identify new predictive/diagnostic biomarkers and therapeutic targets that may facilitate effective risk stratification and early diagnosis, with the ensuing rapid implementation of treatment. This review provides a comprehensive overview of the novel methods in proteomics, including state-of-the-art techniques, novel biological samples and applications for the study of atherosclerosis. Expert commentary: Collaboration between clinicians and researchers is crucial to further validate and introduce new molecular markers to manage atherosclerosis that are identified using the most up to date proteomic approaches.

  4. Live Cell Imaging and Measurements of Molecular Dynamics

    Science.gov (United States)

    Frigault, M.; Lacoste, J.; Swift, J.; Brown, C.

    2010-01-01

    w3-2 Live cell microscopy is becoming widespread across all fields of the life sciences, as well as, many areas of the physical sciences. In order to accurately obtain live cell microscopy data, the live specimens must be properly maintained on the imaging platform. In addition, the fluorescence light path must be optimized for efficient light transmission in order to reduce the intensity of excitation light impacting the living sample. With low incident light intensities the processes under study should not be altered due to phototoxic effects from the light allowing for the long term visualization of viable living samples. Aspects for maintaining a suitable environment for the living sample, minimizing incident light and maximizing detection efficiency will be presented for various fluorescence based live cell instruments. Raster Image Correlation Spectroscopy (RICS) is a technique that uses the intensity fluctuations within laser scanning confocal images, as well as the well characterized scanning dynamics of the laser beam, to extract the dynamics, concentrations and clustering of fluorescent molecules within the cell. In addition, two color cross-correlation RICS can be used to determine protein-protein interactions in living cells without the many technical difficulties encountered in FRET based measurements. RICS is an ideal live cell technique for measuring cellular dynamics because the potentially damaging high intensity laser bursts required for photobleaching recovery measurements are not required, rather low laser powers, suitable for imaging, can be used. The RICS theory will be presented along with examples of live cell applications.

  5. Molecular Imaging of Cancer with Nanoparticle-Based Theranostic Probes

    Directory of Open Access Journals (Sweden)

    Ying-Yu Ma

    2017-01-01

    Full Text Available Although advancements in medical technology supporting cancer diagnosis and treatment have improved survival, these technologies still have limitations. Recently, the application of noninvasive imaging for cancer diagnosis and therapy has become an indispensable component in clinical practice. However, current imaging contrasts and tracers, which are in widespread clinical use, have their intrinsic limitations and disadvantages. Nanotechnologies, which have improved in vivo detection and enhanced targeting efficiency for cancer, may overcome some of the limitations of cancer diagnosis and therapy. Theranostic nanoparticles have great potential as a therapeutic model, which possesses the ability of their nanoplatforms to load targeted molecule for both imaging and therapeutic functions. The resulting nanosystem will likely be critical with the growth of personalized medicine because of their diagnostic potential, effectiveness as a drug delivery vehicle, and ability to oversee patient response to therapy. In this review, we discuss the achievements of modern nanoparticles with the goal of accurate tumor imaging and effective treatment and discuss the future prospects.

  6. Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes for Enhanced Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Juan Pellico

    2017-01-01

    Full Text Available The combination of the size-dependent properties of nanomaterials with radioisotopes is emerging as a novel tool for molecular imaging. There are numerous examples already showing how the controlled synthesis of nanoparticles and the incorporation of a radioisotope in the nanostructure offer new features beyond the simple addition of different components. Among the different nanomaterials, iron oxide-based nanoparticles are the most used in imaging because of their versatility. In this review, we will study the different radioisotopes for biomedical imaging, how to incorporate them within the nanoparticles, and what applications they can be used for. Our focus is directed towards what is new in this field, what the nanoparticles can offer to the field of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use in molecular imaging.

  7. Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

    Science.gov (United States)

    Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

    2014-05-01

    Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013

  8. Advancing Precision Nuclear Medicine and Molecular Imaging for Lymphoma.

    Science.gov (United States)

    Wright, Chadwick L; Maly, Joseph J; Zhang, Jun; Knopp, Michael V

    2017-01-01

    PET with fluorodeoxyglucose F 18 (18F FDG-PET) is a meaningful biomarker for the detection, targeted biopsy, and treatment of lymphoma. This article reviews the evolution of 18F FDG-PET as a putative biomarker for lymphoma and addresses the current capabilities, challenges, and opportunities to enable precision medicine practices for lymphoma. Precision nuclear medicine is driven by new imaging technologies and methodologies to more accurately detect malignant disease. Although quantitative assessment of response is limited, such technologies will enable a more precise metabolic mapping with much higher definition image detail and thus may make it a robust and valid quantitative response assessment methodology. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Eosinophilic cardiac disease: Molecular, clinical and imaging aspects.

    Science.gov (United States)

    Séguéla, Pierre-Emmanuel; Iriart, Xavier; Acar, Philippe; Montaudon, Michel; Roudaut, Raymond; Thambo, Jean-Benoit

    2015-04-01

    Eosinophilia may be responsible for cardiac injuries of widely varying severity, from acute myocarditis to endomyocardial fibrosis. In this review, we present both the molecular mechanisms that are responsible for these lesions and their clinical and paraclinical aspects. Numerous aetiologies can lead to severe eosinophilia, but these are mainly represented by hypersensitivity reactions, rheumatological diseases and hypereosinophilic syndrome. Because cardiac involvement may be extremely severe, echocardiography should be always performed in the context of eosinophilia and appropriate therapeutics should be started rapidly in order to limit the progression of the disease. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Pheochromocytoma and Paraganglioma: Current Functional and Future Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Elise M Blanchet

    2012-01-01

    Full Text Available Paragangliomas are neural crest-derived tumors, arising either from chromaffin sympathetic tissue (in adrenal, abdominal, intra-pelvic or thoracic paraganglia or from parasympathetic tissue (in head and neck paraganglia. They have a specific cellular metabolism, with the ability to synthesize, store and secrete catecholamines (although most head and neck paragangliomas do not secrete any catecholamines. This disease is rare and also very heterogeneous, with various presentations (e.g., in regards to localization, multifocality, potential to metastasize, biochemical phenotype, and genetic background. With growing knowledge, notably about the pathophysiology and genetic background, guidelines are evolving rapidly. In this context, functional imaging is a challenge for the management of paragangliomas.Nuclear imaging has been used for exploring paragangliomas for the last three decades, with MIBG historically as the first-line exam. Tracers used in paragangliomas can be grouped in three different categories. Agents that specifically target catecholamine synthesis, storage, and secretion pathways include: 123 and 131I-metaiodobenzylguanidine (123/131I-MIBG, 18F-fluorodopamine (18F-FDA, and 18F-fluorodihydroxyphenylalanine (18F-FDOPA. Agents that bind somatostatin receptors include 111In-pentetreotide and 68Ga-labelled somatostatin analog peptides. The non-specific agent most commonly used in paragangliomas is 18F-fluorodeoxyglucose (18F-FDG. This review will first describe conventional scintigraphic exams that are used for imaging paragangliomas. In the second part we will emphasize the interest in new PET approaches (specific and non-specific, considering the growing knowledge about genetic background and pathophysiology, with the aim of understanding how tumors behave, and optimally adjusting imaging technique for each tumor type.

  11. Insight into the Molecular Imaging of Alzheimer's Disease

    OpenAIRE

    Abishek Arora; Neeta Bhagat

    2016-01-01

    Alzheimer’s disease is a complex neurodegenerative disease affecting millions of individuals worldwide. Earlier it was diagnosed only via clinical assessments and confirmed by postmortem brain histopathology. The development of validated biomarkers for Alzheimer’s disease has given impetus to improve diagnostics and accelerate the development of new therapies. Functional imaging like positron emission tomography (PET), single photon emission computed tomography (SPECT), functional magnetic re...

  12. Strategies for molecular imaging dementia and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Bernhard J Schaller

    2008-06-01

    Full Text Available Bernhard J SchallerDepartment of Neurosurgery, University of Paris, Paris, FranceAbstract: Dementia represents a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathological changes during continuing degenerative disease of the brain. As such, there lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes in this disease process. But increasing this knowledge has given more insights into memory deterioration in patients suffering from Alzheimer’s disease and other subtypes of dementia. The author reviews current knowledge of the physiological coupling between cerebral blood flow and metabolism in the light of state-of-the-art-imaging methods and its changes in dementia with special reference to Alzheimer’s disease. Different imaging techniques are discussed with respect to their visualizing effect of biochemical, cellular, and/or structural changes in dementia. The pathophysiology of dementia in advanced age is becoming increasingly understood by revealing the underlying basis of neuropsychological changes with current imaging techniques, genetic and pathological features, which suggests that alterations of (neurovascular regulatory mechanisms may lead to brain dysfunction and disease. The current view is that cerebrovascular deregulation is seen as a contributor to cerebrovascular pathologies, such as stroke, but also to neurodegenerative conditions, such as Alzheimer’s disease. The better understanding of these (pathophysiological mechanisms may open an approach to new interventional strategies in dementia to enhance neurovascular repair and to protect neurovascular coupling.Keywords: imaging, cognitive impairment, Alzheimer’s disease, cerebrovascular disease, neurovascular coupling

  13. Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Congsen [LaserLaB Amsterdam, VU University Amsterdam, de Boelelaan 1083, 1081 HV Amsterdam (Netherlands); Department of Physics, National University of Defense Technology, Changsha 410073 (China); Janssen, Maurice H. M. [LaserLaB Amsterdam, VU University Amsterdam, de Boelelaan 1083, 1081 HV Amsterdam (Netherlands)

    2015-02-15

    Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the density profile of the molecular beam, and the measured absolute density is compared with theoretical calculations of the centre line beam density. Subsequently, we discuss reasons accounting for the differences between measurements and calculations and propose that strong skimmer interference is the most probable cause for the differences. Furthermore, we report on experiments measuring the centre line density of seeded supersonic beams. The femtosecond ion images show that seeding the heavy Xe atom at low relative seed fractions (1%-10%) in a light carrier gas like Ne results in strong relative enhancements of up to two orders of magnitude.

  14. Construction of specific magnetic resonance imaging/optical dual-modality molecular probe used for imaging angiogenesis of gastric cancer.

    Science.gov (United States)

    Yan, Xuejie; Song, Xiaoyan; Wang, Zhenbo

    2017-05-01

    The purpose of the study was to construct specific magnetic resonance imaging (MRI)/optical dual-modality molecular probe. Tumor-bearing animal models were established. MRI/optical dual-modality molecular probe was construed by coupling polyethylene glycol (PEG)-modified nano-Fe3O4 with specific targeted cyclopeptide GX1 and near-infrared fluorescent dyes Cy5.5. MRI/optical imaging effects of the probe were observed and the feasibility of in vivo double-modality imaging was discussed. It was found that, the double-modality probe was of high stability; tumor signal of the experimental group tended to be weak after injection of the probe, but rose to a level which was close to the previous level after 18 h (p > 0.05). We successively completed the construction of an ideal MRI/optical dual-modality molecular probe. MRI/optical dual-modality molecular probe which can selectively gather in gastric cancer is expected to be a novel probe used for diagnosing gastric cancer in the early stage.

  15. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy.

    Science.gov (United States)

    Tassa, Carlos; Shaw, Stanley Y; Weissleder, Ralph

    2011-10-18

    Advances in our understanding of the genetic basis of disease susceptibility coupled with prominent successes for molecular targeted therapies have resulted in an emerging strategy of personalized medicine. This approach envisions risk stratification and therapeutic selection based on an individual's genetic makeup and physiologic state (the latter assessed through cellular or molecular phenotypes). Molecularly targeted nanoparticles can play a key role in this vision through noninvasive assessments of molecular processes and specific cell populations in vivo, sensitive molecular diagnostics, and targeted delivery of therapeutics. A superparamagnetic iron oxide nanoparticle with a cross-linked dextran coating, or CLIO, is a powerful and illustrative nanoparticle platform for these applications. These structures and their derivatives support diagnostic imaging by magnetic resonance (MRI), optical, and positron emission tomography (PET) modalities and constitute a versatile platform for conjugation to targeting ligands. A variety of conjugation methods exist to couple the dextran surface to different functional groups; in addition, a robust bioorthogonal [4 + 2] cycloaddition reaction between 1,2,4,5-tetrazene (Tz) and trans-cyclooctene (TCO) can conjugate nanoparticles to targeting ligands or label pretargeted cells. The ready availability of conjugation methods has given rise to the synthesis of libraries of small molecule modified nanoparticles, which can then be screened for nanoparticles with specificity for a specific cell type. Since most nanoparticles display their targeting ligands in a multivalent manner, a detailed understanding of the kinetics and affinity of a nanoparticle's interaction with its target (as determined by surface plasmon resonance) can yield functionally important insights into nanoparticle design. In this Account, we review applications of the CLIO platform in several areas relevant to the mission of personalized medicine. We demonstrate

  16. Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

    Science.gov (United States)

    Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L; Bilello, Michel; O'Rourke, Donald M; Davatzikos, Christos

    2016-03-01

    MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Molecularly imprinted polymer-coated quantum dots for multiplexed cell targeting and imaging

    OpenAIRE

    Panagiotopoulou, Maria; Salinas, Yolanda; Beyazit, Selim; Kunath, Stephanie; Duma, Luminita; Prost, Elise; Mayes, Andrew G.; Resmini, Marina; Tse Sum Bui, Bernadette; Haupt, Karsten

    2016-01-01

    Advanced tools for cell imaging are of great interest to detect, localize and quantify molecular biomarkers of cancer or infection. We describe a novel photopolymerization method to coat quantum dots (QDs) with polymer shells, in particular molecularly imprinted polymers (MIPs), using the visible light emitted from QDs excited by UV light. Fluorescent core-shell particles specifically recognizing glucuronic acid (GlcA) or N-acetylneuraminic acid (NANA) were prepared. Simultaneous multiplexed ...

  18. Targeting the treatment of drug abuse with molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schiffer, Wynne K. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: wynne@bnl.gov; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2007-10-15

    Although imaging studies in and of themselves have significant contributions to the study of human behavior, imaging in drug abuse has a much broader agenda. Drugs of abuse bind to molecules in specific parts of the brain in order to produce their effects. Positron emission tomography (PET) provides a unique opportunity to track this process, capturing the kinetics with which an abused compound is transported to its site of action. The specific examples discussed here were chosen to illustrate how PET can be used to map the regional distribution and kinetics of compounds that may or may not have abuse liability. We also discussed some morphological and functional changes associated with drug abuse and different stages of recovery following abstinence. PET measurements of functional changes in the brain have also led to the development of several treatment strategies, one of which is discussed in detail here. Information such as this becomes more than a matter of academic interest. Such knowledge can provide the bases for anticipating which compounds may be abused and which may not. It can also be used to identify biological markers or changes in brain function that are associated with progression from drug use to drug abuse and also to stage the recovery process. This new knowledge can guide legislative initiatives on the optimal duration of mandatory treatment stays, promoting long-lasting abstinence and greatly reducing the societal burden of drug abuse. Imaging can also give some insights into potential pharmacotherapeutic targets to manage the reinforcing effects of addictive compounds, as well as into protective strategies to minimize their toxic consequences.

  19. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

  20. Imaging Multi-Particle Atomic and Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Landers, Allen [Auburn Univ., AL (United States)

    2016-02-12

    Final Report for Grant Number: DE- FG02-10ER16146 This grant supported research in basic atomic, molecular and optical physics related to the interactions of atoms and molecules with photons and electrons. The duration of the grant was the 5 year period from 4/1/2010 – 10/31/2015. All of the support from the grant was used to pay salaries of the PI, graduate students, and undergraduates and travel to conferences and meetings. The results were in the form of publications in peer reviewed journals. There were 20 peer reviewed publications over these 5 years with 2 of the publications in Physical Review Letters and 1 in Nature; all of the other articles were in respected peer reviewed journals (Physical Review A, New Journal of Physics, Journal of Physics B ...).

  1. Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

    Directory of Open Access Journals (Sweden)

    A. Greco

    2012-01-01

    Full Text Available Ultrasound biomicroscopy (UBM is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research.

  2. Recent Advance of Biological Molecular Imaging Based on Lanthanide-Doped Upconversion-Luminescent Nanomaterials

    Directory of Open Access Journals (Sweden)

    Yuanzeng Min

    2014-02-01

    Full Text Available Lanthanide-doped upconversion-luminescent nanoparticles (UCNPs, which can be excited by near-infrared (NIR laser irradiation to emit multiplex light, have been proven to be very useful for in vitro and in vivo molecular imaging studies. In comparison with the conventionally used down-conversion fluorescence imaging strategies, the NIR light excited luminescence of UCNPs displays high photostability, low cytotoxicity, little background auto-fluorescence, which allows for deep tissue penetration, making them attractive as contrast agents for biomedical imaging applications. In this review, we will mainly focus on the latest development of a new type of lanthanide-doped UCNP material and its main applications for in vitro and in vivo molecular imaging and we will also discuss the challenges and future perspectives.

  3. Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

    Directory of Open Access Journals (Sweden)

    Olugbenga T. Okusanya

    2015-01-01

    Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

  4. Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

    Science.gov (United States)

    Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

    2018-01-01

    Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

  5. Preclinical and clinical applications of specific molecular imaging for HER2-positive breast cancer.

    Science.gov (United States)

    Chen, Wei; Li, Xiaofeng; Zhu, Lei; Liu, Jianjing; Xu, Wengui; Wang, Ping

    2017-08-01

    Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2 (HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.

  6. Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

    OpenAIRE

    Greco, A.; Mancini, M.; Gargiulo, S; Gramanzini, M.; Claudio, P. P.; Brunetti, A; Salvatore, . M

    2011-01-01

    Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at ...

  7. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

    Science.gov (United States)

    2013-07-01

    4 hours followed by two washes in 50% methanol. Dried peptides were later dissolved in 0.1% formic acid for analysis by LC-MS/MS. Duplicate...FOLR1 protein is a folate receptor family member that binds folic acid and a number of reduced folic acid derivatives and transports 5...is to develop nanoparticle -based molecular imaging probes that can be used in conjunction with photoacoustic imaging (PAI) as an ovarian cancer early

  8. Macrovascular disease and atherosclerosis in SSc

    NARCIS (Netherlands)

    Hettema, M. E.; Bootsma, H.; Kallenberg, C. G. M.

    Atherosclerosis is considered to be a chronic inflammatory disorder. Several autoimmune rheumatic diseases are characterized by premature and accelerated atherosclerosis in which both classical and non-classical risk factors contribute to atherogenesis. SSc is characterized by vasculopathy, and

  9. Trained innate immunity and atherosclerosis.

    Science.gov (United States)

    Bekkering, Siroon; Joosten, Leo A B; van der Meer, Jos W M; Netea, Mihai G; Riksen, Niels P

    2013-12-01

    Monocytes/macrophages play a decisive role in the development and progression of atherosclerosis. It is currently unknown what stimuli initiate and orchestrate the activation of these cells in atherogenesis. In this review, we postulate that the novel concept of 'trained immunity' modulates the development and progression of atherosclerosis. Recently, results from our laboratory challenged the current paradigm that innate immunity is static and does not have an immunological memory. Stimulation by various microbial products, including Candida albicans and bacille Calmette-Guérin, appeared to bring monocytes into a long-term enhanced functional state, showing a stronger proinflammatory response to a second stimulus. This 'trained immunity' was mediated by increased and stable histone methylation. We describe the hypothesis that this functional reprogramming of monocytes, either by microbial products or by metabolic products, contributes to atherogenesis and propose epigenetic reprogramming of monocytes as a novel pharmacological target for preventing or treating atherosclerosis in the future.

  10. Final Technical Report for SISGR: Ultrafast Molecular Scale Chemical Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hersam, Mark C. [Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering; Guest, Jeffrey R. [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Guisinger, Nathan P. [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Hla, Saw Wai [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Schatz, George C. [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Seideman, Tamar [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Van Duyne, Richard P. [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry

    2017-04-10

    The Northwestern-Argonne SISGR program utilized newly developed instrumentation and techniques including integrated ultra-high vacuum tip-enhanced Raman spectroscopy/scanning tunneling microscopy (UHV-TERS/STM) and surface-enhanced femtosecond stimulated Raman scattering (SE-FSRS) to advance the spatial and temporal resolution of chemical imaging for the study of photoinduced dynamics of molecules on plasmonically active surfaces. An accompanying theory program addressed modeling of charge transfer processes using constrained density functional theory (DFT) in addition to modeling of SE-FSRS, thereby providing a detailed description of the excited state dynamics. This interdisciplinary and highly collaborative research resulted in 62 publications with ~ 48% of them being co-authored by multiple SISGR team members. A summary of the scientific accomplishments from this SISGR program is provided in this final technical report.

  11. Nanodiamond molecular imaging with enhanced contrast and expanded field of view

    Science.gov (United States)

    Hegyi, Alex; Yablonovitch, Eli

    2014-01-01

    Nanodiamond imaging is a new molecular imaging modality that takes advantage of nitrogen-vacancy (NV) centers in nanodiamonds to image a distribution of nanodiamonds with high sensitivity and high spatial resolution. Since nanodiamonds are nontoxic and are easily conjugated to biomolecules, nanodiamond imaging can potentially elicit physiological information from within a living organism. The position of the nanodiamonds is measured using optically detected electron spin resonance of the NVs. In a previous paper, we described a proof-of-principle nanodiamond imaging system with the ability to image in two dimensions over a 1×1 cm field of view and demonstrated imaging within scattering tissue. Here, we describe a second-generation nanodiamond imaging system with a field of view of 30×200 mm, and with three-dimensional imaging potential. The new system has a comparable spatial resolution of 1.2 mm FWHM and a sensitivity (in terms of the concentration of carbon atoms in a voxel) of 1.6 Hz, a 3-dB improvement relative to the old system. We show that imaging at 2.872 GHz versus imaging at 2.869 GHz offers a 1.73× improvement in sensitivity with only a 20% decrease in resolution and motivate this by describing the observed lineshape starting from the NV spin Hamiltonian.

  12. High-resolution, high sensitivity detectors for molecular imaging with radionuclides: The coded aperture option

    Energy Technology Data Exchange (ETDEWEB)

    Cusanno, F. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy)]. E-mail: francesco.cusanno@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Colilli, S. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Garibaldi, F. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Gricia, M. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lo Meo, S. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Santavenere, F. [Istituto Superiore di Sanita and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lanza, R.C. [Massachusetts Institute of Technology, Cambridge, MA (United States); Majewski, S. [Jefferson Lab, Newport News, 12000 Jefferson Avenue, 23606 VA (United States); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Orsini Cancelli, V. [INFN Sezione Roma III, Rome (Italy); De Notaristefani, F. [INFN Sezione Roma III, Rome (Italy); Bollini, D. [INFN Sezione di Bologna , Bologna (Italy); Navarria, F. [INFN Sezione di Bologna , Bologna (Italy); Moschini, G. [INFN Laboratori Nazionali di Legnaro, Legnaro (Italy)

    2006-12-20

    Molecular imaging with radionuclides is a very sensitive technique because it allows to obtain images with nanomolar or picomolar concentrations. This has generated a rapid growth of interest in radionuclide imaging of small animals. Indeed radiolabeling of small molecules, antibodies, peptides and probes for gene expression enables molecular imaging in vivo, but only if a suitable imaging system is used. Detecting small tumors in humans is another important application of such techniques. In single gamma imaging, there is always a well known tradeoff between spatial resolution and sensitivity due to unavoidable collimation requirements. Limitation of the sensitivity due to collimation is well known and affects the performance of imaging systems, especially if only radiopharmaceuticals with limited uptake are available. In many cases coded aperture collimation can provide a solution, if the near field artifact effect can be eliminated or limited. At least this is the case for 'small volumes' imaging, involving small animals. In this paper 3D-laminography simulations and preliminary measurements with coded aperture collimation are presented. Different masks have been designed for different applications showing the advantages of the technique in terms of sensitivity and spatial resolution. The limitations of the technique are also discussed.

  13. Molecular imaging using PET and SPECT for identification of breast cancer subtypes.

    Science.gov (United States)

    Liu, Hao; Chen, Yao; Wu, Shuang; Song, Fahuan; Zhang, Hong; Tian, Mei

    2016-11-01

    Breast cancer is a major disease with high morbidity and mortality in women. As a highly heterogeneous tumor, it contains different molecular subtypes: luminal A, luminal B, human epidermal growth factor 2-positive, and triple-negative subtypes. As each subtype has unique features, it may not be universal to the optimal treatment and expected response for individual patients. Therefore, it is critical to identify different breast cancer subtypes. Targeting subcellular levels, molecular imaging, especially PET and single photon emission computed tomography, has become a promising means to identify breast cancer subtypes and monitor treatment. Different biological processes between various subtypes, including changes correlated with receptor expression, cell proliferation, or glucose metabolism, have the potential for imaging with PET and single photon emission computed tomography radiopharmaceuticals. Receptor imaging, with radiopharmaceuticals targeting estrogen receptor, progesterone receptor, or human epidermal growth factor 2, is available to distinguish receptor-positive tumors from receptor-negative ones. Cell proliferation imaging with fluorine-18 fluorothymidine PET aids identification of luminal A and B subtypes on the basis of the correlation with the immunohistochemical biomarker Ki-67. Glucose metabolism imaging with fluorine-18 fluorodeoxyglucose PET may have potential to discriminate triple-negative subtypes from others. With increasing numbers of novel radiopharmaceuticals, noninvasive molecular imaging will be applied widely for the identification of different subtypes and provide more in-vivo information on individualized management of breast cancer patients.

  14. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Liang, E-mail: shanli@mail.nih.gov; Chopra, Arvind; Leung, Kam; Eckelman, William C. [National Institutes of Health, Molecular Imaging and Contrast Agent Database, National Center for Biotechnology Information, National Library of Medicine (United States); Menkens, Anne E. [National Institutes of Health, National Cancer Institute (United States)

    2012-09-15

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, {approx}4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

  15. Probiotics and atherosclerosis – a new challenge?

    Directory of Open Access Journals (Sweden)

    Chan Yee Kwan

    2012-06-01

    Full Text Available Background Atherosclerosis is the major cause of cardiovascular disease and stroke, which are among the top 10 leading causes of death worldwide. Pathogen-associated molecular patterns (PAMPs can activate toll-like receptors (TLRs and activate nuclear factor kappa B (NFκB signaling, a central pathway in inflammation, which regulates genes that encode proinflammatory molecules essential in atherogenesis. Lipopolysaccharides (LPS, which is unique to gram negative bacteria, as well as peptidoglycan (PGN, which is found in gram positive bacteria are PAMPS and ligands of TLR4 and TLR2, respectively, both of which are essential in plaque progression in atherosclerosis. Gastrointestinal tract is suggested to be the major site for absorption and translocation of TLR2 and TLR4 stimulants. Inflammation can result in a ‘leaky gut’ that leads to higher bacterial translocation, eventually the accumulation of LPS and PGN would activate TLRs and trigger inflammation through NFκB and promote further systemic complication like atherosclerosis. Probiotics, can protect the intestinal barrier to reduce bacterial translocation and have potential systemic anti-inflammatory properties.To evaluate whether probiotics can help reduce atherosclerotic development using in vivo study.Apolipoprotein E knockout (ApoE−/ −  mice were fed on high fat diet alone, with telmisartan (Tel (1 or 5 mg/kg/day, positive controls or with probiotics (VSL#3/LGG with or without Tel (1 mg/kg/day for 12 weeks.Probiotics, Tel, or a combination of both reduced lesion size at the aortic root significantly; VSL#3 reduced serum inflammatory adhesion molecules soluble E- (sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1, soluble vascular cell adhesion molecule 1 (sVCAM-1, and plaque disrupting factor matrix metalloproteinase (MMP-9 significantly; probiotics and Tel at 5 mg/kg/day could induce changes in gut microbiota population; the efficiency of lesion reduction seemed

  16. Relation of Framingham Risk Score to Subclinical Atherosclerosis Evaluated Across Three Arterial Sites

    Science.gov (United States)

    Karim, Roksana; Hodis, Howard N; Detrano, Robert; Liu, Chao-ran; Liu, Chi-hua; Mack, Wendy J

    2008-01-01

    The Framingham risk score (FRS) is widely used in clinical practice to identify subjects at high risk for developing coronary heart disease (CHD). However, FRS may not accurately identify subjects at risk. We measured subclinical atherosclerosis in the coronary arteries and aorta with the presence of calcium (CAC and AC, respectively) and in the common carotid artery by intima-media thickness (CIMT) in 498 healthy subjects. The distribution of these subclinical atherosclerosis measures was evaluated across 3 strata of the FRS. CAC, AC and CIMT were significantly independently associated with FRS. The FRS increased with the number of arterial sites with atherosclerosis. Sixty-nine percent of the subjects categorized in the low risk group (FRS20%) had 1 or more vascular imaging studies demonstrating subclinical atherosclerosis. Among the low risk group, subjects with atherosclerosis had a longer history of lifetime smoking compared to those without atherosclerosis. In conclusion, subclinical atherosclerosis is prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis in different arterial sites in addition to FRS may be useful in targeting subjects for lifestyle and other interventions. PMID:18805105

  17. Periodontal Innate Immune Mechanisms Relevant to Atherosclerosis

    OpenAIRE

    Amar, Salomon; Engelke, Marianne

    2014-01-01

    Atherosclerosis is a common cardiovascular disease in the United States. The disease is a leading cause of illness and death in the United States. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high-fat diet, obesity, high blood cholesterol levels, and smoking. However a sizable amount of patients suffering from atherosclerosis do not harbor the classical ...

  18. Long noncoding RNAs and atherosclerosis.

    Science.gov (United States)

    Zhou, Tian; Ding, Jia-wang; Wang, Xin-an; Zheng, Xia-xia

    2016-05-01

    Atherosclerosis is universally recognized as a chronic lipid-induced inflammation of the vessel wall in response to dyslipidemia and haemodynamic stress involving dysfunction and activation of resident vascular cells as well as infiltration of leukocytes. As members of nonprotein-coding RNAs, the long noncoding RNAs (lncRNAs) are implicated in various biological processes. Accumulating evidences suggest that lncRNAs regulate the function of vascular wall, activation of macrophages, lipid metabolism and immune response. Here, we review the effects of lncRNAs on the progress of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  20. Diagnostic Magnetic Resonance Imaging of Atherosclerosis in Apolipoprotein E Knockout Mouse Model Using Macrophage-Targeted Gadolinium-Containing Synthetic Lipopeptide Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Zu T Shen

    Full Text Available Cardiovascular disease is the leading cause of death in Western cultures. The vast majority of cardiovascular events, including stroke and myocardial infarction, result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. Current imaging modalities including magnetic resonance imaging (MRI aim to characterize anatomic and structural features of plaques rather than their content. Previously, we reported that macrophage-targeted delivery of gadolinium (Gd-based contrast agent (GBCA-HDL using high density lipoproteins (HDL-like particles significantly enhances the detection of plaques in an apolipoprotein (apo E knockout (KO mouse model, with an atherosclerotic wall/muscle normalized enhancement ratio (NER of 120% achieved. These particles are comprised of lipids and synthetic peptide fragments of the major protein of HDL, apo A-I, that contain a naturally occurring modification which targets the particles to macrophages. Targeted delivery minimizes the Gd dose and thus reduces the adverse effects of Gd. The aims of the current study were to test whether varying the GBCA-HDL particle shape and composition can further enhance atherosclerotic plaque MRI and control organ clearance of these agents. We show that the optimized GBCA-HDL particles are efficiently delivered intracellularly to and uptaken by both J774 macrophages in vitro and more importantly, by intraplaque macrophages in vivo, as evidenced by NER up to 160% and higher. This suggests high diagnostic power of our GBCA-HDL particles in the detection of vulnerable atherosclerotic plaques. Further, in contrast to discoidal, spherical GBCA-HDL exhibit hepatic clearance, which could further diminish adverse renal effects of Gd. Finally, activated macrophages are reliable indicators of any inflamed tissues and are implicated in other areas of unmet clinical need such as rheumatoid arthritis, sepsis and cancer, suggesting the

  1. An Interventional Magnetic Resonance Imaging Technique for the Molecular Characterization of Intraprostatic Dynamic Contrast Enhancement

    Directory of Open Access Journals (Sweden)

    Cynthia Ménard

    2005-01-01

    Full Text Available The biological characterization of an individual patient's tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in patients with prostate cancer.

  2. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  3. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.|info:eu-repo/dai/nl/338877169; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B|info:eu-repo/dai/nl/256054797; van Diest, Paul J.|info:eu-repo/dai/nl/075281775; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  4. Radiolabeled Adenoviral Sub-unit Proteins for Molecular Imaging and Therapeutic Applications in Oncology

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.; Meinken, G.; Springer, K. Awasthi, V.; Freimuth, P.

    2004-10-06

    The objective of this project was to develop and optimize new ligand systems, based on adenoviral vectors (intact adenovirus, adeno-viral fiber protein, and the knob protein), for delivering suitable radionuclides into tumor cells for molecular imaging and combined gene/radionuclide therapy of cancer.

  5. Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

    Czech Academy of Sciences Publication Activity Database

    Polášek, Miloslav; Yang, Y.; Schühle, D. T.; Yaseen, M. A.; Kim, Y. R.; Sung, Y. S.; Guimaraes, A. R.; Caravan, P.

    2017-01-01

    Roč. 7, Aug 14 (2017), č. článku 8114. ISSN 2045-2322 Institutional support: RVO:61388963 Keywords : fibrosis * molecular imaging * pancreatic cancer Subject RIV: FD - Oncology ; Hematology Impact factor: 4.259, year: 2016 https://www.nature.com/articles/s41598-017-08838-6

  6. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  7. Translation of New Molecular Imaging Approaches to the Clinical Setting : Bridging the Gap to Implementation

    NARCIS (Netherlands)

    van Es, Suzanne C; Venema, Clasina M; Glaudemans, Andor W J M; Lub-de Hooge, Marjolijn N; Elias, Sjoerd G; Boellaard, Ronald; Hospers, Geke A.P.; Schröder, Carolina P; de Vries, Elisabeth G E

    2016-01-01

    Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential

  8. Click-Chemistry-Mediated Rapid Microbubble Capture for Acute Thrombus Ultrasound Molecular Imaging.

    Science.gov (United States)

    Wang, Tuantuan; Yuan, Chuxiao; Dai, Bingyang; Liu, Yang; Li, Mingxi; Feng, Zhenqiang; Jiang, Qing; Xu, Zhihong; Zhao, Ningwei; Gu, Ning; Yang, Fang

    2017-07-18

    Bioorthogonal coupling chemistry has been studied as a potentially advantageous approach for molecular imaging because it offers rapid, efficient, and strong binding, which might also benefit stability, production, and chemical conjugation. The inverse-electron-demand Diels-Alder reaction between a 1,2,4,5-tetrazine and trans-cyclooctene (TCO) is an example of a highly selective and rapid bioorthogonal coupling reaction that has been used successfully to prepare targeted molecular imaging probes. Here we report a fast, reliable, and highly sensitive approach, based on a two-step pretargeting bioorthogonal approach, to achieving activated-platelet-specific CD62p-targeted thrombus ultrasound molecular imaging. Tetrazine-modified microbubbles (tetra-MBs) could be uniquely and rapidly captured by subsequent click chemistry of thrombus tagged with a trans-cyclooctene-pretreated CD62p antibody. Moreover, such tetra-MBs showed great long-term stability under physiological conditions, thus offering the ability to monitor thrombus changes in real time. We demonstrated for the first time that a bioorthogonal targeting molecular ultrasound imaging strategy based on tetra-MBs could be a simple but powerful tool for rapid diagnosis of acute thrombosis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. New possibilities for molecular imaging and intervention in breast cancer and other female malignancies

    NARCIS (Netherlands)

    Collarino, Angela

    2017-01-01

    The work described in this thesis shows new possibilities for molecular imaging in breast and vulvar cancer and demonstrates how to simultaneously encompass all current and future applications of nuclear medicine in female cancers. General introduction and outline of this thesis are reported in

  10. Biomolecular Imaging Mass Spectrometry : mapping molecular distributions in cells and tissue sections

    NARCIS (Netherlands)

    Altelaar, A.F.M.

    2007-01-01

    Imaging mass spectrometry (IMS) allows the investigation of both identity and localization of the molecular content directly from tissue sections, single cells and many other surfaces. To further develop the application of IMS, different approaches to IMS will be described in this thesis and the

  11. Target definition in salvage radiotherapy for recurrent prostate cancer: the role of advanced molecular imaging

    Directory of Open Access Journals (Sweden)

    Gaël eAmzalag

    2016-03-01

    Full Text Available Salvage radiotherapy (SRT represents the main treatment option for relapsing prostate cancer patients after radical prostatectomy (RP. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of the prostatic bed only or of the whole pelvis will depend on the localization of the recurrence, local or loco-regional. In the theragnostic imaging era, molecular imaging using Positron Emission Tomography (PET constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabelled choline PET imaging and multiparametric magnetic resonance imaging (MRI, associating the nodal and distant metastases identification based on PET and the local assessment by MRI. A new generation of targeted tracers, namely prostate specific membrane antigen (PSMA, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling using whole body SPECT-CT is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected.

  12. Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy

    Science.gov (United States)

    Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

    2017-01-01

    The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed. PMID:28117741

  13. Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy.

    Science.gov (United States)

    Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

    2017-01-22

    The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed.

  14. The complementary roles of dynamic contrast-enhanced MRI and {sup 18}F-fluorodeoxyglucose PET/CT for imaging of carotid atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Calcagno, Claudia; Ramachandran, Sarayu; Mani, Venkatesh; Millon, Antoine [Mount Sinai School of Medicine, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Izquierdo-Garcia, David [Harvard University - MIT - Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA (United States); Rosenbaum, David [Hopital Pitie Salpetriere, Paris (France); Tawakol, Ahmed [Harvard Medical School and Massachusetts General Hospital, Boston, MA (United States); Woodward, Mark [University of Sydney, George Institute, Sydney (Australia); Bucerius, Jan [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Rheinisch-Westfaelische Technische Hochschule Aachen, Department of Nuclear Medicine, Aachen (Germany); Moshier, Erin; Godbold, James [Mount Sinai School of Medicine, Biostatistics Shared Research Facility, New York, NY (United States); Kallend, David [F. Hoffmann-La Roche Ltd, Basel (Switzerland); Farkouh, Michael E. [Mount Sinai School of Medicine, Cardiovascular Institute, New York, NY (United States); Peter Munk Cardiac Centre and Li Ka Shing Knowledge Institute, Toronto (Canada); Fuster, Valentin [Mount Sinai School of Medicine, Cardiovascular Institute, New York, NY (United States); The Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid (Spain); Rudd, James H.F. [University of Cambridge, Division of Cardiovascular Medicine, Cambridge (United Kingdom); Fayad, Zahi A. [Mount Sinai School of Medicine, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Mount Sinai School of Medicine, Cardiovascular Institute, New York, NY (United States)

    2013-12-15

    Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and {sup 18}F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473). The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and {sup 18}F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and {sup 18}F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model. We found a significant inverse relationship between several perfusion indices by DCE-MRI and {sup 18}F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and {sup 18}F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or {sup 18}F-FDG PET metrics. In this study we observed a significant, weak inverse relationship between inflammation measured as {sup 18}F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different

  15. Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications.

    Science.gov (United States)

    Aime, Silvio; Castelli, Daniela Delli; Crich, Simonetta Geninatti; Gianolio, Eliana; Terreno, Enzo

    2009-07-21

    Contrast in magnetic resonance imaging (MRI) arises from changes in the intensity of the proton signal of water between voxels (essentially, the 3D counterpart of pixels). Differences in intervoxel intensity can be significantly enhanced with chemicals that alter the nuclear magnetic resonance (NMR) intensity of the imaged spins; this alteration can occur by various mechanisms. Paramagnetic lanthanide(III) complexes are used in two major classes of MRI contrast agent: the well-established class of Gd-based agents and the emerging class of chemical exchange saturation transfer (CEST) agents. A Gd-based complex increases water signal by enhancing the longitudinal relaxation rate of water protons, whereas CEST agents decrease water signal as a consequence of the transfer of saturated magnetization from the exchangeable protons of the agent. In this Account, we survey recent progress in both areas, focusing on how MRI is becoming a more competitive choice among the various molecular imaging methods. Compared with other imaging modalities, MRI is set apart by its superb anatomical resolution; however, its success in molecular imaging suffers because of its intrinsic insensitivity. A relatively high concentration of molecular agents (0.01-0.1 mM) is necessary to produce a local alteration in the water signal intensity. Unfortunately, the most desirable molecules for visualization in molecular imaging are present at much lower concentrations, in the nano- or picomolar range. Therefore, augmenting the sensitivity of MRI agents is key to the development of MR-based molecular imaging applications. In principle, this task can be tackled either by increasing the sensitivity of the reporting units, through the optimization of their structural and dynamic properties, or by setting up proper amplification strategies that allow the accumulation of a huge number of imaging reporters at the site of interest. For Gd-based agents, high sensitivities can be attained by exploiting a

  16. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  17. Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging

    Science.gov (United States)

    Yang, Chenying; Hou, Vivian W.; Girard, Emily J.; Nelson, Leonard Y.; Seibel, Eric J.

    2014-07-01

    Fluorescence molecular imaging with exogenous probes improves specificity for the detection of diseased tissues by targeting unambiguous molecular signatures. Additionally, increased diagnostic sensitivity is expected with the application of multiple molecular probes. We developed a real-time multispectral fluorescence-reflectance scanning fiber endoscope (SFE) for wide-field molecular imaging of fluorescent dye-labeled molecular probes at nanomolar detection levels. Concurrent multichannel imaging with the wide-field SFE also allows for real-time mitigation of the background autofluorescence (AF) signal, especially when fluorescein, a U.S. Food and Drug Administration approved dye, is used as the target fluorophore. Quantitative tissue AF was measured for the ex vivo porcine esophagus and murine brain tissues across the visible and near-infrared spectra. AF signals were then transferred to the unit of targeted fluorophore concentration to evaluate the SFE detection sensitivity for sodium fluorescein and cyanine. Next, we demonstrated a real-time AF mitigation algorithm on a tissue phantom, which featured molecular probe targeted cells of high-grade dysplasia on a substrate containing AF species. The target-to-background ratio was enhanced by more than one order of magnitude when applying the real-time AF mitigation algorithm. Furthermore, a quantitative estimate of the fluorescein photodegradation (photobleaching) rate was evaluated and shown to be insignificant under the illumination conditions of SFE. In summary, the multichannel laser-based flexible SFE has demonstrated the capability to provide sufficient detection sensitivity, image contrast, and quantitative target intensity information for detecting small precancerous lesions in vivo.

  18. Biomedical applications of functionalized hollow mesoporous silica nanoparticles: focusing on molecular imaging.

    Science.gov (United States)

    Shi, Sixiang; Chen, Feng; Cai, Weibo

    2013-12-01

    Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle, have recently gained increasing interest owing to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in the engineering of functionalized HMSNs (i.e., f-HMSNs), with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, PET, MRI and ultrasound imaging in preclinical studies. Finally, we discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy.

  19. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guanglei, E-mail: guangleizhang@bjtu.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044 (China); Pu, Huangsheng; Liu, Fei; Bai, Jing [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); He, Wei [China Institute of Sport Science, Beijing 100061 (China); Luo, Jianwen, E-mail: luo-jianwen@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Center for Biomedical Imaging Research, School of Medicine, Tsinghua University, Beijing 100084 (China)

    2015-02-23

    Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but also make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.

  20. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Yan, Susu [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Roper, Justin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2014-01-15

    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  1. Preventing and arresting coronary atherosclerosis.

    Science.gov (United States)

    Roberts, W C

    1995-09-01

    The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.

  2. Inflammation and coagulation in atherosclerosis.

    Science.gov (United States)

    Krychtiuk, K A; Kastl, S P; Speidl, W S; Wojta, J

    2013-01-01

    Cardiovascular diseases remain to be the leading cause of death in Western societies. Despite major findings in vascular biology that lead to a better understanding of the pathomechanisms involved in atherosclerosis, treatment of the disease has only changed slightly within the last years. A big body of evidence suggests that atherosclerosis is a chronic inflammatory disease of the vessel wall. Accumulation and peroxidation of LDL-particles within the vessel wall trigger a strong inflammatory response, causing macrophage and T-cell accumulation within the vessel wall. Additionally, B-cells and specific antibodies against LDL-particles, as well as the complement system are implicated in atherogenesis. Besides data from clinical trials and autopsy studies it was the implementation of mouse models of atherosclerosis and the emerging field of direct gen-modification that lead to a thorough description of the pathophysiological mechanisms involved in the disease and created overwhelming evidence for a participation of the immune system. Recently, the cross-talk between coagulation and inflammation in atherogenesis has gained attention. Serious limitations and disparities in the pathophysiology of atherosclerosis in mice and men complicated the translation of experimental data into clinical practice. Despite these limitations, new anti-inflammatory medical therapies in cardiovascular disease are currently being tested in clinical trials.

  3. Trained innate immunity and atherosclerosis

    NARCIS (Netherlands)

    Bekkering, S.; Joosten, L.A.B.; Meer, J.W.M. van der; Netea, M.G.; Riksen, N.P.

    2013-01-01

    PURPOSE OF REVIEW: Monocytes/macrophages play a decisive role in the development and progression of atherosclerosis. It is currently unknown what stimuli initiate and orchestrate the activation of these cells in atherogenesis. In this review, we postulate that the novel concept of 'trained immunity'

  4. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study.

    Science.gov (United States)

    Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio; Ibañez, Borja; López-Melgar, Beatriz; Laclaustra, Martín; Oliva, Belén; Mocoroa, Agustín; Mendiguren, José; Martínez de Vega, Vicente; García, Laura; Molina, Jesús; Sánchez-González, Javier; Guzmán, Gabriela; Alonso-Farto, Juan C; Guallar, Eliseo; Civeira, Fernando; Sillesen, Henrik; Pocock, Stuart; Ordovás, José M; Sanz, Ginés; Jiménez-Borreguero, Luis Jesús; Fuster, Valentín

    2015-06-16

    Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2-3 sites), or generalized (4-6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318. © 2015 American Heart Association, Inc.

  5. Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

  6. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    DEFF Research Database (Denmark)

    2016-01-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B...... that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production...... of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis....

  7. Disease-Specific Target Gene Expression Profiling of Molecular Imaging Probes: Database Development and Clinical Validation

    Directory of Open Access Journals (Sweden)

    Lawrence Wing-Chi Chan

    2014-08-01

    Full Text Available Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2- deoxy-2-D-glucose (FDG, respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/.

  8. Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green

    Science.gov (United States)

    Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

    2016-01-01

    Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID:26864116

  9. A two-step stimulus-response cell-SELEX method to generate a DNA aptamer to recognize inflamed human aortic endothelial cells as a potential in vivo molecular probe for atherosclerosis plaque detection.

    Science.gov (United States)

    Ji, Kaili; Lim, Wee Siang; Li, Sam Fong Yau; Bhakoo, Kishore

    2013-08-01

    Aptamers are single-stranded oligonucleotides that are capable of binding wide classes of targets with high affinity and specificity. Their unique three-dimensional structures present numerous possibilities for recognizing virtually any class of target molecules, making them a promising alternative to antibodies used as molecular probes in biomedical analysis and clinical diagnosis. In recent years, cell-systematic evolution of ligands by exponential enrichment (SELEX) has been used extensively to select aptamers for various cell targets. However, aptamers that have evolved from cell-SELEX to distinguish the "stimulus-response cell" have not previously been reported. Moreover, a number of cumbersome and time-consuming steps involved in conventional cell-SELEX reduce the efficiency and efficacy of the aptamer selection. Here, we report a "two-step" methodology of cell-SELEX that successfully selected DNA aptamers specifically against "inflamed" endothelial cells. This has been termed as stimulus-response cell-SELEX (SRC-SELEX). The SRC-SELEX enables the selection of aptamers to distinguish the cells activated by stimulus of healthy cells or cells isolated from diseased tissue. We report a promising aptamer, N55, selected by SRC-SELEX, which can bind specifically to inflamed endothelial cells both in cell culture and atherosclerotic plaque tissue. This aptamer probe was demonstrated as a potential molecular probe for magnetic resonance imaging to target inflamed endothelial cells and atherosclerotic plaque detection.

  10. Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications.

    Science.gov (United States)

    Tapia-Vieyra, Juana Virginia; Delgado-Coello, Blanca; Mas-Oliva, Jaime

    2017-01-01

    Atherosclerosis and cancer are chronic diseases considered two of the main causes of death all over the world. Taking into account that both diseases are multifactorial, they share not only several important molecular pathways but also many ethiological and mechanistical processes from the very early stages of development up to the advanced forms in both pathologies. Factors involved in their progression comprise genetic alterations, inflammatory processes, uncontrolled cell proliferation and oxidative stress, as the most important ones. The fact that external effectors such as an infective process or a chemical insult have been proposed to initiate the transformation of cells in the artery wall and the process of atherogenesis, emphasizes many similarities with the progression of the neoplastic process in cancer. Deregulation of cell proliferation and therefore cell cycle progression, changes in the synthesis of important transcription factors as well as adhesion molecules, an alteration in the control of angiogenesis and the molecular similarities that follow chronic inflammation, are just a few of the processes that become part of the phenomena that closely correlates atherosclerosis and cancer. The aim of the present study is therefore, to provide new evidence as well as to discuss new approaches that might promote the identification of closer molecular ties between these two pathologies that would permit the recognition of atherosclerosis as a pathological process with a very close resemblance to the way a neoplastic process develops, that might eventually lead to novel ways of treatment. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  11. Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging

    Science.gov (United States)

    Gao, Liang; Hammoudi, Ahmad A.; Li, Fuhai; Thrall, Michael J.; Cagle, Philip T.; Chen, Yuanxin; Yang, Jian; Xia, Xiaofeng; Fan, Yubo; Massoud, Yehia; Wang, Zhiyong; Wong, Stephen T. C.

    2012-06-01

    The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.

  12. Molecular imaging of tumor invasion and metastases: the role of MRI†

    Science.gov (United States)

    McCann, Thomas E.; Kosaka, Nobuyuki; Turkbey, Baris; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka

    2012-01-01

    The processes of tumor invasion and metastasis have been well characterized at the molecular level, and numerous biomarkers of tumor aggressiveness have been discovered. Molecular imaging offers the opportunity to depict specific cell markers relevant to tumor aggressiveness. Here, we describe the role of MRI in identifying tumor invasiveness and metastasis with reference to other methods. Target-specific molecular imaging probes for tumor invasiveness have been developed for positron emission tomography and optical imaging, but progress in MRI has been slower. For example, proteases associated with tumor invasion, such as specific matrix metalloproteinases or cathepsins, can be targeted in vivo using optical and positron emission tomography methods, but have not yet been successful with MRI. In addition, we describe the use of MRI to detect metastases. Novel MR contrast agents based on iron oxide and dendrimer nanomaterials allow for better characterization of tumor metastases. Organ-specific MR contrast agents are used to identify metastatic disease in the liver. Finally, diffusion-weighted whole-body MRI is discussed as an alternative offered by MRI that does not require the use of molecular probes to screen distant metastases. PMID:21793070

  13. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn

    2016-01-01

    Full Text Available Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

  14. Bioengineered probes for molecular magnetic resonance imaging in the nervous system.

    Science.gov (United States)

    Hsieh, Vivian; Jasanoff, Alan

    2012-08-15

    The development of molecular imaging probes has changed the nature of neurobiological research. Some of the most notable successes have involved the use of biological engineering techniques for the creation of fluorescent protein derivatives for optical imaging, but recent work has also led to a number of bioengineered probes for magnetic resonance imaging (MRI), the preeminent technique for noninvasive investigation of brain structure and function. Molecular MRI agents are beginning to be applied for experiments in the nervous system, where they have the potential to bridge from molecular to systems or organismic levels of analysis. Compared with canonical synthetic small molecule agents, biomolecular or semibiosynthetic MRI contrast agents offer special advantages due to their amenability to molecular engineering approaches, their properties in some cases as catalysts, and their specificity in targeting and ligand binding. Here, we discuss an expanding list of instances where biological engineering techniques have aided in the design of MRI contrast agents and reporter systems, examining both advantages and limitations of these types of probes for studies in the central nervous system.

  15. Technological advances in Preclinical Molecular Imaging; Avances tecnológicos en Imagen Molecular Preclínica

    Energy Technology Data Exchange (ETDEWEB)

    Peña-Zalbidea, S.; Vaquero, J.

    2014-07-01

    Molecular imaging is undergoing an intense activity, mainly due to the availability of new detection and image reconstruction technologies, which in recent years have improved significantly both the resolution and sensitivity of these methods. The greatest potential for innovation comes from multimodality imaging, which combines information from more than one imaging technique and exploits the synergies between them. The main arguments in favour of these devices are the possibility of performing intrinsically registered scans in a minimum time and without moving the animal. Currently, the combination of PET and MRI as a hybrid imaging modality is receiving great attention and although its potential is clear, as it was with the PET/CT, this technology will have to overcome certain limitations and demonstrate its value for different applications. [Spanish] La imagen molecular es un área de investigación muy activa acelerada en los últimos años por la disponibilidad de nuevas tecnologías de detección y reconstrucción de imágenes. Estas innovaciones han permitido mejorar considerablemente tanto la resolución como la sensibilidad de las imágenes obtenidas sobre modelos preclínicos desarrollados en pequeños animales (ratón y rata principalmente). El mayor potencial de esta tecnología proviene de la imagen multimodalidad, que combina información de más de una técnica de imagen y explota las posibles sinergias entre ellas al integrar en una sola imagen “forma y función”. Los principales argumentos a favor de estos dispositivos multimodales son la posibilidad de hacer las exploraciones intrínsecamente registradas en un tiempo reducido, y sin necesidad de mover el animal entre diferentes equipos. De todas las posibles combinaciones la que está reclamando más la atención últimamente es la PET/IRM (tomografía por emisión de positrones e imagen de resonancia magnética), aunque de momento la PET/CT (tomografía por emisión de positrones y tomograf

  16. Development of new Molecular Imaging probes; Desarrollo de nuevas sondas de Imagen Molecular

    Energy Technology Data Exchange (ETDEWEB)

    Gómez-Vallejo, V.; Baz, Z.; Llop, J.

    2014-07-01

    Nuclear Imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) are essential tools for the early diagnose of certain pathologies, and have been widely applied to the mechanistic investigation of disease, the visualization of biological and physiological phenomena and in the process of drug development. PET and SPECT require the administration of a radiotracer (compound labelled with a radioactive nuclide) to the subject under investigation (patient, healthy volunteer or experimental animal). Due to their high sensitivity and their noninvasive nature, nuclear imaging techniques have a great potential. However, only a few radiotracers are currently routinely used in clinical diagnose. In contrast, new tracers suitable for the visualization of new targets or showing improved specificity, selectivity or pharmacokinetic properties are continuously designed, synthesized and assayed in the preclinical setting. Far from performing an exhaustive revision of the new radiotracers currently under development, this paper aims to collate recent advances related to the preparation of novel nuclear imaging probes, which have a significant scientific impact in terms of literature volume, and which could be translated to the clinical environment in the near future. First, peptides and nanoparticles (NPs) are discussed. Finally, antibody derivatives and the recently developed pretargeting strategy, which enables the visualization of tumours while lowering significantly the effective dose posed on the subject under investigation, will be briefly covered. [Spanish] Las técnicas de imagen nuclear, entre las que se encuentran la tomografía por emisión de positrones (PET) y la tomografía por emisión de fotón único (SPECT) son herramientas fundamentales no sólo en el entorno clínico diagnóstico, sino también para el estudio mecanístico de determinadas patologías, la visualización de procesos biol

  17. MDM2 Molecular Imaging for the Prediction of Chemotherapeutic Sensitivity in Human Breast Cancer Xenograft

    Directory of Open Access Journals (Sweden)

    Peng Fu

    2014-08-01

    Full Text Available The aim of the present study was to investigate the possible use of mouse double-minute 2 (MDM2 molecular imaging to predict chemotherapeutic sensitivity in breast cancer xenografts (BCXs. MCF-7 cells were transfected with MDM2 antisense oligonucleotides (ASONs, and MDM2 expression levels were determined by Western blotting. Cell viability was assessed by 3-(4,5- dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay in MCF-7 cells transfected with ASONs and treated with paclitaxel. BCXs were established in nude mice by injection of ASONs, and tumor volumes were measured after paclitaxel treatment. MDM2 ASONs were labeled with 99mTc to generate an MDM2 molecular probe, and MDM2 expression levels were evaluated by imaging and Western blotting. MDM2 ASONs downregulated MDM2 expression in a dose-dependent manner and increased the rate of paclitaxel-induced cell growth inhibition. Imaging of tumors revealed significant differences in the tumor to skeletal muscle (T/M ratio between groups. Tumor MDM2 protein expression was correlated with T/M ratios at 4 hours (R = .880 and 10 hours (R = .886. The effect of paclitaxel varied among nude mice bearing BCXs with different concentrations of ASONs, as shown by differences in tumor growth. MDM2 molecular imaging could be a promising method for predicting the sensitivity of BCXs to chemotherapy.

  18. Molecular imaging of vascular endothelial growth factor receptors in graft arteriosclerosis.

    Science.gov (United States)

    Zhang, Jiasheng; Razavian, Mahmoud; Tavakoli, Sina; Nie, Lei; Tellides, George; Backer, Joseph M; Backer, Marina V; Bender, Jeffrey R; Sadeghi, Mehran M

    2012-08-01

    Vascular endothelial growth factor (VEGF) signaling plays a key role in the pathogenesis of vascular remodeling, including graft arteriosclerosis. Graft arteriosclerosis is the major cause of late organ failure in cardiac transplantation. We used molecular near-infrared fluorescent imaging with an engineered Cy5.5-labeled single-chain VEGF tracer (scVEGF/Cy) to detect VEGF receptors and vascular remodeling in human coronary artery grafts by molecular imaging. VEGF receptor specificity of probe uptake was shown by flow cytometry in endothelial cells. In severe combined immunodeficiency mice, transplantation of human coronary artery segments into the aorta followed by adoptive transfer of allogeneic human peripheral blood mononuclear cells led to significant neointima formation in the grafts over a period of 4 weeks. Near-infrared fluorescent imaging of transplant recipients at 4 weeks demonstrated focal uptake of scVEGF/Cy in remodeling artery grafts. Uptake specificity was demonstrated using an inactive homolog of scVEGF/Cy. scVEGF/Cy uptake predominantly localized in the neointima of remodeling coronary arteries and correlated with VEGF receptor-1 but not VEGF receptor-2 expression. There was a significant correlation between scVEGF/Cy uptake and transplanted artery neointima area. Molecular imaging of VEGF receptors may provide a noninvasive tool for detection of graft arteriosclerosis in solid organ transplantation.

  19. Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy.

    Science.gov (United States)

    Hippe, Daniel S; Phan, Binh An P; Sun, Jie; Isquith, Daniel A; O'Brien, Kevin; Crouse, John R; Anderson, Todd; Huston, John; Marcovina, Santica M; Hatsukami, Thomas S; Yuan, Chun; Zhao, Xue-Qiao

    2018-01-04

    To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression. P values were adjusted for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P=0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (β=0.34 per 1-SD increase of Lp(a); 95% CI, 0.15-0.52; P<0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (β=0.33; 95% CI, 0.15-0.52; P<0.001). Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden. © 2018 American Heart Association, Inc.

  20. Ultrasound molecular imaging of secreted frizzled related protein-2 expression in murine angiosarcoma.

    Directory of Open Access Journals (Sweden)

    James K Tsuruta

    Full Text Available Angiosarcoma is a biologically aggressive vascular malignancy with a high metastatic potential. In the era of targeted medicine, knowledge of specific molecular tumor characteristics has become more important. Molecular imaging using targeted ultrasound contrast agents can monitor tumor progression non-invasively. Secreted frizzled related protein 2 (SFRP2 is a tumor endothelial marker expressed in angiosarcoma. We hypothesize that SFRP2-directed imaging could be a novel approach to imaging the tumor vasculature. To develop an SFRP2 contrast agent, SFRP2 polyclonal antibody was biotinylated and incubated with streptavidin-coated microbubbles. SVR angiosarcoma cells were injected into nude mice, and when tumors were established the mice were injected intravenously with the SFRP2 -targeted contrast agent, or a control streptavidin-coated contrast agent. SFRP2 -targeted contrast agent detected tumor vasculature with significantly more signal intensity than control contrast agent: the normalized fold-change was 1.6 ± 0.27 (n = 13, p = 0.0032. The kidney was largely devoid of echogenicity with no significant difference between the control contrast agent and the SFRP2-targeted contrast agent demonstrating that the SFRP2-targeted contrast agent was specific to tumor vessels. Plotting average pixel intensity obtained from SFRP2-targeted contrast agent against tumor volume showed that the average pixel intensity increased as tumor volume increased. In conclusion, molecularly-targeted imaging of SFRP2 visualizes angiosarcoma vessels, but not normal vessels, and intensity increases with tumor size. Molecular imaging of SFRP2 expression may provide a rapid, non-invasive method to monitor tumor regression during therapy for angiosarcoma and other SFRP2 expressing cancers, and contribute to our understanding of the biology of SFRP2 during tumor development and progression.

  1. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort

    DEFF Research Database (Denmark)

    Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio

    2015-01-01

    BACKGROUND: Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. METHODS AND RESULTS: The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mea......-risk individuals, suggesting added value of imaging for diagnosis and prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318....

  2. Imaging mass spectrometry: Molecular microscopy for the new age of biology and medicine.

    Science.gov (United States)

    Caprioli, Richard M

    2016-06-01

    Imaging mass spectrometry provides a powerful tool for monitoring and discovery of molecular processes in the spatial domain in tissues for research and practical applications in both biology and medicine. This technology directly measures molecular compounds in tissues without the use of target-specific reagents such as antibodies, is applicable to a wide variety of analytes, and can provide spatial resolutions below the single cell level. Importantly, it has paradigm shifting capabilities in clinical applications, especially for anatomic pathology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Imaging modes of atomic force microscopy for application in molecular and cell biology

    Science.gov (United States)

    Dufrêne, Yves F.; Ando, Toshio; Garcia, Ricardo; Alsteens, David; Martinez-Martin, David; Engel, Andreas; Gerber, Christoph; Müller, Daniel J.

    2017-04-01

    Atomic force microscopy (AFM) is a powerful, multifunctional imaging platform that allows biological samples, from single molecules to living cells, to be visualized and manipulated. Soon after the instrument was invented, it was recognized that in order to maximize the opportunities of AFM imaging in biology, various technological developments would be required to address certain limitations of the method. This has led to the creation of a range of new imaging modes, which continue to push the capabilities of the technique today. Here, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.

  4. Imaging modes of atomic force microscopy for application in molecular and cell biology.

    Science.gov (United States)

    Dufrêne, Yves F; Ando, Toshio; Garcia, Ricardo; Alsteens, David; Martinez-Martin, David; Engel, Andreas; Gerber, Christoph; Müller, Daniel J

    2017-04-06

    Atomic force microscopy (AFM) is a powerful, multifunctional imaging platform that allows biological samples, from single molecules to living cells, to be visualized and manipulated. Soon after the instrument was invented, it was recognized that in order to maximize the opportunities of AFM imaging in biology, various technological developments would be required to address certain limitations of the method. This has led to the creation of a range of new imaging modes, which continue to push the capabilities of the technique today. Here, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.

  5. Justifying molecular images in cell biology textbooks: From constructions to primary data.

    Science.gov (United States)

    Serpente, Norberto

    2016-02-01

    For scientific claims to be reliable and productive they have to be justified. However, on the one hand little is known on what justification precisely means to scientists, and on the other the position held by philosophers of science on what it entails is rather limited; for justifications customarily refer to the written form (textual expressions) of scientific claims, leaving aside images, which, as many cases from the history of science show are relevant to this process. The fact that images can visually express scientific claims independently from text, plus their vast variety and origins, requires an assessment of the way they are currently justified and in turn used as sources to justify scientific claims in the case of particular scientific fields. Similarly, in view of the different nature of images, analysis is required to determine on what side of the philosophical distinction between data and phenomena these different kinds of images fall. This paper historicizes and documents a particular aspect of contemporary life sciences research: the use of the molecular image as vehicle of knowledge production in cell studies, a field that has undergone a significant shift in visual expressions from the early 1980s onwards. Focussing on textbooks as sources that have been overlooked in the historiography of contemporary biomedicine, the aim is to explore (1) whether the shift of cell studies, entailing a superseding of the optical image traditionally conceptualised as primary data, by the molecular image, corresponds with a shift of justificatory practices, and (2) to assess the role of the molecular image as primary data. This paper also explores the dual role of images as teaching resources and as resources for the construction of knowledge in cell studies especially in its relation to discovery and justification. Finally, this paper seeks to stimulate reflection on what kind of archival resources could benefit the work of present and future epistemic

  6. Optical Molecular Imaging of Epidermal Growth Factor Receptor Expression to Improve Detection of Oral Neoplasia

    Directory of Open Access Journals (Sweden)

    Nitin Nitin

    2009-06-01

    Full Text Available Background: The development of noninvasive molecular imaging approaches has the potential to improve management of cancer. Methods: In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647 conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined. Results: The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 µm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging. Conclusions: Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.

  7. Enhanced imaging resolution in dynamic fluorescence molecular tomography by multispectral excitation method (Conference Presentation)

    Science.gov (United States)

    Chen, Maomao; Zhou, Yuan; Su, Han; Zhang, Dong; Luo, Jianwen

    2017-03-01

    Dynamic fluorescence molecular tomography (DFMT) is a promising method for the quantitative evaluation of the metabolic process of fluorescent agents in body. However, the resolution is limited due to the ill-posed nature of fluorescence molecular tomography (FMT) and the high absorption and scattering of the fluorescent light in biological tissues. In this paper, the resolution of DFMT is improved by multispectral excitation method. Firstly, the imaged object with varied fluorescent concentrations at different time points is excited by several excitation lights with different wavelengths, and the fluorescent images are collected. Secondly, the individual FMT images at different time points are respectively reconstructed, and independent component analysis (ICA) is employed to decompose the fluorescent targets. The independent components (ICs) and corresponding spectrum courses (SCs) which obtained from ICA represent the spatial structures and spectral variations of the fluorescent targets, respectively. Thirdly, the ICs and SCs are combined to quantitatively recover the concentrations of individual fluorescent targets. Finally, the metabolic parameters and DFMT images are obtained by fitting the FMT images of each fluorescent targets at different time points into a two compartment model. Numerical simulations are carried out to validate the feasibility of the proposed method. The results demonstrate that the resolution of DFMT is significantly improved. The metabolic curves can be correctly recovered even when the edge-edge-distance of the fluorescent targets is less than 0.1 cm.

  8. A tale of two photons: radioluminescence and its application in molecular imaging

    Science.gov (United States)

    Pratx, Guillem

    2017-02-01

    Optical and ionizing radiation are two physical ways in which we can probe the living world. Until recently, these forms of radiation were used in distinct imaging and therapeutic applications—radiation therapy, photodynamic therapy, X-ray imaging, and diffuse optical tomography, to name a few. It has now been recognized that physical phenomena in which ionizing radiation and light are inherently coupled may provide powerful new capabilities for imaging and treating diseases. This presentation will review the physics and applications of radioluminescence, with a particular focus on molecular imaging. One such method, X-ray luminescence computed tomography (XLCT), uses narrow kilovolt X-ray beams to stimulate optical emissions from biologically targeted radioluminescent nanoparticles, thus providing high-resolution images even deep in tissue. A different phenomenon, Cherenkov luminescence, can also be harnessed to localize radiopharmaceuticals in vivo, allowing surgeons to visualize the molecular status of the tissues they are resecting. Recent progress towards routine implantation of these methods will be reviewed and sources of endogenous radioluminescence signal will be discussed.

  9. Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Benjamin L. Franc

    2003-10-01

    Full Text Available The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.

  10. Mapping Molecular Function to Biological Nanostructure: Combining Structured Illumination Microscopy with Fluorescence Lifetime Imaging (SIM + FLIM

    Directory of Open Access Journals (Sweden)

    Frederik Görlitz

    2017-07-01

    Full Text Available We present a new microscope integrating super-resolved imaging using structured illumination microscopy (SIM with wide-field optically sectioned fluorescence lifetime imaging (FLIM to provide optical mapping of molecular function and its correlation with biological nanostructure below the conventional diffraction limit. We illustrate this SIM + FLIM capability to map FRET readouts applied to the aggregation of discoidin domain receptor 1 (DDR1 in Cos 7 cells following ligand stimulation and to the compaction of DNA during the cell cycle.

  11. Single-molecule femtochemistry: molecular imaging at the space-time limit.

    Science.gov (United States)

    Petek, Hrvoje

    2014-01-28

    Through a combination of light and electron probes, it may be possible to record single-molecule dynamics with simultaneous sub-Ångstrom spatial and femtosecond temporal resolution. Single-molecule femtochemistry is becoming a realistic prospect through a melding of laser spectroscopy and electron microscopy techniques. The paper by Lee et al. in this issue of ACS Nano takes a significant step toward chemical imaging at the space-time limit of chemical processes. By imaging electroluminescence spectra of single porphyrin molecules with submolecular resolution, the authors extract the implicit femtosecond dynamics of the coupled electron orbital-molecular skeletal motion triggered by a reduction-oxidation scattering process.

  12. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  13. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.

    Science.gov (United States)

    Hoseini, Zahra; Sepahvand, Fatemeh; Rashidi, Bahman; Sahebkar, Amirhossein; Masoudifar, Aria; Mirzaei, Hamed

    2018-03-01

    Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1β and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1β, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK-1 and ASK-1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK-induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained. © 2017 Wiley Periodicals, Inc.

  14. From protein-protein interaction to therapy response: Molecular imaging of heat shock proteins

    Energy Technology Data Exchange (ETDEWEB)

    Niu Gang [Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484 (United States); Chen Xiaoyuan [Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484 (United States)], E-mail: shawchen@stanford.edu

    2009-05-15

    HSP70 promoter-driven gene therapy and inhibition of HSP90 activity with small molecule inhibitors are two shining points in a newly developed cohort of cancer treatment. For HSP70 promoters, high efficiency and heat inducibility within a localized region make it very attractive to clinical translation. The HSP90 inhibitors exhibit a broad spectrum of anticancer activities due to the downstream effects of HSP90 inhibition, which interfere with a wide range of signaling processes that are crucial for the malignant properties of cancer cells. In this review article, we summarize exciting applications of newly emerged molecular imaging techniques as they relate to HSP, including protein-protein interactions of HSP90 complexes, therapeutic response of tumors to HSP90 inhibitors, and HSP70 promoters-controlled gene therapy. In the HSPs context, molecular imaging is expected to play a vital role in promoting drug development and advancing individualized medicine.

  15. Image-charge-induced localization of molecular orbitals at metal-molecule interfaces

    DEFF Research Database (Denmark)

    Strange, M.; Thygesen, K. S.

    2012-01-01

    -conjugated molecular wire in contact with a metal surface. We find that image charge effects pull the frontier molecular orbitals toward the metal surface, while orbitals with higher or lower energy are pushed away. This affects both the size of the energetic image charge shifts and the coupling of the individual......Quasiparticle (QP) wave functions, also known as Dyson orbitals, extend the concept of single-particle states to interacting electron systems. Here we employ many-body perturbation theory in the GW approximation to calculate the QP wave functions for a semiempirical model describing a pi...... orbitals to the metal substrate. Full diagonalization of the QP equation and, to some extent, self-consistency in the GW self-energy, is important to describe the effect, which is not captured by standard density functional theory or Hartree-Fock. These results should be important for the understanding...

  16. The Changing Face of Vascular Interventional Radiology: The Future Role of Pharmacotherapies and Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tapping, Charles R., E-mail: crtapping@doctors.org.uk; Bratby, Mark J., E-mail: mark.bratby@ouh.nhs.uk [Oxford University Hospitals, John Radcliffe Hospital, Department of Radiology (United Kingdom)

    2013-08-01

    Interventional radiology has had to evolve constantly because there is the ever-present competition and threat from other specialties within medicine, surgery, and research. The development of new technologies, techniques, and therapies is vital to broaden the horizon of interventional radiology and to ensure its continued success in the future. In part, this change will be due to improved chronic disease prevention altering what we treat and in whom. The most important of these strategies are the therapeutic use of statins, Beta-blockers, angiotensin-converting enzyme inhibitors, and substances that interfere with mast cell degeneration. Molecular imaging and therapeutic strategies will move away from conventional techniques and nano and microparticle molecular technology, tissue factor imaging, gene therapy, endothelial progenitor cells, and photodynamic therapy will become an important part of interventional radiology of the future. This review looks at these new and exciting technologies.

  17. Metal-Organic Framework-Based Nanomedicine Platforms for Drug Delivery and Molecular Imaging.

    Science.gov (United States)

    Cai, Wen; Chu, Cheng-Chao; Liu, Gang; Wáng, Yì-Xiáng J

    2015-10-07

    Metal-organic frameworks (MOFs), which are a unique class of hybrid porous materials built from metal ions and organic linkers, have attracted significant research interest in recent years. Compared with conventional porous materials, MOFs exhibit a variety of advantages, including a large surface area, a tunable pore size and shape, an adjustable composition and structure, biodegradability, and versatile functionalities, which enable MOFs to perform as promising platforms for drug delivery, molecular imaging, and theranostic applications. In this article, the recent research progress related to nanoscale metal-organic frameworks (NMOFs) is summarized with a focus on synthesis strategies and drug delivery, molecular imaging, and theranostic applications. The future challenges and opportunities of NMOFs are also discussed in the context of translational medical research. More effort is warranted to develop clinically translatable NMOFs for various applications in nanomedicine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Carotid versus coronary atherosclerosis burdens in acute compared with chronic symptomatic coronary artery disease.

    Science.gov (United States)

    LeBlanc, Stéphanie; Bibeau, Karine; Bertrand, Olivier F; Lévesque, Valérie; Deschênes St-Pierre, Béatrice; Pibarot, Philippe; Després, Jean-Pierre; Larose, Eric

    2017-08-01

    Prediction of coronary events remains elusive. Carotid atherosclerosis may be a surrogate for coronary risk, as carotid and coronary diseases occur simultaneously - albeit at times with a weak association - depending on clinical presentation. We investigated carotid and coronary atherosclerosis in men with new-onset unstable coronary artery disease (CAD) presenting with acute ST-segment elevation myocardial infarction (STEMI) vs. long-standing severe chronic stable angina (CSA). Bilateral carotid artery and 3-vessel coronary artery atherosclerosis burdens were measured within 1 month, respectively, by 3D-volumetric carotid magnetic resonance imaging and coronary angiography-derived modified CASS-50 score. Men with STEMI (n = 50) and long-standing CSA (n = 50), matched for age, were enrolled (58.6 ± 8.8 years). All of them had carotid atherosclerosis. Atherosclerosis burden was greater in the carotid arteries of STEMI vs. CSA (wall volume: 196.2 ± 44.4 vs. 169.2 ± 38.0 mm3/4 mm, p = 0.002), but greater in the coronary arteries of CSA vs. STEMI (modified CASS-50 score: 3 vs. 1, p < 0.0001). Normalized wall index (NWI) of internal carotid was associated with modified CASS-50 score in STEMI (ρ = 0.40, p = 0.022) and in CSA (ρ = -0.39, p = 0.031). Carotid atherosclerosis was observed in all CAD patients, and atherosclerosis burden in carotid and in coronary arteries varied according to clinical presentation.

  19. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  20. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine

    Science.gov (United States)

    Pool, Martin; de Boer, H. Rudolf; Hooge, Marjolijn N. Lub-de; van Vugt, Marcel A.T.M.; de Vries, Elisabeth G.E.

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance. PMID:28638489

  1. Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue.

    Science.gov (United States)

    Davis, Scott C; Pogue, Brian W; Springett, Roger; Leussler, Christoph; Mazurkewitz, Peter; Tuttle, Stephen B; Gibbs-Strauss, Summer L; Jiang, Shudong S; Dehghani, Hamid; Paulsen, Keith D

    2008-06-01

    A multichannel spectrally resolved optical tomography system to image molecular targets in small animals from within a clinical MRI is described. Long source/detector fibers operate in contact mode and couple light from the tissue surface in the magnet bore to 16 spectrometers, each containing two optical gratings optimized for the near infrared wavelength range. High sensitivity, cooled charge coupled devices connected to each spectrograph provide detection of the spectrally resolved signal, with exposure times that are automated for acquisition at each fiber. The design allows spectral fitting of the remission light, thereby separating the fluorescence signal from the nonspecific background, which improves the accuracy and sensitivity when imaging low fluorophore concentrations. Images of fluorescence yield are recovered using a nonlinear reconstruction approach based on the diffusion approximation of photon propagation in tissue. The tissue morphology derived from the MR images serves as an imaging template to guide the optical reconstruction algorithm. Sensitivity studies show that recovered values of indocyanine green fluorescence yield are linear to concentrations of 1 nM in a 70 mm diameter homogeneous phantom, and detection is feasible to near 10 pM. Phantom data also demonstrate imaging capabilities of imperfect fluorophore uptake in tissue volumes of clinically relevant sizes. A unique rodent MR coil provides optical fiber access for simultaneous optical and MR data acquisition of small animals. A pilot murine study using an orthotopic glioma tumor model demonstrates optical-MRI imaging of an epidermal growth factor receptor targeted fluorescent probe in vivo.

  2. Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy

    OpenAIRE

    Mi Li; Dan Dang; Lianqing Liu; Ning Xi; Yuechao Wang

    2017-01-01

    The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used ...

  3. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Johan L M Björkegren

    2014-02-01

    Full Text Available Plasma cholesterol lowering (PCL slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80% and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-Apob (100/100 Mttp (flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions.

  4. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    OpenAIRE

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role o...

  5. DONOR-TRANSMITTED CORONARY ATHEROSCLEROSIS

    Directory of Open Access Journals (Sweden)

    B. L. Mironkov

    2014-01-01

    Full Text Available Aim. To estimate opportunities, prospects and safety of using heart transplants from aged donors who are at high risk of coronary atherosclerosis.Materials and methods. Over the period from March 1987 to May 2014450 heart transplantations (HTx were performed in V.I.Shumakov Federal Research Center of Transplantology and Artifi cial Organs. During the fi rst month after HTx coronarography was made to 152 (37,8% recipients inorder to exclude/confi rm donor-transmitted coronary atherosclerosis (DTCA and to identify tactics of treatment. Coronary atherosclerosis was detected among 16 patients (3,6% of total number of HTx, 15 (93,8% men and 1 (6,2% women. Mean age of recipients with DTCA at the moment of HTx was 48,3 ± 13,1 years.Results. Hemodynamically relevant coronary atherosclerosis was not detected and percutaneous coronary intervention (PCI was not made in the group of patients with the mean age of 42,24 ± 8,91 years. Using heart transplants from aged donors is connected with increasing risk of DTCA among the recipients. DTCA-dependent PCI is not connected with coronary mortality. Actuarial survival rate of patients who underwent PCI is comparable with the same one in the total population of HTx recipients and is equal to 87,5% at 5 years and less.Conclusion. Hearts from aged donors (older than 50 years may be used for HTx with suffi cient level of safety. Due to high level of DTCA using of hearts from such donors is preferable for completing urgent HTx to recipients 1А–В UNOS.

  6. Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy

    Science.gov (United States)

    Pande, Ashvin N.; Kohler, Rainer; Aikawa, Elena; Weissleder, Ralph; Jaffer, Farouc

    2006-03-01

    Molecular and cellular mechanisms of atherogenesis and its treatment are largely being unraveled by in vitro techniques. We describe methodology to directly image macrophage cell activity in vivo in a murine model of atherosclerosis using laser scanning fluorescence microscopy (LSFM) and a macrophage-targeted, near-infrared fluorescent (NIRF) magnetofluorescent nanoparticle (MFNP). Atherosclerotic apolipoprotein E deficient (apoE -/-) mice (n=10) are injected with MFNP or 0.9% saline, and wild-type mice (n=4) are injected with MFNP as additional controls. After 24 h, common carotid arteries are surgically exposed and prepared for LSFM. Multichannel LSFM of MFNP-enhanced carotid atheroma (5×5-µm in-plane resolution) shows a strong focal NIRF signal, with a plaque target-to-background ratio of 3.9+/-1.8. Minimal NIRF signal is observed in control mice. Spectrally resolved indocyanine green (ICG) fluorescence angiograms confirm the intravascular location of atheroma. On ex vivo fluorescence reflectance imaging, greater NIRF plaque signal is seen in apoE -/- MFNP mice compared to controls (p<0.01). The NIRF signal correlates well with immunostained macrophages, both by stained surface area (r=0.77) and macrophage number (r=0.86). The validated experimental methodology thus establishes a platform for investigating macrophage activity in atherosclerosis in vivo, and has implications for the detection of clinical vulnerable plaques.

  7. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

    Directory of Open Access Journals (Sweden)

    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  8. Multimodal chemical imaging of molecular messengers in emerging Pseudomonas aeruginosa bacterial communities.

    Science.gov (United States)

    Baig, Nameera F; Dunham, Sage J B; Morales-Soto, Nydia; Shrout, Joshua D; Sweedler, Jonathan V; Bohn, Paul W

    2015-10-07

    Two label-free molecular imaging techniques, confocal Raman microscopy (CRM) and secondary ion mass spectrometry (SIMS), are combined for in situ characterization of the spatiotemporal distributions of quinolone metabolites and signaling molecules in communities of the pathogenic bacterium Pseudomonas aeruginosa. Dramatic molecular differences are observed between planktonic and biofilm modes of growth for these bacteria. We observe patterned aggregation and a high abundance of N-oxide quinolines in early biofilms and swarm zones of P. aeruginosa, while the concentrations of these secreted components in planktonic cells and agar plate colonies are below CRM and SIMS detection limits. CRM, in conjunction with principal component analysis (PCA) is used to distinguish between the two co-localized isomeric analyte pairs 4-hydroxy-2-heptylquinoline-N-oxide (HQNO)/2-heptyl-3-hydroxyquinolone (PQS) and 4-hydroxy-2-nonylquinoline-N-oxide (NQNO)/2-nonyl-hydroxyquinolone (C9-PQS) based on differences in their vibrational fingerprints, illustrating how the technique can be used to guide tandem-MS and tandem-MS imaging analysis. Because N-oxide quinolines are ubiquitous and expressed early in biofilms, these analytes may be fundamentally important for early biofilm formation and the growth and organization of P. aeruginosa microbial communities. This study underscores the advantages of using multimodal molecular imaging to study complex biological systems.

  9. Imaging and measuring the molecular force of lymphoma pathological cells using atomic force microscopy.

    Science.gov (United States)

    Li, Mi; Xiao, Xiubin; Liu, Lianqing; Xi, Ning; Wang, Yuechao; Dong, Zaili; Zhang, Weijing

    2013-01-01

    Atomic force microscopy (AFM) provides a new technology to visualize the cellular topography and quantify the molecular interactions at nanometer spatial resolution. In this work, AFM was used to image the cellular topography and measure the molecular force of pathological cells from B-cell lymphoma patients. After the fluorescence staining, cancer cells were recognized by their special morphological features and then the detailed topography was visualized by AFM imaging. The AFM images showed that cancer cells were much rougher than healthy cells. CD20 is a surface marker of B cells and rituximab is a monoclonal antibody against CD20. To measure the CD20-rituximab interaction forces, the polyethylene glycol (PEG) linker was used to link rituximab onto the AFM tip and the verification experiments of the functionalized probe indicated that rituximab molecules were successfully linked onto the AFM tip. The CD20-rituximab interaction forces were measured on about 20 pathological cells and the force measurement results indicated the CD20-rituximab binding forces were mainly in the range of 110-120 pN and 130-140 pN. These results can improve our understanding of the topography and molecular force of lymphoma pathological cells. © Wiley Periodicals, Inc.

  10. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  11. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    Science.gov (United States)

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  12. Single-cell imaging of mechanotransduction in endothelial cells.

    Science.gov (United States)

    Lu, Shaoying; Wang, Yingxiao

    2014-01-01

    Endothelial cells (ECs) are constantly exposed to chemical and mechanical microenvironment in vivo. In mechanotransduction, cells can sense and translate the extracellular mechanical cues into intracellular biochemical signals, to regulate cellular processes. This regulation is crucial for many physiological functions, such as cell adhesion, migration, proliferation, and survival, as well as the progression of disease such as atherosclerosis. Here, we overview the current molecular understanding of mechanotransduction in ECs associated with atherosclerosis, especially those in response to physiological shear stress. The enabling technology of live-cell imaging has allowed the study of spatiotemporal molecular events and unprecedented understanding of intracellular signaling responses in mechanotransduction. Hence, we also introduce recent studies on mechanotransduction using single-cell imaging technologies. © 2014 Elsevier Inc. All rights reserved.

  13. Multiscale BerEp4 Molecular Imaging of Microtumor Phantoms: Toward Theranostics for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bahar Dasgeb

    2014-08-01

    Full Text Available Basal cell carcinoma (BCC, the most common cancer in humans, appears macroscopically and microscopically similar to many other skin lesions, which makes differential diagnosis difficult. We are developing an approach for quantitative molecular imaging of BerEP4, a transmembrane biomarker for BCC, with the goal of increasing the precision and accuracy of diagnosis. This pilot study was conducted to assess the affinity and selectivity of BerEp4 antibody and assess its possible use in designing theranostic probes for BCC. We provide evidence that our photon-counting fluorescence macrodetection system can recover specific signal increases from a film/pellet phantom. Additionally, we show that a two-photon excited fluorescence /backscatter confocal microscopy system can image BerEP4 antibody/antigen complex on the surface of BerEP4-expressing cancer cells in three dimensions. Based on the initial results, BerEP4 seems to be a promising biomarker for molecular imaging of BCC. To prepare BerEP4 for eventual theranostic use, we examined the feasibility of a combined macro-/micro-optical approach to imaging BCC with various histologies. These optical methods, endowed with the ability to monitor treatment in real time, may open an opportunity for noninvasive diagnosis, treatments, and follow-up.

  14. Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging

    Science.gov (United States)

    Tichauer, Kenneth M.; Samkoe, Kimberley S.; Gunn, Jason R.; Kanick, Stephen C.; Hoopes, P. Jack; Barth, Richard J.; Kaufman, Peter A.; Hasan, Tayyaba; Pogue, Brian W.

    2014-01-01

    Lymph node biopsy (LNB) is employed in many cancer surgeries to identify metastatic disease and stage the cancer, yet morbidity and diagnostic delays associated with LNB could be avoided if non-invasive imaging of nodal involvement was reliable. Molecular imaging has potential in this regard; however, variable delivery and nonspecific uptake of imaging tracers has made conventional approaches ineffective clinically. A method of correcting for non-specific uptake with injection of a second untargeted tracer is presented, allowing tumor burden in lymph nodes to be quantified. The approach was confirmed in an athymic mouse model of metastatic human breast cancer targeting epidermal growth factor receptor, a cell surface receptor overexpressed by many cancers. A significant correlation was observed between in vivo (dual-tracer) and ex vivo measures of tumor burden (r = 0.97, p < 0.01), with an ultimate sensitivity of approximately 200 cells (potentially more sensitive than conventional LNB). PMID:25344739

  15. Synthesis and Bioconjugation of Gold Nanoparticles as Potential Molecular Probes for Light-Based Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Raja Gopal Rayavarapu

    2007-01-01

    Full Text Available We have synthesized and characterized gold nanoparticles (spheres and rods with optical extinction bands within the “optical imaging window.” The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging techniques. Further, we have conjugated these gold nanoparticles to a mouse monoclonal antibody specific to HER2 overexpressing SKBR3 breast carcinoma cells. The bioconjugation protocol uses noncovalent modes of binding based on a combination of electrostatic and hydrophobic interactions of the antibody and the gold surface. We discuss various aspects of the synthesis and bioconjugation protocols and the characterization results of the functionalized nanoparticles. Some proposed applications of these potential molecular probes in the field of biomedical imaging are also discussed.

  16. Development of a compact scintillator-based high-resolution Compton camera for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kishimoto, A., E-mail: daphne3h-aya@ruri.waseda.jp [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Kataoka, J.; Koide, A.; Sueoka, K.; Iwamoto, Y.; Taya, T. [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Ohsuka, S. [Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu, Shizuoka (Japan)

    2017-02-11

    The Compton camera, which shows gamma-ray distribution utilizing the kinematics of Compton scattering, is a promising detector capable of imaging across a wide range of energy. In this study, we aim to construct a small-animal molecular imaging system in a wide energy range by using the Compton camera. We developed a compact medical Compton camera based on a Ce-doped Gd{sub 3}Al{sub 2}Ga{sub 3}O{sub 12} (Ce:GAGG) scintillator and multi-pixel photon counter (MPPC). A basic performance confirmed that for 662 keV, the typical energy resolution was 7.4 % (FWHM) and the angular resolution was 4.5° (FWHM). We then used the medical Compton camera to conduct imaging experiments based on a 3-D imaging reconstruction algorithm using the multi-angle data acquisition method. The result confirmed that for a {sup 137}Cs point source at a distance of 4 cm, the image had a spatial resolution of 3.1 mm (FWHM). Furthermore, we succeeded in producing 3-D multi-color image of different simultaneous energy sources ({sup 22}Na [511 keV], {sup 137}Cs [662 keV], and {sup 54}Mn [834 keV]).

  17. Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2016-01-01

    Full Text Available Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging.

  18. [Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

    Science.gov (United States)

    Kohara, Katsuhiko

    2014-10-01

    Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

  19. Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2

    Directory of Open Access Journals (Sweden)

    Jaeil Kim

    2017-10-01

    Full Text Available A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2 is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti–CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09 ± 0.42; P < .001. CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2–positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2–targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.

  20. In vivo 3D molecular imaging with BIRDS at high spatiotemporal resolution

    Science.gov (United States)

    Coman, Daniel; de Graaf, Robin A.; Rothman, Douglas L.; Hyder, Fahmeed

    2013-01-01

    Spectroscopic signals which emanate from complexes between paramagnetic lanthanide III ions (e.g., Tm3+) and macrocyclic chelates (e.g., 1,4,7,10-tetramethyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, or DOTMA4−) are sensitive to physiology (e.g., temperature and/or pH). Because non-exchanging protons from these lanthanide-based macrocyclic agents have relaxation times on the order of a few milliseconds, rapid data acquisition is possible with chemical shift imaging (CSI). Thus Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) which originate from non-exchanging protons of these paramagnetic agents, but exclude water proton detection, can allow molecular imaging. Previous 2D CSI experiments with such lanthanide-based macrocyclics allowed acquisition from ~12 µL voxels in rat brain within 5 minutes using rectangular encoding of k-space. Because cubical encoding of k-space in 3D for whole brain coverage increases CSI acquisition time to several tens of minutes or more, a faster CSI technique is required for BIRDS to be of practical use. Here we demonstrate a CSI acquisition method to improve 3D molecular imaging capabilities with lanthanide-based macrocyclics. Using TmDOTMA−, we show datasets from a 20×20×20 mm3 field-of-view with voxels of ~1 µL effective volume acquired within 5 minutes (at 11.7T) for temperature mapping. By employing reduced spherical encoding with Gaussian weighting (RESEGAW) instead of cubical encoding of k-space, a significant increase in CSI signal is obtained. In vitro and in vivo 3D CSI data with TmDOTMA−, and presumably similar lanthanide-based macrocyclics, suggest that acquisition using RESEGAW can be used for high spatiotemporal molecular mapping with BIRDS. PMID:23881869

  1. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Niccolini, Flavia; Politis, Marios [Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King' s College London, London (United Kingdom)

    2016-11-15

    To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded. Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA{sub A} receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA{sub A} receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients. PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments. (orig.)

  2. Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

    2017-01-30

    Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit.

  3. Molecular imaging of cannabis leaf tissue with MeV-SIMS method

    Science.gov (United States)

    Jenčič, Boštjan; Jeromel, Luka; Ogrinc Potočnik, Nina; Vogel-Mikuš, Katarina; Kovačec, Eva; Regvar, Marjana; Siketić, Zdravko; Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož

    2016-03-01

    To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

  4. Molecular imaging of cannabis leaf tissue with MeV-SIMS method

    Energy Technology Data Exchange (ETDEWEB)

    Jenčič, Boštjan, E-mail: bostjan.jencic@ijs.si [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Jeromel, Luka [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Ogrinc Potočnik, Nina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); M4I, Maastricht University, Peter Debijelaan 25A, 6229 HX Maastricht (Netherlands); Vogel-Mikuš, Katarina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Kovačec, Eva; Regvar, Marjana [University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Siketić, Zdravko [Ruđer Bošković Institute, P.O. Box 180, 10000 Zagreb (Croatia); Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia)

    2016-03-15

    To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

  5. Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, B A; Haag, M A; Stoldt, C R [Department of Mechanical Engineering, University of Colorado, Boulder, CO 80309-0427 (United States); Serkova, N J [Department of Anesthesiology, Biomedical MRI/MRS Cancer Center Core, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045 (United States); Shroyer, K R [Department of Pathology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045 (United States)], E-mail: conrad.stoldt@colorado.edu

    2008-07-02

    A method for synthesizing superparamagnetic iron oxide (SPIO) multi-nanoparticle aggregates as molecular magnetic resonance imaging (MRI) contrast agents is described. The approach utilizes organic acid/base interactions in the colloid to induce highly controllable nanoparticle aggregation. Monodisperse aggregates with diameters as large as 100 nm are synthesized by manipulating the interfacial surface chemistry of the SPIO nanoparticles in tetrahydrofuran solvent. Subsequent phospholipid micelle encapsulation yields micellar multi-SPIO (mmSPIO) aggregates with enhanced T{sub 2} relaxivity (368.0 s{sup -1} mmol{sup -1} Fe) as compared to micellar single particle SPIO (302.0 s{sup -1} mmol{sup -1} Fe). mmSPIO conjugated to anti-CA125 monoclonal antibodies were incubated with ovarian carcinoma cell lines to demonstrate targeted in vitro molecular MRI, resulting in a 66% shortening in T{sub 2} time for CA125 positive NIH:OVCAR-3 cells and a less than 3% change in T{sub 2} time for CA125 negative SK-OV-3 cells. The controllable aggregation of mmSPIO shows potential for the development of molecular MRI contrast agents with optimal sizes for specific diagnostic imaging applications.

  6. Laser Coulomb Explosion Imaging of molecular dynamics in CO2 molecule

    Science.gov (United States)

    Legare, Francois; Bocharova, Irina; Litvinyuk, Igor; Sanderson, Joseph; Karimi, Reza

    2009-05-01

    Molecular structure dynamics and dissociation pathways of CO2 molecule initiated by interaction with strong laser field were investigated by Laser Coulomb Explosion Imaging (LCEI) technique. Momentum imaging of ions in tree-body fragmentation break-up channels O^++C^++O^+ (1,1,1) and O^2++C^2++O^2+ (2,2,2) was used to determine full geometry of CO2 ionic states before explosion. Varying laser pulse length from sub-7 fs to 200 fs at the same laser field intensity we were able to follow the evolution of the molecular structure and observe dramatic change in total kinetic energy of O^2++C^2++O^2+ channel with increasing pulse length. We observed significantly bent structure of parent ion and low kinetic energy of the (2,2,2) channel for long pulses, compared to the very close to linear geometry, and very high kinetic energy for sub-7 fs laser pulse. This observation supports the idea that a phenomenon known as enhanced ionization takes place for CO2 molecule with the same mechanism as in hydrogen molecule. It also lets us put temporal and spatial limits on this process, and in the future, probing molecular structure within the critical distance range, establish connection between changing geometry and dissociation pathways.

  7. Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

    2015-04-01

    The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Impairment of retrograde neuronal transport in oxaliplatin-induced neuropathy demonstrated by molecular imaging.

    Directory of Open Access Journals (Sweden)

    Dawid Schellingerhout

    Full Text Available BACKGROUND AND PURPOSE: The purpose of our study was to utilize a molecular imaging technology based on the retrograde axonal transport mechanism (neurography, to determine if oxaliplatin-induced neurotoxicity affects retrograde axonal transport in an animal model. MATERIALS AND METHODS: Mice (n = 8/group were injected with a cumulative dose of 30 mg/kg oxaliplatin (sufficient to induce neurotoxicity or dextrose control injections. Intramuscular injections of Tetanus Toxin C-fragment (TTc labeled with Alexa 790 fluorescent dye were done (15 ug/20 uL in the left calf muscles, and in vivo fluorescent imaging performed (0-60 min at baseline, and then weekly for 5 weeks, followed by 2-weekly imaging out to 9 weeks. Tissues were harvested for immunohistochemical analysis. RESULTS: With sham treatment, TTc transport causes fluorescent signal intensity over the thoracic spine to increase from 0 to 60 minutes after injection. On average, fluorescence signal increased 722%+/-117% (Mean+/-SD from 0 to 60 minutes. Oxaliplatin treated animals had comparable transport at baseline (787%+/-140%, but transport rapidly decreased through the course of the study, falling to 363%+/-88%, 269%+/-96%, 191%+/-58%, 121%+/-39%, 75%+/-21% with each successive week and stabilizing around 57% (+/-15% at 7 weeks. Statistically significant divergence occurred at approximately 3 weeks (p≤0.05, linear mixed-effects regression model. Quantitative immuno-fluorescence histology with a constant cutoff threshold showed reduced TTc in the spinal cord at 7 weeks for treated animals versus controls (5.2 Arbitrary Units +/-0.52 vs 7.1 AU +/-1.38, p0.56, T-test. CONCLUSION: We show-for the first time to our knowledge-that neurographic in vivo molecular imaging can demonstrate imaging changes in a model of oxaliplatin-induced neuropathy. Impaired retrograde neural transport is suggested to be an important part of the pathophysiology of oxaliplatin-induced neuropathy.

  9. Image-based evaluation of the molecular events underlying HC11 mammary epithelial cell differentiation.

    Science.gov (United States)

    Shan, Liang; Zhang, Renshu; Zhang, Wanghai; Lee, Edward; Sridhar, Rajagopalan; Snyderwine, Elizabeth G; Wang, Paul C

    2008-11-15

    We have developed an image-based technique for signal pathway analysis, target validation, and compound screening related to mammary epithelial cell differentiation. This technique used the advantages of optical imaging and the HC11-Lux model system. The HC11-Lux cell line is a subclone of HC11 mammary epithelial cells transfected stably with a luciferase construct of the beta-casein gene promoter (p-344/-1betac-Lux). The promoter activity was imaged optically in real time following lactogenic induction. The imaging signal intensity was closely correlated with that measured using a luminometer following protein extraction (R=0.99, Pdifferentiation. The imaging studies showed that treatment of the cells with epidermal growth factor (EGF), AG490 (JAK2-specific inhibitor), and LY294002 (PI3K-specific inhibitor) blocked lactogenic differentiation in a dose-dependent manner. PD98059 (MEK-specific inhibitor) could reverse EGF-mediated differentiation arrest. These results indicate that these pathways are essential in cell differentiation. This simple, sensitive, and reproducible technique permits visualization and real-time evaluation of the molecular events related to milk protein production. It can be adopted for high-throughput screening of small molecules for their effects on mammary epithelial cell growth, differentiation, and carcinogenesis.

  10. Molecular cardiac PET besides FDG viability imaging; Molekulare Kardiale PET jenseits der FDG-Vitalitaetsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Lindner, O.; Burchert, W. [Universitaetsklinik der Ruhr-Univ. Bochum (Germany). Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabetszentrum NRW

    2009-06-15

    Molecular cardiac non F-18-FDG PET is currently based on perfusion imaging. It is of excellent diagnostic accuracy to detect coronary artery disease (CAD) and superior to perfusion SPECT. There is also evidence for its incremental prognostic value. The unique feature of PET to measure myocardial perfusion in absolute terms and in short time periods define its impact on cardiac imaging enabling both the evaluation of early changes in CAD and the accurate characterization of multivessel disease. Currently, all available PET perfusion tracers in Europe are cyclotron products. Rb-82, a generator product, is the most frequently employed perfusion tracer in the United States and cyclotron independent. This tracer has the potential to become an alternative in Europe soon. Nowadays, PET systems are manufactured as hybrid PET-CT scanners. In oncology, hybrid imaging revealed, that the combination of functional and morphological imaging is superior to the single components. In cardiology, the integration of perfusion PET imaging with CT calcium scoring and CT anatomy of the coronary arteries represents a similar constellation. Atherosclerotic plaque evaluation by combined PET-CT technique will be one of the most promising future applications with a potential immense impact on prophylaxis, diagnosis and therapy of CAD in the future. (orig.)

  11. Molecular imaging of HPMA copolymers: visualizing drug delivery in cell, mouse and man.

    Science.gov (United States)

    Lu, Zheng-Rong

    2010-02-17

    N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers and their drug conjugates are some of the most intensively investigated drug delivery systems for over 30years. Some of the HPMA copolymer drug conjugates have entered clinical trials. Various molecular imaging technologies have been used to investigate the mechanism of drug delivery with HPMA copolymers. Fluorescence imaging has been used for the study of the process of intracellular drug delivery, including cell binding, subcellular trafficking and intracellular fate, of HPMA copolymers and drug conjugates. Magnetic resonance imaging and nuclear medicine, including gamma-scintigraphy, SPECT and PET, have been used for the non-invasive visualization of pharmacokinetics, biodistribution and drug targeting efficiency of HPMA copolymers in animal models. gamma-Scintigraphy has been used to study HPMA copolymer drug conjugates in human patients. The application of imaging technologies in the study of HPMA copolymers and properties of the copolymers demonstrated by imaging is summarized in this review. Copyright 2010 Elsevier B.V. All rights reserved.

  12. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Anberitha T. Matthews

    2015-12-01

    Full Text Available Atherosclerosis is responsible for most cardiovascular disease (CVD and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG. Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.

  13. Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

    Science.gov (United States)

    Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

    2013-10-01

    Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  14. Atomic force microscopy: High resolution dynamic imaging of cellular and molecular structure in health and disease.

    Science.gov (United States)

    Taatjes, Douglas J; Quinn, Anthony S; Rand, Jacob H; Jena, Bhanu P

    2013-10-01

    The atomic force microscope (AFM), invented in 1986, and a member of the scanning probe family of microscopes, offers the unprecedented ability to image biological samples unfixed and in a hydrated environment at high resolution. This opens the possibility to investigate biological mechanisms temporally in a heretofore unattainable resolution. We have used AFM to investigate: (1) fundamental issues in cell biology (secretion) and, (2) the pathological basis of a human thrombotic disease, the antiphospholipid syndrome (APS). These studies have incorporated the imaging of live cells at nanometer resolution, leading to discovery of the "porosome," the universal secretory portal in cells, and a molecular understanding of membrane fusion from imaging the interaction and assembly of proteins between opposing lipid membranes. Similarly, the development of an in vitro simulacrum for investigating the molecular interactions between proteins and lipids has helped define an etiological explanation for APS. The prime importance of AFM in the success of these investigations will be presented in this manuscript, as well as a discussion of the limitations of this technique for the study of biomedical samples. Copyright © 2013 Wiley Periodicals, Inc.

  15. Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

    Science.gov (United States)

    Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

    2017-06-01

    Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

  16. A DICOM-based 2nd generation Molecular Imaging Data Grid implementing the IHE XDS-i integration profile.

    Science.gov (United States)

    Lee, Jasper; Zhang, Jianguo; Park, Ryan; Dagliyan, Grant; Liu, Brent; Huang, H K

    2012-07-01

    A Molecular Imaging Data Grid (MIDG) was developed to address current informatics challenges in archival, sharing, search, and distribution of preclinical imaging studies between animal imaging facilities and investigator sites. This manuscript presents a 2nd generation MIDG replacing the Globus Toolkit with a new system architecture that implements the IHE XDS-i integration profile. Implementation and evaluation were conducted using a 3-site interdisciplinary test-bed at the University of Southern California. The 2nd generation MIDG design architecture replaces the initial design's Globus Toolkit with dedicated web services and XML-based messaging for dedicated management and delivery of multi-modality DICOM imaging datasets. The Cross-enterprise Document Sharing for Imaging (XDS-i) integration profile from the field of enterprise radiology informatics was adopted into the MIDG design because streamlined image registration, management, and distribution dataflow are likewise needed in preclinical imaging informatics systems as in enterprise PACS application. Implementation of the MIDG is demonstrated at the University of Southern California Molecular Imaging Center (MIC) and two other sites with specified hardware, software, and network bandwidth. Evaluation of the MIDG involves data upload, download, and fault-tolerance testing scenarios using multi-modality animal imaging datasets collected at the USC Molecular Imaging Center. The upload, download, and fault-tolerance tests of the MIDG were performed multiple times using 12 collected animal study datasets. Upload and download times demonstrated reproducibility and improved real-world performance. Fault-tolerance tests showed that automated failover between Grid Node Servers has minimal impact on normal download times. Building upon the 1st generation concepts and experiences, the 2nd generation MIDG system improves accessibility of disparate animal-model molecular imaging datasets to users outside a molecular

  17. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    Science.gov (United States)

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID:22055501

  18. ABC transporters, atherosclerosis and inflammation.

    Science.gov (United States)

    Fitzgerald, Michael L; Mujawar, Zahedi; Tamehiro, Norimasa

    2010-08-01

    Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1

  19. A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Susu, E-mail: susu.yan@duke.edu; Tough, MengHeng [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Bowsher, James; Yin, Fang-Fang [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 and Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Cheng, Lin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2014-11-01

    Purpose: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom{sup TM}), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the

  20. A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems.

    Science.gov (United States)

    Yan, Susu; Bowsher, James; Tough, MengHeng; Cheng, Lin; Yin, Fang-Fang

    2014-11-01

    To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom(TM)), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the pinhole region-of-interest imaging