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Sample records for auf molecular imaging

  1. 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.)

  2. Cardiovascular molecular MR imaging

    OpenAIRE

    Lamb, H J; van der Meer, R. W.; Roos, A. (Anna); Bax, J J

    2007-01-01

    Introduction Cardiovascular molecular imaging is a rapidly evolving field of research, aiming to image and quantify molecular and cellular targets in vivo. MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging. Until now, only a limited number of studies have been published on cardiovascular molecular imaging using MR imaging. Review In the current review, MR techniques that have already shown potential are discussed. Metabolic MR imaging can ...

  3. 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.

  4. Cardiovascular Molecular Imaging

    OpenAIRE

    Khanicheh, Elham

    2009-01-01

    Although there have been significant improvements in the treatment of cardiovascular diseases they still remain the main cause of morbidity and mortality globally. Currently available diagnostic approaches may not be adequate to detect pathologic changes during the early disease stages, which may be valuable for risk stratification and also to assess a response to a therapy. Therefore molecular imaging techniques such as Contrast Enhanced Ultrasound (CEU) molecular imaging to noninvasively i...

  5. 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...

  6. 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...

  7. A Facile Approach to Fabricate Water-soluble Au-Fe3O4 Nanoparticle for Liver Cancer Cells Imaging

    Institute of Scientific and Technical Information of China (English)

    梁重时; 吴献荣; 谢叶归; 刘顺英

    2012-01-01

    Au-Fe3O4 nanoparticles were widely used as nanoplatforms for biologic applications through readily further functionalization. Dopamine (DA)-coated superparamagnetic iron oxide (SPIO) nanoparticles (DA@Fe3O4) have been successfully synthesized using a one-step process by modified coprecipitation method. Then 2--3 nm gold nanoparticles were easily conjugated to DA@Fe3O4 nanoparticles by the electrostatic force between gold nanoparti- cles and amino groups of dopamine to afford water-soluble Au-Fe3O4 hybrid nanoparticles. A detailed investigation by dynamic light scatting (DLS), transmission electron microscopy (TEM), fourier transform infrared (FT-IR) and X-ray diffraction (XRD) were performed in order to characterize the physicochemical properties of the hybrid nanoparticles. The hybrid nanoparticles were easily functionalized with a targeted small peptide A54 (AGKGTPSLETTP) and fluorescence probe fluorescein isothiocyanate (FITC) for liver cancer cell BEL-7402 imaging. This simple approach to prepare hybrid nanoparticles provides a facile nanoplatform for muti-functional derivations and may be extended to the immobilization of other metals or bimolecular on SPIO surface.

  8. Molecular breast imaging. An update

    International Nuclear Information System (INIS)

    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 (1H-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 (23Na-MRI), phosphorus spectroscopy (31P-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.)

  9. Time-resolved molecular imaging

    Science.gov (United States)

    Xu, Junliang; Blaga, Cosmin I.; Agostini, Pierre; DiMauro, Louis F.

    2016-06-01

    Time-resolved molecular imaging is a frontier of ultrafast optical science and physical chemistry. In this article, we review present and future key spectroscopic and microscopic techniques for ultrafast imaging of molecular dynamics and show their differences and connections. The advent of femtosecond lasers and free electron x-ray lasers bring us closer to this goal, which eventually will extend our knowledge about molecular dynamics to the attosecond time domain.

  10. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  11. Molecular imaging in oncology

    OpenAIRE

    Dzik-Jurasz, A S K

    2004-01-01

    Cancer is a genetic disease that manifests in loss of normal cellular homeostatic mechanisms. The biology and therapeutic modulation of neoplasia occurs at the molecular level. An understanding of these molecular processes is therefore required to develop novel prognostic and early biomarkers of response. In addition to clinical applications, increased impetus for the development of such technologies has been catalysed by pharmaceutical companies investing in the development of molecular ther...

  12. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  13. Molecular imaging with terahertz waves.

    Science.gov (United States)

    Oh, Seung Jae; Choi, Jihye; Maeng, Inhee; Park, Jae Yeon; Lee, Kwangyeol; Huh, Yong-Min; Suh, Jin-Suck; Haam, Seungjoo; Son, Joo-Hiuk

    2011-02-28

    We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

  14. Advances in Multimodality Molecular Imaging

    International Nuclear Information System (INIS)

    Multimodality molecular imaging is now playing a pivotal role in clinical setting and biomedical research. Modern molecular imaging technologies are deemed to potentially lead to a revolutionary paradigm shift in healthcare and revolutionize clinical practice. Within the spectrum of macroscopic medical imaging, sensitivity ranges from the detection of millimolar to submillimolar concentrations of contrast media with computed tomography (CT) and magnetic resonance imaging (MRI), respectively, to picomolar concentrations in single-photon emission computed tomography (SPECT) and positron emission 8 9 tomography (PET): a 108-109 difference. Even though the introduction of dedicated dual-modality imaging systems designed specifically and available commercially for clinical practice is relatively recent, the concept of combining anatomical and functional imaging has been recognized for several decades. Software- and hardware-based correlation between anatomical (x-ray CT, MRI) and physiological (PET) information is a promising research field and now offers unique capabilities for the medical imaging community and biomedical researchers. The introduction of dual-modality PET/CT imaging systems in clinical environments has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a 'one-stop shop' and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging where the first patient images have been shown late in 2006. This paper discusses the

  15. 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.

  16. Molecular imaging in cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Mark H. [Stanford University School of Medicine, Stanford, CA (United States); Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States)

    2011-02-15

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  17. 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.

  18. 3D molecular imaging SIMS

    Energy Technology Data Exchange (ETDEWEB)

    Gillen, Greg [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)]. E-mail: Greg.gillen@nist.gov; Fahey, Albert [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Wagner, Matt [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Mahoney, Christine [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)

    2006-07-30

    Thin monolayer and bilayer films of spin cast poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), poly(lactic) acid (PLA) and PLA doped with several pharmaceuticals have been analyzed by dynamic SIMS using SF{sub 5} {sup +} polyatomic primary ion bombardment. Each of these systems exhibited minimal primary beam-induced degradation under cluster ion bombardment allowing molecular depth profiles to be obtained through the film. By combing secondary ion imaging with depth profiling, three-dimensional molecular image depth profiles have been obtained from these systems. In another approach, bevel cross-sections are cut in the samples with the SF{sub 5} {sup +} primary ion beam to produce a laterally magnified cross-section of the sample that does not contain the beam-induced damage that would be induced by conventional focussed ion beam (FIB) cross-sectioning. The bevel surface can then be examined using cluster SIMS imaging or other appropriate microanalysis technique.

  19. Molecular Imaging of the Kidneys

    Science.gov (United States)

    Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

    2010-01-01

    Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer

  20. Molecular imaging: future uses in arthritides; Molekulare Bildgebung: Kuenftige Anwendungen bei Arthritiden

    Energy Technology Data Exchange (ETDEWEB)

    Brem, M.H.; Schlechtweg, P.M.; MacKenzie, J.; Winalski, C.S.; Lang, P. [Brigham and Women' s Hospital of Harvard Medical School, Department of Radiology, Boston, MA 02115 (United States)

    2006-05-15

    Molecular imaging is an upcoming field in radiology as a result of great advances in imaging technology, genetics, and biochemistry in the recent past. Early-stage imaging of molecular pathological changes in cells opens the gates to new methods in medical treatment of diseases that otherwise would only be detected in advanced stages. Methods of imaging biochemical pathways with molecular agents are currently an issue of intensive research. This article reviews current modalities of molecular imaging in arthritis that should offer future perspective on early disease detection, diagnosis, and monitoring of treatment efficiency and how they can pave the way to optimized therapy. (orig.) [German] Die molekulare Bildgebung gehoert dank immenser Fortschritte bzgl. Technologie, Genetik und Biochemie in juengster Vergangenheit zu den sehr viel versprechenden neuen Methoden der Bildgebung in der Radiologie. Die Darstellung pathophysiologischer Vorgaenge auf molekularer Ebene in Initialstadien von Erkrankungen eroeffnen ganz neue und noch weitgehend unerforschte Optionen bei der Behandlung von Erkrankungen, die mit herkoemmlichen Methoden erst in weit fortgeschrittenen Stadien erkannt werden koennen. Gegenwaertig wird intensiv an Methoden zur Darstellung dieser verschiedenen zellulaeren Vorgaenge durch Kontrastmittel auf molekularer Basis gearbeitet. In diesem Uebersichtsartikel soll veranschaulicht werden, wie die molekulare Bildgebung bei Arthritiden derzeit und zukuenftig zu verbesserter Frueherkennung, Diagnostik und durch Monitoring der verschiedenen Behandlungsregime zu optimierter Therapie beitragen kann. (orig.)

  1. Advances in multimodality molecular imaging

    Directory of Open Access Journals (Sweden)

    Zaidi Habib

    2009-01-01

    Full Text Available Multimodality molecular imaging using high resolution positron emission tomography (PET combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT and functional or metabolic (PET information provided in a "one-stop shop" and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed.

  2. Sparse image reconstruction for molecular imaging

    CERN Document Server

    Ting, Michael; Hero, Alfred O

    2008-01-01

    The application that motivates this paper is molecular imaging at the atomic level. When discretized at sub-atomic distances, the volume is inherently sparse. Noiseless measurements from an imaging technology can be modeled by convolution of the image with the system point spread function (psf). Such is the case with magnetic resonance force microscopy (MRFM), an emerging technology where imaging of an individual tobacco mosaic virus was recently demonstrated with nanometer resolution. We also consider additive white Gaussian noise (AWGN) in the measurements. Many prior works of sparse estimators have focused on the case when H has low coherence; however, the system matrix H in our application is the convolution matrix for the system psf. A typical convolution matrix has high coherence. The paper therefore does not assume a low coherence H. A discrete-continuous form of the Laplacian and atom at zero (LAZE) p.d.f. used by Johnstone and Silverman is formulated, and two sparse estimators derived by maximizing t...

  3. Molecular and Functional Imaging of Internet Addiction

    OpenAIRE

    Yunqi Zhu; Hong Zhang; Mei Tian

    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) an...

  4. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    OpenAIRE

    Lee, Soo Jin; Paeng, Jin Chul

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell...

  5. 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.

  6. Nanodiamond Imaging: a New Molecular Imaging Approach

    OpenAIRE

    Hegyi, Alex Nathan

    2013-01-01

    Nanodiamond imaging is a novel biomedical imaging technique that non-invasively records the distribution of biologically-tagged nanodiamonds in vivo, in two or three dimensions. A nanodiamond imaging system optically detects electron spin resonance of nitrogen-vacancy centers in nanodiamonds, a non-toxic nanomaterial that is easily biologically functionalized. Two systems were built to demonstrate the feasibility of the technique. Using the first system, we imaged 2D projections of multipl...

  7. Molecular imaging of mental disorders

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) techniques have made it possible to measure changes in neurochemical components in living human brain. PET can be used to investigate various brain functions such as receptors, transporters, enzymes and various biochemical pathways; therefore, it could be a powerful tool for molecular imaging of mental disorders. Since the pathophysiology of schizophrenia has been discussed with a functional alteration of dopaminergic transmission in the brain, we have focused the dopaminergic components for the research target of schizophrenia using PET. Using high affinity ligand [11C]FLB 457, we found reduced D2 receptor binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D2 receptor binding and the positive symptom score. Subregions of interest were defined on the thalamus using individual magnetic resonance images. D2 receptor binding was also lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. On the other hand D1 receptor binding was found to be lower in the prefrontal cortex and a significant negative correlation was observed between D1 receptor binding and the negative symptom score. Abnormality of D1 receptor function would be at the bottom of the negative symptoms and cognitive impairment of schizophrenia. Regarding the effect of antipsychotics on dopamine D2 receptor, occupancy and it's time-course have been measured in a living body using PET. This approach can provide in vivo pharmacological evidences of antipsychotics and establish the rational therapeutic strategy. PET is a powerful tool not only in the field of brain research but also drug discovery. (author)

  8. Molecular Imaging of Pulmonary Cancer and Inflammation

    OpenAIRE

    Divgi, Chaitanya R.

    2009-01-01

    Molecular imaging (MI) may be defined as imaging in vivo using molecules that report on biologic function. This review will focus on the clinical use of radioactive tracers (nonpharmacologic amounts of compounds labeled with a radioactive substance) that permit external imaging using single photon emission computed tomography (planar, SPECT) or positron emission tomography (PET) imaging. Imaging of lung cancer has been revolutionized with the use of fluorine-18–labeled fluorodeoxyglucose (18F...

  9. Principle and applications of terahertz molecular imaging.

    Science.gov (United States)

    Son, Joo-Hiuk

    2013-05-31

    The principle, characteristics and applications of molecular imaging with terahertz electromagnetic waves are reviewed herein. The terahertz molecular imaging (TMI) technique uses nanoparticle probes to achieve dramatically enhanced sensitivity compared with that of conventional terahertz imaging. Surface plasmons, induced around the nanoparticles, raise the temperature of water in biological cells, and the temperature-dependent changes in the optical properties of water, which are large in the terahertz range, are measured differentially by terahertz waves. TMI has been applied to cancer diagnosis and nanoparticle drug delivery imaging. The technique is also compared with magnetic resonance imaging by using a dual-modality nanoparticle probe.

  10. Molecular imaging in quality health care

    International Nuclear Information System (INIS)

    Full text: Quality health care results from translating fundamental bench discoveries and making them available to patients. During the past decade, 'molecular imaging' has emerged both as a new tool/technology and as a research and clinical discipline. Molecular imaging is an interdisciplinary approach involving biologists, physicists, physicians, mathematicians, conventional chemists, radiochemists and other specialists who have joined forces for better understanding and visualizing of both normal physiological processes and the molecular processes preceding the morphological manifestations of disease in vivo. Molecular imaging has been defined as 'non-invasive, quantitative, and repetitive imaging of targeted macromolecules and biological processes in living organisms' or as 'the visual representation, characterization, and quantification of biological processes at the cellular and sub-cellular levels within intact living organisms'. Weissleder defined molecular imaging in the most simple terms as 'studying diseases non-invasively at the molecular level'. Regardless of these semantic differences molecular imaging can contribute significantly to the preclinical and clinical drug and disease evaluation process. It is interesting to note, that despite major advances in imaging technology, cancer mortality has remained largely unchanged over the last three decades. Imaging has thus far enabled us to look through a magnifying glass at disease processes but has failed to dramatically influence disease outcomes. Emerging data suggest that molecular PET imaging is about to change this situation. High resolution molecular imaging devices designed for small animal research have developed into valuable tools for drug evaluation and imaging probe design. These include microPET, microCT, microMRI and optical imaging devices. These have enabled us to study drug effects in vivo by monitoring longitudinally their effects on tumour cell metabolism or proliferation. The only

  11. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Progress of molecular biology, genetic engineering, and polymer chemistry provide various tools to target molecules and cells in vivo. In this paper, recent achievements in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune, and stem cells using molecular nuclear imaging techniques are introduced

  12. 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 radiatio

  13. Molecular Imaging of Urogenital Diseases

    Science.gov (United States)

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

    2013-01-01

    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 both clinical management and drug development. PET radiotracers beyond 18F-Fluorodeoxyglucose (FDG) for prostate cancer include 18F-Sodium Fluoride, 11C-Choline and 18F-Fluorocholine and 11C-Acetate. Other emerging and promising PET radiotracers include a synthetic L-leucine amino acid analog (anti-18F-FACBC), dihydrotestosterone analog (18F-FDHT) and prostate specific membrane antigen (PSMA) based PET radiotracers (ex. 18F-DCFBC, 89Zr-DFO-J591, 68Ga(HBED-CC)). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Renal cell cancer imaging with FDG PET/CT although available can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX) based antibody (124I-girentuximab) and radioimmunotherapy targeting with 177Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-18F-fluorohippurate (18F-PFH) and hippurate m-cyano-p-18F-fluorohippurate (18F-CNPFH) and Rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin angiotensin system with a variety of selective PET radioligands are also becoming available for clinical translation. PMID:24484747

  14. 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.

  15. Molecular and Functional Imaging of Internet Addiction

    Directory of Open Access Journals (Sweden)

    Yunqi Zhu

    2015-01-01

    Full Text Available 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.

  16. Bildungsreform auf dem Lande

    OpenAIRE

    Heckmann, Carolin

    2013-01-01

    Im Fokus der Arbeit stehen die Bildungsreformen auf dem Lande in der Zeitspanne von 1949 bis zum Ende der 1960er Jahre. Die Entwicklung der Volksschule in Nordhessen, genauer im südlichen Ringgau nahe der thüringischen Grenze, wird genauer betrachtet. Dafür wurden Schulchroniken aus dem Südringgau beschrieben und analysiert. Der Fokus liegt dabei auf der Entstehung der Mittelpunktschule Herleshausen/Nesselröden und den damit verbundenen Schließungen der einklassigen Volksschulen in den einzel...

  17. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  18. Molecular imaging of atherosclerosis in translational medicine

    Energy Technology Data Exchange (ETDEWEB)

    Perrone-Filardi, Pasquale; Costanzo, Pierluigi; Marciano, Caterina; Vassallo, Enrico; Marsico, Fabio; Ruggiero, Donatella; Petretta, Maria Piera; Chiariello, Massimo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Dellegrottaglie, Santo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Mount Sinai Medical Center, Z. and M.A. Wiener Cardiovascular Institute and M.-J. and H.R. Kravis Center for Cardiovascular Health, New York, NY (United States); Rudd, James H.F. [University of Cambridge, School of Clinical Medicine, Cambridge (United Kingdom); Cuocolo, Alberto [University Federico II, Department of Biomorphological and Functional Sciences, Naples (Italy); SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples (Italy)

    2011-05-15

    Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events. (orig.)

  19. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99mTc as a radionuclide. We developed 99mTc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99mTc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99mTc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99mTc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

  20. 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.)

  1. Quantitative cardiovascular magnetic resonance for molecular imaging

    OpenAIRE

    Lanza Gregory M; Caruthers Shelton D; Winter Patrick M; Wickline Samuel A

    2010-01-01

    Abstract Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examp...

  2. NAOMI: nanoparticle assisted optical molecular imaging

    Science.gov (United States)

    Faber, Dirk J.; van Velthoven, Mirjam E. J.; de Bruin, Martijn; Aalders, Maurice C. G.; Verbraak, Frank D.; Graf, Christina; van Leeuwen, Ton G.

    2006-02-01

    Our first steps towards nanoparticle assisted, optical molecular imaging (NAOMI) using OCT as the imaging modality are presented. We derive an expression to estimate the sensitivity of this technique. We propose to use nanoparticles based on biodegradable polymers, loaded with suitable dyes as contrast agent, and outline a method for establishing their desired optical properties prior to synthesis. This report presents preliminary results of our investigation on the use of nanoshells to serve as contrast agents We injected nanoshells with specific contrast features in the 800 nm wavelength region in excised porcine eyes. The nanoshells showed up as bright reflecting structures in the OCT images, which confirm their potential as contrast agents.

  3. Radiogenomic imaging-linking diagnostic imaging and molecular diagnostics

    Institute of Scientific and Technical Information of China (English)

    Mathias; Goyen

    2014-01-01

    Radiogenomic imaging refers to the correlation between cancer imaging features and gene expression and is one of the most promising areas within science and medicine. High-throughput biological techniques have reshaped the perspective of biomedical research allowing for fast and efficient assessment of the entire molecular topography of a cell’s physiology providing new insights into human cancers. The use of non-invasive imaging tools for gene expression profiling of solid tumors could serve as a means for linking specific imaging features with specific gene expression patterns thereby allowing for more accurate diagnosis and prognosis and obviating the need for high-risk invasive biopsy procedures. This review focuses on the medical imaging part as one of the main drivers for the development of radiogenomic imaging.

  4. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

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

    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...

  5. Dose reduction in molecular breast imaging

    Science.gov (United States)

    Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

    2011-10-01

    Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

  6. Molecular imaging in quality health care

    International Nuclear Information System (INIS)

    Full text: Quality Health Care results from applying fundamental basic science and preclinical concepts as well as novel technologies to patient care within specific socio-economic frameworks. Cancer mortality has improved recently but outcomes of cancer patients are still unacceptably poor. Molecular Imaging has the potential to improve the outcome of cancer patients in several ways. In the preclinical setting, high resolution molecular imaging devices designed for small animal research have developed into valuable tools for drug evaluation and imaging probe design. These have enabled us to study drug effects in vivo by monitoring longitudinally their effects on tumor cell metabolism or proliferation. The success of Imatinib in treating chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) has demonstrated that targeted drugs can induce remarkable tumor responses and may even cure cancer patients. Targeted drugs have been used for treating various common solid human tumors, including breast cancer, colorectal cancer, and non-small cell lung cancer. However, diverse signaling pathways are involved in the development and progression of these genetically heterogeneous diseases. Consequently, inhibition of one specific pathway is likely to be efficacious in only in small subsets of patients with specific histological tumor types. It is unlikely that a single 'blockbuster' drug can be effective for all patients with a 'common' tumor. Rather, it will be necessary to develop multiple targeted drugs even for patients that share a single histologically defined tumor type. The inevitable consequence is a decreased revenue/cost ratio for the industry and increasing costs for patients and health care systems. It is therefore of paramount importance to identify drug failure as early as possible in preclinical and clinical trials. Human studies with positron emission tomography (PET) with molecular imaging probes targeting physiological processes such as

  7. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Zhi-Yi Chen

    2014-01-01

    Full Text Available Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy.

  8. 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.

  9. NAOMI: nanoparticle-assisted optical molecular imaging

    Science.gov (United States)

    Faber, Dirk J.; de Bruin, Martijn; Aalders, Maurice C. G.; Verbraak, Frank D.; van Leeuwen, Ton G.

    2007-02-01

    We present our first steps towards nanoparticle assisted, optical molecular imaging (NAOMI) using biodegradable nanoparticles. Our focus is on using optical coherence tomography(OCT) as the imaging modality. We propose to use nanoparticles based on biodegradable polymers, loaded with carefully selected dyes as contrast agent, and outline a method for establishing their desired optical properties prior to synthesis. Moreover, we perform a qualitative pilot study using these biodegradable nanoparticles, measuring their optical properties which are found to be in line with theoretical predictions.

  10. Molecular Imaging of Biomarkers in Breast Cancer

    Science.gov (United States)

    Ulaner, Gary A.; Riedl, Chris C.; Dickler, Maura N.; Jhaveri, Komal; Pandit-Taskar, Neeta; Weber, Wolfgang

    2016-01-01

    The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials. PMID:26834103

  11. Molecular imaging for the diagnosis of dementia

    International Nuclear Information System (INIS)

    Many radiotracers have been developed to visualize pathological protein accumulation and neurotransmitter deficits in the brains of patients with dementia using positron emission tomography (PET). Recent advances in the development of β-sheet binding agents enabled in vivo detection of senile plaques in Alzheimer's disease. Molecular imaging using these agents would contribute to the early and accurate diagnosis of dementia and monitoring therapeutic effect of anti-dementia drugs. (author)

  12. 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

  13. Neutron imaging for inertial confinement fusion and molecular optic imaging

    International Nuclear Information System (INIS)

    Scientific domains that require imaging of micrometric/nano-metric objects are dramatically increasing (Plasma Physics, Astrophysics, Biotechnology, Earth Sciences...). Difficulties encountered in imaging smaller and smaller objects make this research area more and more challenging and in constant evolution. The two scientific domains, through which this study has been led, are the neutron imaging in the context of the inertial confinement fusion and the fluorescence molecular imaging. Work presented in this thesis has two main objectives. The first one is to describe the instrumentation characteristics that require such imagery and, relatively to the scientific domains considered, identify parameters likely to optimize the imaging system accuracy. The second one is to present the developed data analysis and reconstruction methods able to provide spatial resolution adapted to the size of the observed object. Similarities of numerical algorithms used in these two scientific domains, which goals are quiet different, show how micrometric/nano-metric object imaging is a research area at the border of a large number of scientific disciplines. (author)

  14. PET Imaging - from Physics to Clinical Molecular Imaging

    Science.gov (United States)

    Majewski, Stan

    2008-03-01

    From the beginnings many years ago in a few physics laboratories and first applications as a research brain function imager, PET became lately a leading molecular imaging modality used in diagnosis, staging and therapy monitoring of cancer, as well as has increased use in assessment of brain function (early diagnosis of Alzheimer's, etc) and in cardiac function. To assist with anatomic structure map and with absorption correction CT is often used with PET in a duo system. Growing interest in the last 5-10 years in dedicated organ specific PET imagers (breast, prostate, brain, etc) presents again an opportunity to the particle physics instrumentation community to contribute to the important field of medical imaging. In addition to the bulky standard ring structures, compact, economical and high performance mobile imagers are being proposed and build. The latest development in standard PET imaging is introduction of the well known TOF concept enabling clearer tomographic pictures of the patient organs. Development and availability of novel photodetectors such as Silicon PMT immune to magnetic fields offers an exciting opportunity to use PET in conjunction with MRI and fMRI. As before with avalanche photodiodes, particle physics community plays a leading role in developing these devices. The presentation will mostly focus on present and future opportunities for better PET designs based on new technologies and methods: new scintillators, photodetectors, readout, software.

  15. Molecular Imaging with Activatable Reporter Systems

    Directory of Open Access Journals (Sweden)

    Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes, the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development.

  16. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  17. Molecular imaging of apoptosis in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hakumaeki, Juhana M. [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland) and Department of Clinical Radiology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)]. E-mail: juhana.hakumaki@uku.fi; Liimatainen, Timo [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland)

    2005-11-01

    Apoptosis plays an important role in cancer. Mechanisms hindering its action are implicated in a number of malignancies. Also, the induction of apoptosis plays a pivotal role in non-surgical cancer treatment regimes such as irradiation, chemotherapy, or hormones. Recent advanced in imaging science have made it now possible for us to detect and visualize previously inaccessible and even unrecognized biological phenomena in cells and tissue undergoing apoptosis in vivo. Not only are these imaging techniques painting an intriguing picture of the spatiotemporal characteristics and metabolic and biophysical of apoptosis in situ, but they are expected to have an ever increasing impact in preclinical testing and design of new anticancer agents as well. Rapid and accurate visualization of apoptotic response in the clinical settings can also be of significant diagnostic and prognostic worth. With the advent of molecular medicine and patient-tailored treatment options and therapeutic agents, such monitoring techniques are becoming paramount.

  18. Bioresponsive probes for molecular imaging: concepts and in vivo applications

    NARCIS (Netherlands)

    Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

    2015-01-01

    Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecu

  19. 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...

  20. Current Progress of Aptamer-Based Molecular Imaging

    OpenAIRE

    Wang, Andrew Z.; Farokhzad, Omid C.

    2014-01-01

    Aptamers, single-stranded oligonucleotides, are an important class of molecular targeting ligand. Since their discovery, aptamers have been rapidly translated into clinical practice. They have been approved as therapeutics and molecular diagnostics. Aptamers also possess several properties that make them uniquely suited to molecular imaging. This review aims to provide an overview of aptamers’ advantages as targeting ligands and their application in molecular imaging.

  1. Molecular imaging probes derived from natural peptides.

    Science.gov (United States)

    Charron, C L; Hickey, J L; Nsiama, T K; Cruickshank, D R; Turnbull, W L; Luyt, L G

    2016-06-01

    Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available. PMID:26911790

  2. Photoelectron spectroscopy of self-assembled monolayers of molecular switches on noble metal surfaces; Photoelektronenspektroskopie selbstorganisierter Adsorbatschichten aus molekularen Schaltern auf Edelmetalloberflaechen

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, Nils

    2012-09-12

    Self-assembled monolayers (SAMs) of butanethiolate (C4) on single crystalline Au(111) surfaces were prepared by adsorption from solution. The thermally activated desorption behaviour of the C4 molecules from the gold substrate was examined by qualitative thermal desorption measurements (TDM), through this a desorption temperature T{sub Des}=473 K could be determined. With this knowledge, it was possible to produce samples of very good surface quality, by thermal treatment T{sub Sample}image potential states. The reversible photo- and thermally activated isomerization of the molecular switch 3-(4-(4-Hexyl-phenylazo)-phenoxy)-propane-1-thiol (ABT), deposited by self-assembly from solution on Au(111), was examined using laser-based photoelectron spectroscopy. Differences in the molecular dipole moment characteristic for the trans and the cis isomer of ABT were observed via changes in the sample work function, accessible by detection of the threshold energy for photoemission. A quantitative

  3. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    OpenAIRE

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    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.

  4. Reaktionen auf Geschmacksstoffe bei Duftstoffsensibilisierten

    OpenAIRE

    Fornoff, Nicole

    2005-01-01

    Positive Reaktionen im Epikutantest (ECT) auf den Duftstoffmix (DM) sind relativ häufig, teilweise ohne anamnestischen Bezug zu Duftstoffkontakt. Da Duftstoffe auch als Aromastoffe in Nahrungsmitteln weit verbreitet sind, wurde untersucht, ob die orale Zufuhr von Duftstoffen bei Sensibilisierten eine klinische Reaktion auslöst. Methode: 39 Personen mit einem positiven ECT auf den standartisierten 8%igen Duftstoffmix (DM) nahmen an der Studie teil. Bei allen Probanden wurde der DM und 11 Einze...

  5. Molecular breast imaging with gamma emitters.

    Science.gov (United States)

    Schillaci, O; Spanu, A; Danieli, R; Madeddu, G

    2013-12-01

    Following a diagnosis of breast cancer (BC), the early detection of local recurrence is important to define appropriate therapeutic strategies and increase the chances of a cure. In fact, despite major progress in surgical treatment, radiotherapy, and chemotherapy protocols, tumor recurrence is still a major problem. Moreover, the diagnosis of recurrence with conventional imaging methods can be difficult as a result of the presence of scar tissue. Molecular breast imaging (MBI) with gamma-ray emitting radiotracers may be very useful in this clinical setting, because it is not affected by the post-therapy morphologic changes. This review summarises the applications of 99mTc-sestamibi and 99mTc-tetrofosmin, the two most employed gamma emitter radiopharmaceuticals for MBI, in the diagnosis of local disease recurrence in patients with BC. The main limitation of MBI using conventional gamma-cameras is the low sensitivity for small BCs. The recent development of hybrid single photon emission computed tomography/computed tomography devices and especially of high-resolution specific breast cameras can improve the detection rate of sub-centimetric malignant lesions. Nevertheless, probably only the large availability of dedicated cameras will allow the clinical acceptance of MBI as useful complementary diagnostic technique in BC recurrence. The possible role of MBI with specific cameras in monitoring the local response of BC to neoadjuvant chemotherapy is also briefly discussed. PMID:24322791

  6. Applications of molecular MRI and optical imaging in cancer

    OpenAIRE

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

    2010-01-01

    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 c...

  7. Molecular imaging of stem cell transplantation for neurodegenerative diseases.

    Science.gov (United States)

    Wang, Ping; Moore, Anna

    2012-01-01

    Cell replacement therapy with stem cells holds tremendous therapeutic potential for treating neurodegenerative diseases. Over the last decade, molecular imaging techniques have proven to be of great value in tracking transplanted cells and assessing the therapeutic efficacy. This current review summarizes the role and capabilities of different molecular imaging modalities including optical imaging, nuclear imaging and magnetic resonance imaging in the field of stem cell therapy for neurodegenerative disorders. We discuss current challenges and perspectives of these techniques and encompass updated information such as theranostic imaging and optogenetics in stem cell-based treatment of neurodegenerative diseases.

  8. Molecular imaging in Libman-Sacks endocarditis.

    Science.gov (United States)

    Dahl, Anders; Schaadt, Bente K; Santoni-Rugiu, Eric; Bruun, Niels E

    2015-04-01

    We present a 54-year-old woman with systemic lupus erythematosus (SLE), fever, pericardial effusion and a mitral valve vegetation. (18)F-Fluorodesoxyglucose positron emission tomography CT ((18)F-FDG-PET-CT) showed very high accumulation of the isotope at the mitral valve. The patient underwent 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 demonstrated the increased glucose uptake caused by infiltrating white blood cells in the ongoing inflammatory process at the mitral valve. In conclusion, (18)F-FDG-PET-CT cannot be used to distinguish between IE and non-infective Libman-Sacks vegetations.

  9. Molecular imaging of macrophage enzyme activity in cardiac inflammation

    OpenAIRE

    Ali, Muhammad; Pulli, Benjamin; Chen, John W.

    2014-01-01

    Molecular imaging is highly advantageous as various insidious inflammatory events can be imaged in a serial and quantitative fashion. Combined with the conventional imaging modalities like computed tomography (CT), magnetic resonance (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology, quantify inflammation and predict outcome. Macrophages are increasingly gaining importance as an imaging biomarker in inflammatory cardiovascular diseases. Macrophages, recruited to th...

  10. Functional and molecular image guidance in radiotherapy treatment planning optimization.

    Science.gov (United States)

    Das, Shiva K; Ten Haken, Randall K

    2011-04-01

    Functional and molecular imaging techniques are increasingly being developed and used to quantitatively map the spatial distribution of parameters, such as metabolism, proliferation, hypoxia, perfusion, and ventilation, onto anatomically imaged normal organs and tumor. In radiotherapy optimization, these imaging modalities offer the promise of increased dose sparing to high-functioning subregions of normal organs or dose escalation to selected subregions of the tumor as well as the potential to adapt radiotherapy to functional changes that occur during the course of treatment. The practical use of functional/molecular imaging in radiotherapy optimization must take into cautious consideration several factors whose influences are still not clearly quantified or well understood including patient positioning differences between the planning computed tomography and functional/molecular imaging sessions, image reconstruction parameters and techniques, image registration, target/normal organ functional segmentation, the relationship governing the dose escalation/sparing warranted by the functional/molecular image intensity map, and radiotherapy-induced changes in the image intensity map over the course of treatment. The clinical benefit of functional/molecular image guidance in the form of improved local control or decreased normal organ toxicity has yet to be shown and awaits prospective clinical trials addressing this issue. PMID:21356479

  11. Inversion of Strong Field Photoelectron Spectra for Molecular Orbital Imaging

    CERN Document Server

    Puthumpally-Joseph, R; Peters, M; Nguyen-Dang, T T; Atabek, O; Charron, E

    2016-01-01

    Imaging structures at the molecular level is a fast developing interdisciplinary research field that spans across the boundaries of physics and chemistry. High spatial resolution images of molecules can be obtained with photons or ultrafast electrons. In addition, images of valence molecular orbitals can be extracted via tomographic techniques based on the coherent XUV radiation emitted by a molecular gas exposed to an intense ultra-short infrared laser pulse. In this paper, we demonstrate that similar information can be obtained by inverting energy resolved photoelectron spectra using a simplified analytical model.

  12. Designing an university-level module on molecular imaging chemistry

    International Nuclear Information System (INIS)

    Full text: Why do we need radiopharmacy, radiopharmacy, radiopharmacy training? In this post-genomic era, molecular imaging has gain tremendous interest not only amongst physicians but also from biologists, chemists, physicists, engineers, statisticians, pharmaceutical companies and even from governments. There is no doubt that nuclear medicine has been engaged in molecular medicine more than one decade ago. Positron emission tomography (PET) has reawaken interest in long forgotten radiopharmacy. Only major hospitals in the developed countries have invested in the development of dedicated radiopharmacy laboratory and training or recruitment of radiopharmacist. But PET has forced nuclear medicine to create a radiopharmacy unit and adopt radiopharmacy guidelines such as good radiopharmaceutical practice (GRPP) and good manufacturing practice (GMP). It is compounded by the fact that SPECT radiopharmaceutical chemistry has advanced significantly for both diagnostics and therapeutics, which calls for a high level of understanding on radiopharmaceutical chemistry and technical know-how. These factors eventually lead to introduction of tran ing program, courses and degree program. The most striking examples will be European Association of Nuclear Medicine (EANM) radiopharmacy courses and a series of IAEA activities on GRPP, GMP and technologist training programs. Various forms of training or education program can be formulated for various levels, starting from basic radiopharmacy course to PhD program, depending on the following factors; (1) National interest and policies on bio/medical sector; (2) Size of the nuclear medicine community in the respective country; (3) Institution interest and policies; and (4) Existing infrastructure and programs. Current Radiopharmacy Education in Singapore: In Singapore, all of the major nuclear medicine centers are supervised by radiopharmacists with PhD degree. All of the nuclear medicine technologists in the major centers have got

  13. 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...

  14. Imaging the Breakdown of Molecular Frame Dynamics through Rotational Uncoupling

    CERN Document Server

    Zipp, Lucas J; Bucksbaum, Philip H

    2016-01-01

    We have observed directly in the time domain the uncoupling of electron motion from the molecular frame due to rotational-electronic coupling in a molecular Rydberg system. In contrast to Born- Oppenheimer dynamics, in which the electron is firmly fixed to the molecular frame, there exists a regime of molecular dynamics known as $l$-uncoupling where the motion of a non-penetrating Rydberg electron decouples from the instantaneous alignment of the molecular frame. We have imaged this unusual regime in time-dependent photoelectron angular distributions of a coherently prepared electron wave packet in the 4$f$ manifold of $N_2$.

  15. Continuous-terahertz-wave molecular imaging system for biomedical applications

    Science.gov (United States)

    Zhang, Rui; Zhang, Liangliang; Wu, Tong; Wang, Ruixue; Zuo, Shasha; Wu, Dong; Zhang, Cunlin; Zhang, Jue; Fang, Jing

    2016-07-01

    Molecular imaging techniques are becoming increasingly important in biomedical research and potentially in clinical practice. We present a continuous-terahertz (THz)-wave molecular imaging system for biomedical applications, in which an infrared (IR) laser is integrated into a 0.2-THz reflection-mode continuous-THz-wave imaging system to induce surface plasmon polaritons on the nanoparticles and further improve the intensity of the reflected signal from the water around the nanoparticles. A strong and rapid increment of the reflected THz signal in the nanoparticle solution upon the IR laser irradiation is demonstrated, using either gold or silver nanoparticles. This low-cost, simple, and stable continuous-THz-wave molecular imaging system is suitable for miniaturization and practical imaging applications; in particular, it shows great promise for cancer diagnosis and nanoparticle drug-delivery monitoring.

  16. Molecular imaging of HER2-positive breast cancer

    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....

  17. Tight binding description of the STM image of molecular chains

    OpenAIRE

    Calev, Yoel; Cohen, Hezy; Cuniberti, Gianaurelio; Nitzan, Abraham; Porath, Danny

    2004-01-01

    A tight binding model for scanning tunneling microscopy images of a molecule adsorbed on a metal surface is described. The model is similar in spirit to that used to analyze conduction along molecular wires connecting two metal leads and makes it possible to relate these two measurements and the information that may be gleaned from the corresponding results. In particular, the dependence of molecular conduction properties along and across a molecular chain on the chain length, intersite elect...

  18. 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.

  19. Functional and Molecular Image Guidance in Radiotherapy Treatment Planning Optimization

    OpenAIRE

    Das, Shiva K.; Ten Haken, Randall K.

    2011-01-01

    Functional and molecular imaging techniques are increasingly being developed and used to quantitatively map the spatial distribution of parameters such as metabolism, proliferation, hypoxia, perfusion and ventilation, among others, onto anatomically-imaged normal organs and tumor. In radiotherapy optimization, these imaging modalities offer the promise of increased dose sparing to high functioning subregions of normal organs or dose escalation to selected subregions of tumor, as well as the p...

  20. Molecular Imaging of Healing After Myocardial Infarction

    OpenAIRE

    Naresh, Nivedita K; Ben-Mordechai, Tamar; Leor, Jonathan; Epstein, Frederick H

    2011-01-01

    The progression from acute myocardial infarction (MI) to heart failure continues to be a major cause of morbidity and mortality. Potential new therapies for improved infarct healing such as stem cells, gene therapy, and tissue engineering are being investigated. Noninvasive imaging plays a central role in the evaluation of MI and infarct healing, both clinically and in preclinical research. Traditionally, imaging has been used to assess cardiac structure, function, perfusion, and viability. H...

  1. 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.

  2. Molecular imaging in neuroendocrine tumors : Molecular uptake mechanisms and clinical results

    NARCIS (Netherlands)

    Koopmans, Klaas P.; Neels, Oliver N.; Kema, Ido P.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.; Jager, Pieter L.

    2009-01-01

    Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-

  3. 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.

  4. Multifunctional hydroxyapatite nanoparticles for drug delivery and multimodal molecular imaging

    International Nuclear Information System (INIS)

    Hydroxyapatite (HAp) is the most important constituent of biological tissues such as bone and teeth and exhibits several characteristic features. HAp nanoparticles (NPs) are good host materials and can be functionalized with various kinds of dopants and substrates. By endowing HAp NPs with desired properties in order to render them suitable for biomedical applications including cellular imaging, non-invasive and quantitative visualisation of molecular process occurring at cellular and subcellular levels becomes possible. Depending on their functional properties, HAp based nanoprobes can be divided into three classes, i.e., luminescent HAp NPs (for both down conversion and up conversion luminescence), magnetic HAp NPs, and luminomagnetic HAp NPs. Luminomagnetic HAp NPs are particularly attractive in terms of bimodal imaging and even multimodal imaging by virtue of their luminescence and magnetism. Functionalized HAp NPs are potential candidates for targeted drug delivery applications. This review (with 166 references) spotlights the cellular imaging applications of three types of HAp NPs. Specific sections cover aspects of molecular imaging and the various imaging modes, a comparison of the common types of nanoprobes for bioimaging, synthetic methods for making the various kinds of HAp NPs, followed by overviews on fluorescent NPs for bioimaging (such as quantum dots, gold nanoclusters, lanthanide-doped or fluorophore-doped NPs), magnetic HAp NPs for use in magnetic resonance imaging (MRI), luminomagnetic HAp NPs for bimodal imaging, and sections on drug delivery as well as cellular imaging applications of HAp based nanoprobes (including targeted imaging). (author)

  5. Emerging applications of conjugated polymers in molecular imaging.

    Science.gov (United States)

    Li, Junwei; Liu, Jie; Wei, Chen-Wei; Liu, Bin; O'Donnell, Matthew; Gao, Xiaohu

    2013-10-28

    In recent years, conjugated polymers have attracted considerable attention from the imaging community as a new class of contrast agent due to their intriguing structural, chemical, and optical properties. Their size and emission wavelength tunability, brightness, photostability, and low toxicity have been demonstrated in a wide range of in vitro sensing and cellular imaging applications, and have just begun to show impact in in vivo settings. In this Perspective, we summarize recent advances in engineering conjugated polymers as imaging contrast agents, their emerging applications in molecular imaging (referred to as in vivo uses in this paper), as well as our perspectives on future research.

  6. New imaging strategies for monitoring molecular pharmacotherapy of GIST; Neue bildgebende Strategien zum Monitoring molekularer Pharmakotherapien bei GIST

    Energy Technology Data Exchange (ETDEWEB)

    Berger, F.; Reiser, M. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2008-09-15

    Prognosis and clinical management of patients with gastrointestinal stromal tumors (GIST) has changed significantly with the introduction of new molecular-targeted drugs such as imatinib. This development is accompanied by a need to re-evaluate the established imaging criteria used to assess treatment response. The frequently used response evaluation criteria in solid tumors (RECIST) are mainly based on one-dimensional tumor size and do not take into account functional changes in responding GISTs such as a decrease in CT density or in the number of intratumoral vessels. Positron emission tomography (PET) has been found to be highly sensitive in detecting early response and to have a predictive value in the long term response to imatinib treatment. Monitoring the course of the disease by PET is limited due to scanner availability and economic constraints. Modified CT response criteria using a combination of tumor density and tumor size are especially promising in early response assessment and have a good prognostic value. Further optimization of existing response criteria and evaluation of new candidate markers of treatment response, such as quantitative perfusion will be the key for optimized monitoring of targeted therapies in GIST. (orig.) [German] Prognose und klinisches Management von Patienten mit gastrointestinalem Stromatumor (GIST) haben sich nach Einfuehrung neuer molekularer Pharmakotherapien wie Imatinib dramatisch geaendert. Damit einhergegangen ist die Notwendigkeit, bisher etablierte bildgebende Methoden zur Beurteilung des Ansprechens auf die Therapie zu ueberdenken. Die derzeit am haeufigsten eingesetzten Responsekriterien, die RECIST- (Response-evaluation-criteria-in-solid-tumors-)Kriterien, beruhen wesentlich auf der unidirektionalen Messung tumoroeser Laesionen. Aenderungen in der CT-Dichte oder der Anzahl intratumoraler Blutgefaesse werden hierbei nicht beruecksichtigt. Die Positronenemissionstomographie (PET) ist ein sensitives Verfahren zur

  7. Molecular imaging in myeloma precursor disease

    OpenAIRE

    Mena, E.; Choyke, P; Tan, E; Landgren, O; Kurdziel, K

    2011-01-01

    Multiple myeloma (MM) is consistently preceded by its pre-malignant states, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). By definition, precursor conditions do not exhibit end-organ disease (anemia, hypercalcemia, renal failure, skeletal lytic lesions, or a combination of these). However, new imaging methods are demonstrating that some patients in the MGUS or SNM category are exhibiting early signs of MM.

  8. 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.

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

    Science.gov (United States)

    Alcantara, David; Pernia Leal, Manuel; Garcia, Irene; Garcia-Martin, Maria Luisa

    2014-12-01

    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.

  10. Molecular imaging with dynamic contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    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.

  11. 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.)

  12. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    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.)

  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. Molecular Imaging: A Promising Tool to Monitor Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2011-01-01

    Full Text Available Replacement of insulin production by pancreatic islet transplantation has great potential as a therapy for type 1 diabetes mellitus. At present, the lack of an effective approach to islet grafts assessment limits the success of this treatment. The development of molecular imaging techniques has the potential to fulfill the goal of real-time noninvasive monitoring of the functional status and viability of the islet grafts. We review the application of a variety of imaging modalities for detecting endogenous and transplanted beta-cell mass. The review also explores the various molecular imaging strategies for assessing islet delivery, the metabolic effects on the islet grafts as well as detection of immunorejection. Here, we highlight the use of combined imaging and therapeutic interventions in islet transplantation and the in vivo monitoring of stem cells differentiation into insulin-producing cells.

  15. Development of molecular imaging in the European radiological community

    International Nuclear Information System (INIS)

    The recent and concomitant advances in molecular biology and imaging for diagnosis and therapy will place in vivo imaging techniques at the centre of their clinical transfer. Before that, a wide range of multidisciplinary preclinical research is already taking place. The involvement of radiologists in this new field of imaging sciences is therefore absolutely mandatory during these two phases of development. Achievement of such objectives requires the refinement of strategy within the European radiological community and the European Society of Radiology (ESR) will have to drive a number of actions to stimulate the younger generation of radiologists and to facilitate their access to knowledge. For that purpose, a molecular imaging (MI) subcommittee of the ESR Research Committee based on a group of involved radiologists will be constituted to develop contacts with other constitutive committees and associated societies to provide proposals to our community. (orig.)

  16. Molecular imaging of vessels in mouse models of disease

    International Nuclear Information System (INIS)

    Vascular imaging of angiogenesis in mouse models of disease requires multi modal imaging hardware capable of targeting both structure and function at different physical scales. The three dimensional (3D) structure and function vascular information allows for accurate differentiation between biological processes. For example, image analysis of vessel development in angiogenesis vs. arteriogenesis enables more accurate detection of biological variation between subjects and more robust and reliable diagnosis of disease. In the recent years a number of micro imaging modalities have emerged in the field as preferred means for this purpose. They provide 3D volumetric data suitable for analysis, quantification, validation, and visualization of results in animal models. This review highlights the capabilities of microCT, ultrasound and microPET for multimodal imaging of angiogenesis and molecular vascular targets in a mouse model of tumor angiogenesis. The basic principles of the imaging modalities are described and experimental results are presented.

  17. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

    OpenAIRE

    Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P.; Sen, Chandan K.; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

    2009-01-01

    Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellula...

  18. 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.

  19. 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.

  20. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Science.gov (United States)

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    2014-01-01

    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. PMID:23536223

  1. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    International Nuclear Information System (INIS)

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [18F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

  2. 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

  3. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Bishnu P. [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Wang, Thomas D., E-mail: thomaswa@umich.edu [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2010-06-11

    Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.

  4. 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 m

  5. Multi-modality systems for molecular tomographic imaging

    Science.gov (United States)

    Li, Mingze; Bai, Jing

    2009-11-01

    In vivo small animal imaging is a cornerstone in the study of human diseases by providing important clues on the pathogenesis, progression and treatment of many disorders. Molecular tomographic imaging can probe complex biologic interactions dynamically and to study diseases and treatment responses over time in the same animal. Current imaging technique including microCT, microMRI, microPET, microSPECT, microUS, BLT and FMT has its own advantages and applications, however, none of them can provide structural, functional and molecular information in one context. Multi-modality imaging, which utilizes the strengths of different modalities to provide a complete understanding of the object under investigation, emerges as an important alternative in small animal imaging. This article is to introduce the latest development of multimodality systems for small animal tomographic imaging. After a systematic review of imaging principles, systems and commerical products for each stand-alone method, we introduce some multimodality strategies in the latest years. In particular, two dual-modality systems, i.e. FMT-CT and FMT-PET are presented in detail. The end of this article concludes that though most multimodality systems are still in a laboratory research stage, they will surely undergo deep development and wide application in the near future.

  6. 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.

  7. Low-Noise CMOS Image Sensors for Radio-Molecular Imaging

    NARCIS (Netherlands)

    Chen, Y.

    2012-01-01

    This thesis presents the development of low-noise CMOS image sensors for radio-molecular imaging. The development is described in two directions: firstly, from the technology point of view to reduce the pixel noise level, and secondly from the design point of view to reduce the pixel readout circuit

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

    International Nuclear Information System (INIS)

    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.)

  9. 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.)

  10. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Quong, J N

    2004-02-19

    The goal of this project is to develop experimental and computational protocols to use SIMS to image the chemical composition of biological samples, focusing on optimizing sample preparation protocols and developing multivariate data analysis methods. Our results on sample preparation, molecular imaging, and multivariate analysis have been presented at several meeting abstracts (UCRL151797ABS, UCRL151797ABSREV1, UCRL151426ABS, UCRL201277, UCRL154757). A refereed paper describing our results for sample preparation and molecular imaging of various endogenous biomolecules as well as the mutagen PhIP has been accepted for publication (UCRL-JC-151797). We are also preparing two additional papers describing our multivariate analysis methods to analyze spectral data. As these papers have not been submitted, their content is included in this final report.

  11. The Utility of Molecular Imaging in Prostate Cancer.

    Science.gov (United States)

    Leiblich, Aaron; Stevens, Daniel; Sooriakumaran, Prasanna

    2016-03-01

    Prostate cancer is the commonest solid-organ cancer diagnosed in males and represents an important source of morbidity and mortality worldwide. Imaging plays a crucial role in diagnosing prostate cancer and informs the ongoing management of the disease at all stages. Several novel molecular imaging technologies have been developed recently that have the potential to revolutionise disease diagnosis and the surveillance of patients living with prostate cancer. These innovations include hyperpolarised MRI, choline PET/CT and PSMA PET/CT. The major utility of choline and PSMA PET/CT currently lies in their sensitivity for detecting early recurrence after radical treatment for prostate cancer and identifying discrete lesions that may be amenable to salvage therapy. Molecular imaging is likely to play a future role in characterising genetic and biochemical signatures in individual tumours, which may be of particular significance as cancer therapies move into an era of precision medicine. PMID:26894753

  12. 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.)

  13. Molecular application of spectral photoacoustic imaging in pancreatic cancer pathology

    Science.gov (United States)

    Lakshman, Minalini; Hupple, Clinton; Lohse, Ines; Hedley, David; Needles, Andrew; Theodoropoulos, Catherine

    2012-12-01

    Spectral imaging is an advanced photo-acoustic (PA) mode that can discern optical absorption of contrast agent(s) in the tissue micro-environment. This advancement is made possible by precise control of optical wavelength using a tunable pulsed laser, ranging from 680-970 nm. Differential optical absorption of blood oxygenation states makes spectral imaging of hemoglobin ideal to investigate remodeling of the tumor microenvironment- a molecular change that renders resistance to standard cancer treatment. Approach: Photo-acoustic imaging was performed on the Vevo® LAZR system (VisualSonics) at 5-20 Hz. Deep abdominal imaging was accomplished with a LZ250D probe at a center frequency of 21MHz and an axial resolution of 75 μm. The tumor model was generated in an immune compromised mouse by surgical implantation of primary patient derived tumors, in the pancreas. Results: Spectral imaging for oxygen saturation at 750 nm and 850 nm characterized this tumor with a poorly oxygenated core surrounded by a well oxygenated periphery. Multispectral imaging identified a sub region in the core with a four-fold signal exclusively at 750 and 800 nm. A co-registered 2D image of this region was shown to be echogenic and calcification was suspected. Perfusion imaging with contrast enhanced ultrasound using microbubbles (Vevo MicroMarker® contrast agents, VisualSonics) identified functional vessels towards this sub region. Histology confirmed calcification and vascularization in the tumor core. Taken together, non-invasive characterization of the tumor microenvironment using photo-acoustics rendered spectral imaging a sensitive tool to monitor molecular changes representative of progression of pancreatic cancer that kills within 6 months of diagnosis.

  14. Imprints of Molecular Clouds in Radio Continuum Images

    CERN Document Server

    Yusef-Zadeh, F

    2012-01-01

    We show radio continuum images of several molecular complexes in the inner Galaxy and report the presence of dark features that coincide with dense molecular clouds. Unlike infrared dark clouds, these features which we call "radio dark clouds" are produced by a deficiency in radio continuum emission from molecular clouds that are embedded in a bath of UV radiation field or synchrotron emitting cosmic ray particles. The contribution of the continuum emission along different pathlengths results in dark features that trace embedded molecular clouds. The new technique of identifying cold clouds can place constraints on the depth and the magnetic field of molecular clouds when compared to those of the surrounding hot plasma radiating at radio wavelengths. The study of five molecular complexes in the inner Galaxy, Sgr A, Sgr B2, radio Arc, the snake filament and G359.75-0.13 demonstrate an anti--correlation between the distributions of radio continuum and molecular line and dust emission. Radio dark clouds are iden...

  15. Engineering imaging probes and molecular machines for nanomedicine.

    Science.gov (United States)

    Tong, Sheng; Cradick, Thomas J; Ma, Yan; Dai, Zhifei; Bao, Gang

    2012-10-01

    Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed.

  16. 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

  17. 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, with this achie...... small animal PET/CT for studies of muscle and tendon in exercise models. © 2011 Bentham Science Publishers Ltd.......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, with this...... 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...

  18. Ultrafast Molecular Imaging by Laser Induced Electron Diffraction

    CERN Document Server

    Peters, Michel; Cornaggia, Christian; Saugout, Sébastien; Charron, Eric; Keller, Arne; Atabek, Osman

    2010-01-01

    We address the feasibility of imaging geometric and orbital structure of a polyatomic molecule on an attosecond time-scale using the Laser Induced Electron Diffraction, LIED, technique [T. Zuo \\textit{et al.}, Chem. Phys. Lett. \\textbf{259}, 313 (1996)]. We present numerical results obtained for the CO$_2$ molecule using a single active electron model. The molecular geometry (bond-lengths) is determined within 3% of accuracy from a diffraction pattern which also reflects the nodal properties of the initial molecular orbital. Robustness of the structure determination is discussed with respect to vibrational and rotational motions with a complete interpretation of the laser-induced mechanisms.

  19. Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

    Science.gov (United States)

    Kujala, Naresh Gandhi

    Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The

  20. 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...... 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...

  1. Advances in radionuclide molecular imaging of pancreatic β-cells

    International Nuclear Information System (INIS)

    In both type 1 and type 2 diabetes mellitus, β-cell mass (BCM) is lost.Various treatments are developed to restore or reconstruct BCM. The development of non-invasive methods to quantify BCM in vivo offers the potential for early detection of β-cell dysfunction prior to the clinical onset of diabetes. PET imaging with radioligands that directly target the pancreatic β-cells appears promising. The ability to determine the BCM has been investigated in several targets and their corresponding radiotracers, including radiolabeled receptor ligands, antibodies, metabolites and reporter genes. Therefore, we summarize the recent progress in radionuclide molecular imaging of pancreatic β-cells. (authors)

  2. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

    Full Text Available Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs, biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  3. Tau PET: the next frontier in molecular imaging of dementia.

    Science.gov (United States)

    Xia, Chenjie; Dickerson, Bradford C

    2016-09-01

    We have arrived at an exciting juncture in dementia research: the second major pathological hallmark of Alzheimer's disease (AD)-tau-can now be seen for the first time in the living human brain. The major proteinopathies in AD include amyloid-β plaques and neurofibrillary tangles (NFTs) made of hyperphosphorylated paired helical filament (PHF) tau. Since its advent more than a decade ago, amyloid PET imaging has revolutionized the field of dementia research, enabling more confident diagnosis of the likely pathology in patients with a variety of clinical dementia syndromes, paving the way for the identification of people with preclinical or prodromal AD pathology, and serving as a minimally invasive molecular readout in clinical trials of putative disease-modifying interventions. Now that we are on the brink of a second revolution in molecular imaging in dementia, it is worth considering the likely potential impact of this development on the field. PMID:27334648

  4. 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

  5. Breast imaging technology: Probing physiology and molecular function using optical imaging - applications to breast cancer

    International Nuclear Information System (INIS)

    The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring

  6. PET-based molecular nuclear neuro-imaging

    International Nuclear Information System (INIS)

    Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

  7. Photoacoustic molecular imaging for in vivo liver iron quantitation

    Science.gov (United States)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  8. Mit der Kamera forschend auf Reisen

    OpenAIRE

    Mendel, Tommi

    2011-01-01

    Was haben Pilger- und Backpackerreisen gemeinsam? Inwiefern können beide als Übergangsrituale verstanden werden? Diese Fragen stellt sich Tommi Mendel in seiner Doktorarbeit und begleitete dafür Fusspilger und Globetrotter auf der Reise.

  9. 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.)

  10. Contributions on biomedical imaging, with a side-look at molecular imaging

    International Nuclear Information System (INIS)

    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.)

  11. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models.

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  12. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  13. Luminescent Nanomaterials for Molecular-Specific Cellular Imaging

    Science.gov (United States)

    Zvyagin, Andrei Vasilyevich; Song, Zhen; Nadort, Annemarie; Sreenivasan, Varun Kumaraswamy Annayya; Deyev, Sergey Mikhailovich

    Imaging of molecular trafficking in cells and biological tissue aided by molecular-specific fluorescent labeling is very attractive, since it affords capturing the key processes in comprehensive biological context. Several shortcomings of the existing organic dye labeling technology, however, call for development of alternative molecular reporters, with improved photostability, reduced cytotoxicity, and an increased number of controllable surface moieties. Such alternative molecular reporters are represented by inorganic luminescent nanoparticles (NP) whose optical, physical, and chemical properties are discussed on the examples of luminescent nanodiamonds (LND) and upconversion nanoparticles (UCNP). The emission origins of these nanomaterials differ markedly. LND emission results from individual nitrogen-vacancy color-centers in a biocompatible nanodiamond host whose properties can be controlled via size and surface groups. Photophysics of UCNP is governed by the collective, nonlinear excitation transfer processes, resulting in conversion of longer-wavelength excitation to the shorter-wavelength emission. The emission/excitation spectral properties of UCNP falling within the biological tissue transparency window open new opportunities of almost complete suppression of the cell/tissue autofluorescence background. The developed surface of these nanoparticles represents a flexible platform populated with biocompatible surface moieties onto which cargo and targeting biomolecules can be firmly docked through a process called bioconjugation. These bioconjugated modules, e.g., nanodiamond-antibody, (quantum dot)-somatostatin, or (upconversion nanoparticle)-(mini-antibody) can gain admission into the cells by initiating the cell-specific, cell-recognized communication protocol. In this chapter, we aim to demonstrate the whole bottom-up bio-nano-optics approach for optical biological imaging capturing luminescent nanoparticle design, surface activation, and bioconjugation

  14. 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.

  15. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Science.gov (United States)

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

    2015-08-01

    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.

  16. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    OpenAIRE

    Lu, Feng-Mei; Yuan, Zhen

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in n...

  17. 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

  18. 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...

  19. Laser induced - tunneling, electron diffraction and molecular orbital imaging

    International Nuclear Information System (INIS)

    Full text: Multiphoton ionization in the tunneling limit is similar to tunneling in a scanning tunneling microscope. In both cases an electron wave packet tunnels from a bound (or valence) state to the continuum. I will show that multiphoton ionization provides a route to extend tunneling spectroscopy to the interior of transparent solids. Rotating the laser polarization is the analogue of scanning the STM tip - a means of measuring the crystal symmetry of a solid. In gas phase molecules the momentum spectrum of individual electrons can be measured. I will show that, as we rotate the molecule with respect to the laser polarization, the photoelectron spectrum samples a filter projection of the momentum wave function (the molecular analogue to the band structure) of the ionizing orbital. Some electrons created during multiphoton ionization re-collide with their parent ion. I will show that they diffract, revealing the scattering potential of the ion - the molecular structure. The electron can also interfere with the initial orbital from which it separated, creating attosecond XUV pulses or pulse trains. The amplitude and phase of the radiation contains all information needed to re-construct the image of the orbital (just as a sheared optical interferometer can fully characterize an optical pulse). Strong field methods provide an extensive range of new tools to apply to atomic, molecular and solid-state problems. (author)

  20. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.

    Science.gov (United States)

    Scherer, Daniel J; Psaltis, Peter J

    2016-08-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093

  1. A Review of Tumor Specific Imaging Methods: A Glance at the Use of Molecular Imaging

    Directory of Open Access Journals (Sweden)

    M.A. Oghabian

    2005-08-01

    Full Text Available Introduction & Background: Conventional imaging modalities of CT, MRI, ultrasound, radionuclide, and even metabolic PET are insensitive to reveal tumor and metastasis of less than few millimeters containing not much fewer than 500,000 cells. At this size, a tu-mor has effectively undergone about 20 cell dou-blings, and is sufficiently stuffed with gene defects and likely to metastasize. New techniques generally known as molecular imaging lead to a patient-specific approach based on physiologic, antigenic, molecular, and genetic disease markers. In this article, Current and the near term trends and techniques in early de-tection of cancer using gene specific, cell specific, or even patient specific approaches are summarized. A number of markers are used for cancer imaging. Anatomic markers show cell morphology defects at the sub-10-µm level on CT, MRI, and OCT (Optical Coherence Tomography. These techniques often fail to provide accurate and basic information necessary to manage the patient’s disease such as true metastatic extent. Functional markers use dynamic features, such as capillary leak (using ICG, IndoCyanine Green, lymphatic transport (by colloid, or Tc-Sestamibi, blood oxygenation, and blood flow. The features provide signal by a bulk phenomenon, and hence are still insensitive. More specifically, anti-genic probes, such as targeted antibodies have been demonstrated effectively in vivo for both diagnostic and therapeutic purposes, such as PSMA in the pros-tate cancer, CEA in colorectal cancer, and HER-2/neu in breast cancer. Metabolic probes accumulate at the site of a specific metabolic activity, and rely on imag-ing agents involving certain enzymatic pathways or transport functions of the cell. Examples are 18FDG (18F-fluoroDeoxyGlucose in PET and 11C-thymidine. Recent spectroscopy techniques do not need such labeled probes. The common method for in-vivo spectroscopy is MRSI (Proton Magnetic Resonance Spectroscopy that can

  2. Der westliche Blick auf den Orient

    Directory of Open Access Journals (Sweden)

    Antje Schrupp

    2007-11-01

    Full Text Available Angesichts der aktuellen Debatten über den Islam zeigen Christina von Braun und Bettina Mathes die viele Jahrhunderte alte Interpretationsgeschichte des Orients aus westlicher Perspektive auf. In ihrem materialreichen Band schildern sie die historische und geografische Vielfalt des Phänomens „Islam“ und zeigen, wie westliches Selbstverständnis und Projektionen das Bild des Okzidents vom Orient seit langem und bis heute prägen – auch da, wo man es auf den ersten Blick nicht vermuten würde.

  3. Untersuchungen einer Kraftmesstechnik basierend auf optischer Objektverfolgung

    OpenAIRE

    Rutschmann, Sabrina; Martinez Schramm, Jan; Wolfram, Jeremy; Laurence, Stuart

    2009-01-01

    Im Hochenthalpiekanal Göttingen (HEG) des Deutschen Zentrums für Luft- und Raumfahrt (DLR) soll im Rahmen des ExoMars-Projektes erstmalig eine berührungslose Kraftmesstechnik einge-setzt werden. Eine Hochgeschwindigkeitskamera nimmt die Bewegungstrajektorie eines freiflie-genden Modells auf, aus der mit einer computergestützten Objektdetektion auf die angreifen-den Kräfte rückgeschlossen werden soll. Ziel der hier beschriebenen Arbeit soll es sein, die Genauigkeit und damit die Anwendbark...

  4. [Molecular imaging for early diagnosis of Alzheimer's disease].

    Science.gov (United States)

    Pozo García, Miguel Angel

    2004-01-01

    The progressive aging of the population and the difficulty of diagnosing and treating Alzheimer's disease (AD) portends an exponencial increase in the prevalence of this illness. One way to approach this social and health problem is to develop diagnostic techniques that allow us to detect the disease in its pre-clinical stages and apply early treatment that can slow down AD advance. Molecular imaging, in particular that generated by positron emission tomography with 2-fluoro-2 deoxi-D-glucose (PET-FDG) has shown high sensitivity in detecting changes in cerebral metabolic activity in the early stages of AD, and allow other dementias and physiological changes that accompany normal aging to be distinguished from AD. PMID:15997594

  5. Molecular Imaging of Ultrathin Pentacene Films: Evidence for Homoepitaxy

    Science.gov (United States)

    Wu, Yanfei; Haugstad, Greg; Frisbie, C. Daniel

    2013-03-01

    Ultrathin polycrystalline films of organic semiconductors have received intensive investigations due to the critical role they play in governing the performance of organic thin film transistors. In this work, a variety of scanning probe microscopy (SPM) techniques have been employed to investigate ultrathin polycrystalline films (1-3 nm) of the benchmark organic semiconductor pentacene. By using spatially resolved Friction Force Microscopy (FFM), Kelvin Probe Force Microscopy (KFM) and Electrostatic Force Microscopy (EFM), an interesting multi-domain structure is revealed within the second layer of the films, characterized as two distinct friction and surface potential domains correlating with each other. The existence of multiple homoepitaxial modes within the films is thus proposed and examined. By employing lattice-revolved imaging using contact mode SPM, direct molecular evidence for the unusual homoepitaxy is obtained.

  6. Recent trends in Molecular Imaging : PET/CT in Neurology

    Directory of Open Access Journals (Sweden)

    R P Tripathi

    2015-06-01

    Full Text Available PET/CT is an important molecular imaging technique for the assessment ofneurological disorders. The most widely used radiopharmaceutical for both clinical and research purposes is [18F] 2-fluoro-2-deoxy-D-glucose (FDG. It is extensively used owing to its favourable physical characteristics. It enables depiction of cerebral glucose metabolism, and has thus been used to study various pathological states. Despite this, FDG has its own limitations. This is owing to its limited specificity and high cortical uptake. This has paved the way for the development of several non-FDG PET radiopharmaceuticals. We present the insights gained at our institution, using these radiotracers in the assessment of neurological disease. Our study shows that the use of FDG and non-FDG novel PET radiopharmaceuticals facilitates the early diagnosis, delineation of extent, prognostication and monitoring of therapeutic response in several neuropathological states.PET/CT is an important molecular imaging technique for the assessment ofneurological disorders. The most widely used radiopharmaceutical for both clinicaland research purposes is [18F] 2-fluoro-2-deoxy-D-glucose (FDG. It is extensivelyused owing to its favourable physical characteristics. It enables depiction of cerebralglucose metabolism, and has thus been used to study various pathological states.Despite this, FDG has its own limitations. This is owing to its limited specificity andhigh cortical uptake. This has paved the way for the development of several non-FDGPET radiopharmaceuticals. We present the insights gained at our institution, usingthese radiotracers in the assessment of neurological disease. Our study shows that theuse of FDG and non-FDG novel PET radiopharmaceuticals facilitates the earlydiagnosis, delineation of extent, prognostication and monitoring of therapeuticresponse in several neuropathological states.

  7. 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.

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

    International Nuclear Information System (INIS)

    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

  9. Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rajagopalan, Raghavan

    2006-01-30

    The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling study revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.

  10. New Researches and Application Progress of Commonly Used Optical Molecular Imaging Technology

    Directory of Open Access Journals (Sweden)

    Zhi-Yi Chen

    2014-01-01

    Full Text Available Optical molecular imaging, a new medical imaging technique, is developed based on genomics, proteomics and modern optical imaging technique, characterized by non-invasiveness, non-radiativity, high cost-effectiveness, high resolution, high sensitivity and simple operation in comparison with conventional imaging modalities. Currently, it has become one of the most widely used molecular imaging techniques and has been applied in gene expression regulation and activity detection, biological development and cytological detection, drug research and development, pathogenesis research, pharmaceutical effect evaluation and therapeutic effect evaluation, and so forth, This paper will review the latest researches and application progresses of commonly used optical molecular imaging techniques such as bioluminescence imaging and fluorescence molecular imaging.

  11. 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)

  12. Value based management auf Basis von ERIC

    OpenAIRE

    Velthuis, Louis John

    2004-01-01

    Im Rahmen des Value Based Managements sollen alle Manahmen der Unternehmensfhrung auf die Steigerung des intrinsischen Marktwertes des Eigenkapitals ausgerichtet werden. Hauptanwendungsbereiche des Value Based Managements sind die Planung, Performancemessung, Managemententlohnung sowie die Bereichssteuerung. Eine konsequente shareholder-orientierte Steuerung beinhaltet eine adquate Ermittlung von Wertbeitrgen in den einzelnen Anwendungsbereichen. Hierzu dienen insbesondere absolute Wertbeitra...

  13. Dünne Beschichtungen auf Biomaterialien

    Science.gov (United States)

    Klee, Doris; Lahann, Jörg; Plüster, Wilhelm

    Ein Schwerpunkt der Implantatentwicklung liegt in der Synthese und Verarbeitung geeigneter Biomaterialien, die bezüglich ihrer mechanischen Eigenschaften und ihrer Stabilität die erwünschte Funktion im Organismus erfüllen sollen. Die biologische Antwort auf Biomaterialien im Implantateinsatz wird jedoch hauptsächlich von der chemischen Zusammensetzung und der Struktur der Implantatoberfläche bestimmt [1]. Sie ist entscheidend für die Langzeitverträglichkeit eines Implantats. Geeignete Ansätze zur Verbesserung der Grenzflächenverträglichkeit von Biomaterialien, ohne die mechanischen Eigenschaften und die Funktionalität des Implantates zu verändern, beruhen auf die Aufbringung einer definierten, falls erforderlich biologisch aktiven Beschichtung auf die Werkstoffoberfläche. Bei den eingesetzten Beschichtungsverfahren handelt es sich vielfach um bekannte Verfahren zur Oberflächenmodifizierung technischer Werkstoffe, die auf physikalischen und chemischen Prozessen basieren. Je nach Beschichtungsverfahren können unterschiedliche Schichtdicken erzielt werden. Zur Charakterisierung der Zusammensetzung und Struktur der beschichteten Biomaterialoberflächen ist der Einsatz oberflächensensitiver Analytik unverzichtbar. Vielfach wird eine Kombination von Methoden eingesetzt, die sich hinsichtlich ihrer Informationstiefe und Informationsaussage unterscheiden [1].

  14. Regionale Einflussfaktoren auf den Ausbau erneuerbarer Energien

    OpenAIRE

    Keppler, Dorothee

    2007-01-01

    First published in GAIA: Keppler, Dorothee: Regionale Einflussfaktoren auf den Ausbau erneuerbarer Energien : Ergebnisse einer Fallstudie in der Brandenburger Energieregion Lausitz. - In: GAIA : ökologische Perspektiven für Wissenschaft und Gesellschaft. - ISSN: 0940-5550. - 16 (2007), 4, pp. 289–296.

  15. Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2015-07-01

    Full Text Available Magnetic resonance imaging (MRI of glioblastoma multiforme (GBM with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA3 agent, a scrambled-Tris-(Gd-DOTA3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA3 agent over time compared to the non-specific contrast agent currently in clinical use.

  16. Multispectral optoacoustic and MRI coregistration for molecular imaging of orthotopic model of human glioblastoma.

    Science.gov (United States)

    Attia, Amalina Binte Ebrahim; Ho, Chris Jun Hui; Chandrasekharan, Prashant; Balasundaram, Ghayathri; Tay, Hui Chien; Burton, Neal C; Chuang, Kai-Hsiang; Ntziachristos, Vasilis; Olivo, Malini

    2016-07-01

    Multi-modality imaging methods are of great importance in oncologic studies for acquiring complementary information, enhancing the efficacy in tumor detection and characterization. We hereby demonstrate a hybrid non-invasive in vivo imaging approach of utilizing magnetic resonance imaging (MRI) and Multispectral Optoacoustic Tomography (MSOT) for molecular imaging of glucose uptake in an orthotopic glioblastoma in mouse. The molecular and functional information from MSOT can be overlaid on MRI anatomy via image coregistration to provide insights into probe uptake in the brain, which is verified by ex vivo fluorescence imaging and histological validation. In vivo MSOT and MRI imaging of an orthotopic glioma mouse model injected with IRDye800-2DG. Image coregistration between MSOT and MRI enables multifaceted (anatomical, functional, molecular) information from MSOT to be overlaid on MRI anatomy images to derive tumor physiological parameters such as perfusion, haemoglobin and oxygenation. PMID:27091626

  17. A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK.

    Science.gov (United States)

    Fawal, Mohamad; Armstrong, Florence; Ollier, Severine; Dupont, Henri; Touriol, Christian; Monsarrat, Bernard; Delsol, Georges; Payrastre, Bernard; Morello, Dominique

    2006-10-15

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a chimeric protein expressed in a subset of cases of anaplastic large cell lymphoma (ALCL) for which constitutive expression represents a key oncogenic event. The ALK signaling pathway is complex and probably involves functional redundancy between various signaling substrates of ALK. Despite numerous studies on signaling mediators, the molecular mechanisms contributing to the distinct oncogenic features of NPM-ALK remain incompletely understood. The search for additional interacting partners of NPM-ALK led to the discovery of AUF1/hnRNPD, a protein implicated in AU-rich element (ARE)-directed mRNA decay. AUF1 was immunoprecipitated with ALK both in ALCL-derived cells and in NIH3T3 cells stably expressing NPM-ALK or other X-ALK fusion proteins. AUF1 and NPM-ALK were found concentrated in the same cytoplasmic foci, whose formation required NPM-ALK tyrosine kinase activity. AUF1 was phosphorylated by ALK in vitro and was hyperphosphorylated in NPM-ALK-expressing cells. Its hyperphosphorylation was correlated with increased stability of several AUF1 target mRNAs encoding key regulators of cell proliferation and with increased cell survival after transcriptional arrest. Thus, AUF1 could function in a novel pathway mediating the oncogenic effects of NPM-ALK. Our data establish an important link between oncogenic kinases and mRNA turnover, which could constitute a critical aspect of tumorigenesis.

  18. Exploiting Molecular Biology by Time-Resolved Fluorescence Imaging

    Science.gov (United States)

    Müller, Francis; Fattinger, Christof

    Many contemporary biological investigations rely on highly sensitive in vitro assays for the analysis of specific molecules in biological specimens, and the main part of these assays depends on high-sensitivity fluorescence detection techniques for the final readout. The analyzed molecules and molecular interactions in the specimen need to be detected in the presence of other highly abundant biomolecules, while the analyzed molecules themselves are only present at nano-, pico-, or even femtomolar concentration.A short scientific rationale of fluorescence is presented. It emphasizes the use of fluorescent labels for sensitive assays in life sciences and specifies the main properties of an ideal fluorophore. With fluorescence lifetimes in the microsecond range and fluorescence quantum yield of 0.4 some water soluble complexes of Ruthenium like modified Ru(sulfobathophenanthroline) complexes fulfill these properties. They are outstanding fluorescent labels for ultrasensitive assays as illustrated in two examples, in drug discovery and in point of care testing.We discuss the fundamentals and the state-of-the-art of the most sensitive time-gated fluorescence assays. We reflect on how the imaging devices currently employed for readout of these assays might evolve in the future. Many contemporary biological investigations rely on highly sensitive in vitro assays for the analysis of specific molecules in biological specimens, and the main part of these assays depends on high-sensitivity fluorescence detection techniques for the final readout. The analyzed molecules and molecular interactions in the specimen need to be detected in the presence of other highly abundant biomolecules, while the analyzed molecules themselves are only present at nano-, pico-, or even femtomolar concentration.A short scientific rationale of fluorescence is presented. It emphasizes the use of fluorescent labels for sensitive assays in life sciences and specifies the main properties of an ideal

  19. Translational applications of molecular imaging in cardiovascular disease and stem cell therapy.

    Science.gov (United States)

    Du, Wei; Tao, Hongyan; Zhao, Shihua; He, Zuo-Xiang; Li, Zongjin

    2015-09-01

    Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Molecular imaging techniques provide valuable information at cellular and molecular level, as opposed to anatomical and structural layers acquired from traditional imaging modalities. More specifically, molecular imaging employs imaging probes which interact with specific molecular targets and therefore makes it possible to visualize biological processes in vivo. Molecular imaging technology is now progressing towards preclinical and clinical application that gives an integral and comprehensive guidance for the investigation of cardiovascular disease. In addition, cardiac stem cell therapy holds great promise for clinical translation. Undoubtedly, combining stem cell therapy with molecular imaging technology will bring a broad prospect for the study and treatment of cardiac disease. This review will focus on the progresses of molecular imaging strategies in cardiovascular disease and cardiac stem cell therapy. Furthermore, the perspective on the future role of molecular imaging in clinical translation and potential strategies in defining safety and efficacy of cardiac stem cell therapies will be discussed.

  20. Perspectives in molecular imaging through translational research, human medicine, and veterinary medicine.

    Science.gov (United States)

    Berry, Clifford R; Garg, Predeep

    2014-01-01

    The concept of molecular imaging has taken off over the past 15 years to the point of the renaming of the Society of Nuclear Medicine (Society of Nuclear Medicine and Molecular Imaging) and Journals (European Journal of Nuclear Medicine and Molecular Imaging) and offering of medical fellowships specific to this area of study. Molecular imaging has always been at the core of functional imaging related to nuclear medicine. Even before the phrase molecular imaging came into vogue, radionuclides and radiopharmaceuticals were developed that targeted select physiological processes, proteins, receptor analogs, antibody-antigen interactions, metabolites and specific metabolic pathways. In addition, with the advent of genomic imaging, targeted genomic therapy, and theranostics, a number of novel radiopharmaceuticals for the detection and therapy of specific tumor types based on unique biological and cellular properties of the tumor itself have been realized. However, molecular imaging and therapeutics as well as the concept of theranostics are yet to be fully realized. The purpose of this review article is to present an overview of the translational approaches to targeted molecular imaging with application to some naturally occurring animal models of human disease.

  1. A Molecular Imaging Approach to Mercury Sensing Based on Hyperpolarized (129)Xe Molecular Clamp Probe.

    Science.gov (United States)

    Guo, Qianni; Zeng, Qingbin; Jiang, Weiping; Zhang, Xiaoxiao; Luo, Qing; Zhang, Xu; Bouchard, Louis-S; Liu, Maili; Zhou, Xin

    2016-03-14

    Mercury pollution, in the form of mercury ions (Hg(2+)), is a major health and environmental hazard. Commonly used sensors are invasive and limited to point measurements. Fluorescence-based sensors do not provide depth resolution needed to image spatial distributions. Herein we report a novel sensor capable of yielding spatial distributions by MRI using hyperpolarized (129)Xe. A molecular clamp probe was developed consisting of dipyrrolylquinoxaline (DPQ) derivatives and twocryptophane-A cages. The DPQ derivatives act as cation receptors whereas cryptophane-A acts as a suitable host molecule for xenon. When the DPQ moiety interacts with mercury ions, the molecular clamp closes on the ion. Due to overlap of the electron clouds of the two cryptophane-A cages, the shielding effect on the encapsulated Xe becomes important. This leads to an upfield change of the chemical shift of the encapsulated Xe. This sensor exhibits good selectivity and sensitivity toward the mercury ion. This mercury-activated hyperpolarized (129)Xe-based chemosensor is a new concept method for monitoring Hg(2+) ion distributions by MRI.

  2. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    International Nuclear Information System (INIS)

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

  3. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  4. Basic research and clinical application of optical molecular imaging in breast cancer

    International Nuclear Information System (INIS)

    As a rapidly developing biomedical imaging technology,in vivo optical molecular imaging has been widely applied in various research fields owing to its unique real-time, quantitative and noninvasive characteristics. The applications of in vivo optical imaging technology in the basic and clinical research of breast cancer were reviewed, including detection of distant metastasis,tumor apoptosis, cell cycle, hypoxia and angiogenesis, ER-mediated molecular pathway, breast cancer stem cells, early diagnosis, sentinel node biopsy, evaluation of drug efficacy and detection of human epidermal growth factor receptor-2 (HER-2) expression. They all seem to have a promising potential in in vivo optical molecular imaging. (authors)

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

    Science.gov (United States)

    Knudsen, Gitte M; Jensen, Peter S; Erritzoe, David; Baaré, William F C; Ettrup, Anders; Fisher, Patrick M; Gillings, Nic; Hansen, Hanne D; Hansen, Lars Kai; Hasselbalch, Steen G; Henningsson, Susanne; Herth, Matthias M; Holst, Klaus K; Iversen, Pernille; Kessing, Lars V; Macoveanu, Julian; Madsen, Kathrine Skak; Mortensen, Erik L; Nielsen, Finn Årup; Paulson, Olaf B; Siebner, Hartwig R; Stenbæk, Dea S; Svarer, Claus; Jernigan, Terry L; Strother, Stephen C; Frokjaer, Vibe G

    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 related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank 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. PMID:25891375

  6. 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....

  7. Advance in molecular imaging research of vascular smooth muscle cells in the vascular diseases

    International Nuclear Information System (INIS)

    Vascular smooth muscle cells (VSMCs) are the primary cells within the vascular wall structure and maintain the tension of blood vessels, playing a key role in the restenosis, atherosclerosis and some other vascular diseases. With the development of molecular imaging, VSMCs cellular level of imaging studies is becoming more and more attention. The phenotype modulation, proliferation, migration and molecular imaging research progress of VSMCs in pathologic state were reviewed, to improve the management of vascular restenosis and atherosclerosis. (authors)

  8. 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...

  9. Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.

    Directory of Open Access Journals (Sweden)

    Markus Heine

    Full Text Available Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.

  10. 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.

  11. Informationssystem Versorgungsdaten bei DIMDI nimmt Pilotbetrieb auf

    OpenAIRE

    Müller, W.

    2014-01-01

    Am 17. Februar 2014 nimmt das neue Informationssystem Versorgungsdaten (Datentransparenz) des DIMDI den Pilotbetrieb auf. Damit werden erstmals aggregierte Versorgungsdaten der gesetzlichen Krankenkassen für Analysen nutzbar. Das System eröffnet insbesondere der Versorgungsforschung neue Möglichkeiten: Zugänglich werden unter anderem ambulante und stationäre Diagnosen sowie Daten über ambulant verordnete und abgerechnete Arzneimittel. In dieser Vollständigkeit - über die verschiedenen gesetzl...

  12. Recht auf Fortpflanzung und medizinischer Fortschritt

    OpenAIRE

    Knoop, Susanne

    2005-01-01

    Die Dissertation untersucht die Frage, ob es ein vom deutschen Grundgesetz geschuetztes Recht des Menschen auf Fortpflanzung gibt und welchen Umfang dieser Schutz ggf. hat. Dabei wird insbesondere geprueft, ob auch die Inanspruchnahme von Methoden der medizinisch assistierten Fortpflanzung Grundrechtsschutz geniesst. Zum Einstieg in das Thema wird im Teil 1 zunaechst eine Bestimmung der zur Fortpflanzung gehoerenden Entscheidungen und Taetigkeiten durchgefuehrt, verbunden mit einer begri...

  13. Finanzmarkt: Regulierung auf dem richtigen Weg?

    OpenAIRE

    Dullien, Sebastian; Paul, Stephan; Conrad, Christian A.; Otte, Max

    2012-01-01

    Fünf Jahre nach dem Ausbruch der Finanzmarktkrise hat sich einiges getan: Die USA und die Mitgliedstaaten der Europäischen Union haben verschiedene Regulierungen auf den Weg gebracht. Die Autoren beurteilen dies allerdings unterschiedlich. Zum einen seien die Regulierungen nicht ausreichend und nicht zielgenau, zum anderen sind Unklarheiten und eine Vermengung von Kompetenzen entstanden. Zudem stellt sich die Frage, ob eine striktere Finanzmarktregulierung den Kern des Problems trifft. Imm...

  14. 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 ...

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

    International Nuclear Information System (INIS)

    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 (20–140 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 are one of the first to present data from multi-energy photon-processing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at http://hdl.handle.net/10092/8531

  16. 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

  17. Small animal optoacoustic tomography system for molecular imaging of contrast agents

    Science.gov (United States)

    Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (bioluminescence based modalities for molecular imaging in live mice.

  18. Development of Optical Molecular Imaging System for the Acquisition of Bioluminescence Signals from Small Animals

    International Nuclear Information System (INIS)

    Optical imaging is providing great advance and improvement in genetic and molecular imaging of animals and humans. Optical imaging system consists of optical imaging devices, which carry out major function for monitoring, tracing, and imaging in most of molecular in-vivo researches. In bio-luminescent imaging, small animals containing luciferase gene locally irradiate light, and emitted photons transmitted through skin of the small animals are imaged by using a high sensitive charged coupled device (CCD) camera. In this paper, we introduced optical imaging system for the image acquisition of bio-luminescent signals emitted from small animals. In the system, Nikon lens and four LED light sources were mounted at the inside of a dark box. A cooled CCD camera equipped with a control module was used. We tested the performance of the optical imaging system using effendorf tube and light emitting bacteria which injected intravenously into CT26 tumor bearing nude mouse. The performance of implemented optical imaging system for bio-luminescence imaging was demonstrated and the feasibility of the system in small animal imaging application was proved. We anticipate this system could be a useful tool for the molecular imaging of small animals adaptable for various experimental conditions in future

  19. From molecular imaging to personalized radionuclide therapy of cancer

    International Nuclear Information System (INIS)

    Full text of publication follows. 68Gallium is a positron emitter (t1/2 68 min) which can be produced from a generator in a convenient, 'in-house' preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7700 68Ga PET/CT studies in patients with neuroendocrine tumors (NET) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, re-staging, therapy response evaluation and detection of unknown primary NET). The same peptides can be labeled with 177Lutetium or 90Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 mo) whereas NET of small bowel had a median PFS of 51 months. Side effects like 3-4 NEThro- or hemato-toxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRNT) results in excellent therapeutic responses. By

  20. 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

    2016-01-01

    Purpose 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. Procedures 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. Results 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. Conclusions 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. PMID:25905474

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

    Directory of Open Access Journals (Sweden)

    Qingqing Meng

    2013-01-01

    Full Text Available 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.

  2. 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.

  3. 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...

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

    NARCIS (Netherlands)

    B.P. de Kwaasteniet

    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 conne

  5. Gold nanoflowers for 3D volumetric molecular imaging of tumors by photoacoustic tomography

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Jiang[1,4; Zijian Deng[2,4; Dan Yang[3; Xin Deng[1; Qi Li[1; Yinlin Sha[3; Changhui Li[2; Dongsheng Xu[1

    2015-01-01

    By binding molecular probes that target tumor cells, gold nanoparticles (AuNPs) with superior characteristics have shown great potential in tumor molecular imaging studies. The non-invasive, high-resolution, and three-dimensional imaging of the targeted AuNPs within the tumor is desirable for both diagnosis and therapy. In this study, gold nanoflowers (AuNFs) are presented as a novel contrast agent for photoacoustic tomography (PAT). By binding to folic acid, the molecular probe, the tail-vein injected AuNFs concentrated within the tumor site in mice; this was clearly visualized by three-dimensional (3D) PAT imaging. In addition, toxicity assay proved that AuNFs were harmless to living cells and animals. Our results demonstrate that AuNFs have great potential in tumor molecular imaging.

  6. Molecular imaging of cancer: MR spectroscopy and beyond

    International Nuclear Information System (INIS)

    Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.

  7. Optical molecular imaging for detection of Barrett's-associated neoplasia

    Institute of Scientific and Technical Information of China (English)

    Nadhi Thekkek; Sharmila Anandasabapathy; Rebecca Richards-Kortum

    2011-01-01

    Recent advancements in the endoscopic imaging of Barrett's esophagus can be used to probe a wide range of optical properties that are altered with neoplastic progression.This review summarizes relevant changes in optical properties as well as imaging approaches that measures those changes.Wide-field imaging approaches include narrow-band imaging that measures changes in light scattering and absorption,and autofluorescence imaging that measure changes in endogenous fluorophores.High-resolution imaging approaches include optical coherence tomography,endocytoscopy,confocal microendoscopy,and high-resolution microendoscopy.These technologies,some coupled with an appropriate contrast agent,can measure differences in glandular morphology,nuclear morphology,or vascular alterations associated with neoplasia.Advances in targeted contrast agents are further discussed.Studies that have explored these technologies are highlighted;as are the advantages and limitations of each.

  8. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    OpenAIRE

    Bowsher, James; Yan, Susu; Roper, Justin; Giles, William; Yin, Fang-Fang

    2013-01-01

    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 S...

  9. Auswirkungen auf limnische Lebensräume

    OpenAIRE

    Haase, Peter; Hering, Daniel; Hoffmann, Andreas; Müller, Ruth; Nowak, Carsten; Pauls, Steffen; Stoll, Stefan; Straile, Dietmar

    2012-01-01

    Die direkten Auswirkungen der in Folge des projizierten Klimawandels steigenden Lufttemperaturen und veränderten Niederschläge auf limnischeSysteme in Deutschland sind vielfältig: So wird die veränderte Niederschlagssituation (mehr Extremereignisse, weniger Sommerniederschlag, mehr Winterniederschlag; s. Kap 2) das Abflussverhalten von Fließgewässern sowie die Wasserstände von Standgewässern in Form einer erhöhten Amplitude deutlich beeinflussen. Tendenziell werden kleinere Gewässer häufiger ...

  10. Zum gotischen gen. pl. auf

    Directory of Open Access Journals (Sweden)

    M. Grošelj

    1964-12-01

    Full Text Available Bekanntlich ist die got. Endung -ē eine Besonderheit, der in den übrigen germ. Sprachen nichts Vergleichbares gegenübersteht. Man nimmt wohl -allgemein an, dass es sich um eine innergot. Neuschöpfung handelt; auch ist eine idg. Endung des Gen. Pl. -ēm; linbelegt. Folgender Erklärungsversuch geht von der Annahme aus, dass die Triebkraft für dfese Neuschöpfupg in der Neigung zur Differenzierung des Maskulinums vom Femininum auf -ō (gibō : dagē zu suchen ist. Diese Neigung ist besonders im Nom. und Gen. bemerkbar.

  11. Macht auf das Tor! - Opens the gate!

    Directory of Open Access Journals (Sweden)

    Claudemir de Quadros

    2011-09-01

    Full Text Available Macht auf das Tor! (Abra o portão foi publicado, possivelmente, na primeira metade do século 20. Editado por Max Dirkschneider, Raimund Heuler e Felix Oberborbeck, apresenta músicas, rimas, piadas, jogos e canções.A edição apresentada nesse espaço é de um livro que pertence à família de Carolina Drebes, estudante do curso de Pedagogia do Centro Universitário Franciscano, Santa Maria/RS.

  12. Molecular shape of Lumbricus terrestris erythrocruorin studied by electron microscopy and image analysis

    NARCIS (Netherlands)

    Boekema, Egbert J.; Heel, Marin van

    1989-01-01

    The molecular structure of erythrocruorin (hemoglobin) from Lumbricus terrestris has been studied by electron microscopy of negatively stained particles. Over 1000 molecular projections were selected from a number of electron micrographs and were then classified by multivariate statistical image-pro

  13. 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...

  14. Imaging of Flow Patterns with Fluorescent Molecular Rotors

    OpenAIRE

    Mustafic, Adnan; Huang, Hsuan-Ming; Theodorakis, Emmanuel A.; Haidekker, Mark A

    2010-01-01

    Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer states (TICT) upon photoexcitation. Some classes of molecular rotors, among them those that are built on the benzylidene malononitrile motif, return to the ground state either by nonradiative intramolecular rotation or by fluorescence emission. In low-viscosity solvents, intramolecular rotation dominates, and the fluorescence quantum yield is low. Higher solvent viscosities reduce the intram...

  15. Deblurring molecular images using desorption electrospray ionization mass spectrometry

    Science.gov (United States)

    Parry, R. Mitchell; Galhena, Asiri S.; Fernandez, Facundo M.; Wang, May D.

    2016-01-01

    Traditional imaging techniques for studying the spatial distribution of biological molecules such as proteins, metabolites, and lipids, require the a priori selection of a handful of target molecules. Imaging mass spectrometry provides a means to analyze thousands of molecules at a time within a tissue sample, adding spatial detail to proteomic, metabolomic, and lipidomic studies. Compared to traditional microscopic images, mass spectrometric images have reduced spatial resolution and require a destructive acquisition process. In order to increase spatial detail, we propose a constrained acquisition path and signal degradation model enabling the use of a general image deblurring algorithm. Our analysis shows the potential of this approach and supports prior observations that the effect of the sprayer focuses on a central region much smaller than the extent of the spray. PMID:19963935

  16. Filme, die beflügeln : Einflüsse von Filmen auf die Reisemotivation, Raumwahrnehmung und Imagebildung

    OpenAIRE

    Siehl, Stefan

    2010-01-01

    Populäre Filme, TV-Serien, Werbespots oder bekannte Filmfiguren haben einen enormen Einfluss auf das Image ihrer Schauplätze und auf unsere kulturräumlichen Vorstellungen. Erfolgreiche Filme erreichen ein Millionenpublikum und in der Folge dessen gewinnt Filmtourismus weltweit an Bedeutung. Filme haben sich zu einer Institution für den Tourismusmarkt entwickelt. Ein Grund liegt in der Gemeinsamkeit des Films und der Reise – beide entführen für eine gewisse Zeit aus dem Alltag heraus in eine W...

  17. Molecular imaging of gene expression and protein function in vivo with PET and SPECT.

    Science.gov (United States)

    Sharma, Vijay; Luker, Gary D; Piwnica-Worms, David

    2002-10-01

    Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo. PMID:12353250

  18. Molecular imaging for theranostics in gastroenterology: one stone to kill two birds.

    Science.gov (United States)

    Ko, Kwang Hyun; Kown, Chang-Il; Park, Jong Min; Lee, Hoo Geun; Han, Na Young; Hahm, Ki Baik

    2014-09-01

    Molecular imaging in gastroenterology has become more feasible with recent advances in imaging technology, molecular genetics, and next-generation biochemistry, in addition to advances in endoscopic imaging techniques including magnified high-resolution endoscopy, narrow band imaging or autofluorescence imaging, flexible spectral imaging color enhancement, and confocal laser endomicroscopy. These developments have the potential to serve as "red flag" techniques enabling the earlier and accurate detection of mucosal abnormalities (such as precancerous lesions) beyond biomarkers, virtual histology of detected lesions, and molecular targeted therapy-the strategy of "one stone to kill two or three birds"; however, more effort should be done to be "blue ocean" benefit. This review deals with the introduction of Raman spectroscopy endoscopy, imaging mass spectroscopy, and nanomolecule development for theranostics. Imaging of molecular pathological changes in cells/tissues/organs might open the "royal road" to either convincing diagnosis of diseases that otherwise would only be detected in the advanced stages or novel therapeutic methods targeted to personalized medicine.

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

    NARCIS (Netherlands)

    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 fluoresc

  20. Der Einfluss von Rekrutiererverhaltensweisen auf den Bewerber: Ein mediierter Prozess

    OpenAIRE

    Eberz, Lisa-Marie; Baum, Matthias; Kabst, Rüdiger

    2012-01-01

    In dieser Studie wird die Wirkung der Rekrutiererfreundlichkeit und -kompetenz auf den Bewerber und dessen Absicht, den Bewerbungsprozess weiter zu verfolgen, empirisch analysiert. Als theoretisches Fundament dienen das Signaling und die Theory of Reasoned Action. Unter Zuhilfenahme eines Strukturgleichungsmodells kann gezeigt werden, dass die wahrgenommene Freundlichkeit und Kompetenz des Rekrutierers entgegen bisheriger Annahmen keine direkten Auswirkungen auf den Bewerbungsprozess haben, s...

  1. A DR-WFOI fusion system for the real-time molecular imaging in vivo

    Institute of Scientific and Technical Information of China (English)

    Kun Bi; Xiaochun Xu; Lei Xi; Shaoqun Zeng; Qingming Luo

    2008-01-01

    Digital radiography (DR) and whole-body fluorescent optical imaging (WFOI) have been widely applied in the field of molecular imaging, with the advantages in tissues and functional imaging. The integration of them contributes to the development and discovery of medicine. We introduce an equipment, performance of which is better than that of another molecular imaging system manufactured by Kodak Corp. It can take real-time small animal imaging in vivo, with lower cost and shorter development cycle on the LabVIEW platform. At last, a paradigm experiment on a nude mouse with green fluorescent protein (GFP) transgenic tumor is given to present a real-time DR-WFOI fusion simultaneous image.

  2. 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.

  3. Molecular and functional imaging for detection of lymph node metastases in prostate cancer.

    Science.gov (United States)

    Fortuin, Ansje; Rooij, Maarten de; Zamecnik, Patrik; Haberkorn, Uwe; Barentsz, Jelle

    2013-07-03

    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.

  4. Air flow-assisted ionization imaging mass spectrometry method for easy whole-body molecular imaging under ambient conditions.

    Science.gov (United States)

    Luo, Zhigang; He, Jiuming; Chen, Yi; He, Jingjing; Gong, Tao; Tang, Fei; Wang, Xiaohao; Zhang, Ruiping; Huang, Lan; Zhang, Lianfeng; Lv, Haining; Ma, Shuanggang; Fu, Zhaodi; Chen, Xiaoguang; Yu, Shishan; Abliz, Zeper

    2013-03-01

    Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-to-implement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.

  5. Effect of molecular organization on the image histograms of polarization SHG microscopy

    OpenAIRE

    Psilodimitrakopoulos, Sotiris; Amat Roldán, Iván; Loza Álvarez, Pablo; Artigas García, David

    2012-01-01

    Based on its polarization dependency, second harmonic generation (PSHG) microscopy has been proven capable to structurally characterize molecular architectures in different biological samples. By exploiting this polarization dependency of the SHG signal in every pixel of the image, average quantitative structural information can be retrieved in the form of PSHG image histograms. In the present study we experimentally show how the PSHG image histograms can be affected by the organization of th...

  6. Laser-Induced Electron Diffraction: Inversion of Photoelectron Spectra for Molecular Orbital Imaging

    CERN Document Server

    Puthumpally-Joseph, R; Peters, M; Nguyen-Dang, T T; Atabek, O; Charron, E

    2016-01-01

    In this paper, we discuss the possibility of imaging molecular orbitals from photoelectron spectra obtained via Laser Induced Electron Diffraction (LIED) in linear molecules. This is an extension of our work published recently in Physical Review A \\textbf{94}, 023421 (2016) to the case of the HOMO-1 orbital of the carbon dioxide molecule. We show that such an imaging technique has the potential to image molecular orbitals at different internuclear distances in a sub-femtosecond time scale and with a resolution of a fraction of an Angstr\\"om.

  7. High-order harmonic spectroscopy for molecular imaging of polyatomic molecules

    CERN Document Server

    Negro, M; Faccialà, D; De Silvestri, S; Vozzi, C; Stagira, S

    2014-01-01

    High-order harmonic generation is a powerful and sensitive tool for probing atomic and molecular structures, combining in the same measurement an unprecedented attosecond temporal resolution with a high spatial resolution, of the order of the angstrom. Imaging of the outermost molecular orbital by high-order harmonic generation has been limited for a long time to very simple molecules, like nitrogen. Recently we demonstrated a technique that overcame several of the issues that have prevented the extension of molecular orbital tomography to more complex species, showing that molecular imaging can be applied to a triatomic molecule like carbon dioxide. Here we report on the application of such technique to nitrous oxide (N2O) and acetylene (C2H2). This result represents a first step towards the imaging of fragile compounds, a category which includes most of the fundamental biological molecules.

  8. 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.

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

    International Nuclear Information System (INIS)

    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.

  10. Molecular imaging to target transplanted muscle progenitor cells.

    Science.gov (United States)

    Gutpell, Kelly; McGirr, Rebecca; Hoffman, Lisa

    2013-01-01

    Duchenne muscular dystrophy (DMD) is a severe genetic neuromuscular disorder that affects 1 in 3,500 boys, and is characterized by progressive muscle degeneration. In patients, the ability of resident muscle satellite cells (SCs) to regenerate damaged myofibers becomes increasingly inefficient. Therefore, transplantation of muscle progenitor cells (MPCs)/myoblasts from healthy subjects is a promising therapeutic approach to DMD. A major limitation to the use of stem cell therapy, however, is a lack of reliable imaging technologies for long-term monitoring of implanted cells, and for evaluating its effectiveness. Here, we describe a non-invasive, real-time approach to evaluate the success of myoblast transplantation. This method takes advantage of a unified fusion reporter gene composed of genes (firefly luciferase [fluc], monomeric red fluorescent protein [mrfp] and sr39 thymidine kinase [sr39tk]) whose expression can be imaged with different imaging modalities. A variety of imaging modalities, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and high frequency 3D-ultrasound are now available, each with unique advantages and limitations. Bioluminescence imaging (BLI) studies, for example, have the advantage of being relatively low cost and high-throughput. It is for this reason that, in this study, we make use of the firefly luciferase (fluc) reporter gene sequence contained within the fusion gene and bioluminescence imaging (BLI) for the short-term localization of viable C2C12 myoblasts following implantation into a mouse model of DMD (muscular dystrophy on the X chromosome [mdx] mouse). Importantly, BLI provides us with a means to examine the kinetics of labeled MPCs post-implantation, and will be useful to track cells repeatedly over time and following migration. Our reporter gene approach further allows us to merge multiple imaging modalities in a single living

  11. Relationship between detector size and the need for extra images and their effect on radiation exposure in digital mammography screening; Zusammenhang zwischen der Detektorgroesse und der Notwendigkeit von Zusatzaufnahmen sowie deren Auswirkung auf die Strahlenexposition im digitalen Mammografie-Screening

    Energy Technology Data Exchange (ETDEWEB)

    Entz, K.; Sommer, A. [University Hospital Muenster (Germany). Reference Center for Mammography; Heindel, W. [University Hospital Muenster (Germany). Reference Center for Mammography; University Hospital Muenster (Germany). Dept. of Clinical Radiology; Lenzen, H. [University Hospital Muenster (Germany). Dept. of Clinical Radiology

    2014-09-15

    Purpose: To determine the number of extra images (EI) that are necessary for imaging large breasts when using a detector smaller than 24 cm x 30 cm and to calculate the additional average glandular dose (AGD) for these images. Materials and Methods: The screening mammograms taken between 2007 and 2011 were assessed for a photon counting full-field digital mammography (PCM) system (detector size: 24 cm x 26 cm) and a computed radiography (CR) system (24 cm x 30 cm). The number of EI was recorded and the AGD calculated. This AGD was compared with the mean AGD of 47 conventional full-field digital mammography (FFDM) systems. Results: A total of 62,466 examinations were analyzed. EI had to be taken in 0.6% (199/32,766) of all PCM examinations and 0.3% (90/29 700) of all CR examinations. This corresponded to a total of 327 and 191 EI for the PCM and CR systems, respectively. More than one quarter of the examinations with EI were necessary because the breast was not properly positioned in the original image (PCM 31%, CR 29%). The mean AGD per EI was 0.7 ± 0.1 mGy for the PCM and 2.6 ± 1.2 mGy for the CR system. The mean AGD for all breast thicknesses for FFDM was 1.4 ± 0.3 mGy. Conclusion: In general, large breasts cannot be imaged with just one image per view. The number of examinations where EI are needed is doubled with the 24 cm x 26 cm detector of the PCM system. However, the absolute number is small. The total dose, as the sum of the original and the EI, is equal to the mean AGD of a single image of the FFDM systems and lower than the dose of a single image with the CR system. (orig.)

  12. Bioluminescence: a versatile technique for imaging cellular and molecular features

    Science.gov (United States)

    Paley, Miranda A.

    2016-01-01

    Bioluminescence is a ubiquitous imaging modality for visualizing biological processes in vivo. This technique employs visible light and interfaces readily with most cell and tissue types, making it a versatile technology for preclinical studies. Here we review basic bioluminescence imaging principles, along with applications of the technology that are relevant to the medicinal chemistry community. These include noninvasive cell tracking experiments, analyses of protein function, and methods to visualize small molecule metabolites. In each section, we also discuss how bioluminescent tools have revealed insights into experimental therapies and aided drug discovery. Last, we highlight the development of new bioluminescent tools that will enable more sensitive and multi-component imaging experiments and, thus, expand our broader understanding of living systems.

  13. Laser induced electron diffraction: a tool for molecular orbital imaging

    CERN Document Server

    Peters, Michel; Charron, Eric; Keller, Arne; Atabek, Osman

    2012-01-01

    We explore the laser-induced ionization dynamics of N2 and CO2 molecules subjected to a few-cycle, linearly polarized, 800\\,nm laser pulse using effective two-dimensional single active electron time-dependent quantum simulations. We show that the electron recollision process taking place after an initial tunnel ionization stage results in quantum interference patterns in the energy resolved photo-electron signals. If the molecule is initially aligned perpendicular to the field polarization, the position and relative heights of the associated fringes can be related to the molecular geometrical and orbital structure, using a simple inversion algorithm which takes into account the symmetry of the initial molecular orbital from which the ionized electron is produced. We show that it is possible to extract inter-atomic distances in the molecule from an averaged photon-electron signal with an accuracy of a few percents.

  14. Molecular imaging agents for SPECT (and SPECT/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Gnanasegaran, Gopinath [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); Ballinger, James R. [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2014-05-15

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  15. Molecular probes for nonlinear optical imaging of biological membranes

    Science.gov (United States)

    Blanchard-Desce, Mireille H.; Ventelon, Lionel; Charier, Sandrine; Moreaux, Laurent; Mertz, Jerome

    2001-12-01

    Second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) are nonlinear optical (NLO) phenomena that scale with excitation intensity squared, and hence give rise to an intrinsic 3-dimensional resolution when used in microscopic imaging. TPEF microscopy has gained widespread popularity in the biology community whereas SHG microscopy promises to be a powerful tool because of its sensitivity to local asymmetry. We have implemented an approach toward the design of NLO-probes specifically adapted for SHG and/or TPEF imaging of biological membranes. Our strategy is based on the design of nanoscale amphiphilic NLO-phores. We have prepared symmetrical bolaamphiphilic fluorophores combining very high two-photon absorption (TPA) cross-sections in the visible red region and affinity for cellular membranes. Their incorporation and orientation in lipid membranes can be monitored via TPEF anisotropy. We have also prepared amphiphilic push-pull chromophores exhibiting both large TPA cross-sections and very large first hyperpolarizabilities in the near-IR region. These NLO-probes have proved to be particularly useful for imaging of biological membranes by simultaneous SHG and TPEF microscopy and offer attractive prospects for real-time imaging of fundamental biological processes such as adhesion, fusion or reporting of membrane potentials.

  16. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    Science.gov (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  17. Textsortenklassifikation auf der basus Kommunikativer Grundbedingungen

    Directory of Open Access Journals (Sweden)

    Gabriele Diewald

    1995-12-01

    Full Text Available Im folgenden wird versucht, eine Basisklassifikation von Textsorten zu entwerfen, die umfassend und nichtwillkürlich ist. Mit "umfassend" ist gemeint, daß nicht nur ein bestimmter Ausschnitt aus dem Spektrum möglicher Sprachverwendungen untersucht wird, sondern daß alle Vorkommen dominant sprachlicher Kommunikation, mit denen ein Sprecher normalerweise konfrontiert ist, einbezogen werden.1 Mit "nichtwillkürlich" ist zum einen gemeint, daß die Wahl der Klassifikationskriterien nicht beliebig, sondern aus relevanten, textexternen Faktoren ableitbar ist. 2 Zum anderen betrifft das Problem der Willkürlichkeit die Frage, ob ein Modell die schlüssige Zurückführung von Texteigenschaften auf entsprechende Klassifikationsmerkmale ermöglicht.

  18. Akzent auf die Standardsprachen: Regionale Spuren in

    Directory of Open Access Journals (Sweden)

    Marie-José Kolly

    2013-01-01

    Full Text Available Durch ihren fremdsprachlichen Akzent gibt eine Sprecherin ihre Herkunft, ihre Muttersprache preis. So werden die meisten Deutschschweizer beim Sprechen einer Fremdsprache als solche erkannt. Kann aber aufgrund dieses "Deutschschweizer" Akzents auch erkannt werden, aus welchem Dialektgebiet ein Sprecher stammt? Der vorliegende Beitrag stellt eine empirische Studie zur Perzeption dialektaler Akzente vor. Er beschäftigt sich mit dialektalen Akzenten im Standarddeutschen und im Französischen und zeigt mit quantitativen Methoden auf, dass dialektal bedingte Akzentunterschiede von native speakers durchaus wahrgenommen und lokalisiert werden können. Darüber hinaus und als Basis für die Auswertung des empirischen Teils leistet die vorliegende Arbeit eine Beschreibung und Kategorisierung der dialektalen Lautlandschaft der Schweiz sowie einen Ansatz zur Beschreibung der Aussprache des Französischen durch Schweizer Dialektsprecher.

  19. Quantitative sensing of microviscosity in protocells and amyloid materials using fluorescence lifetime imaging of molecular rotors

    Science.gov (United States)

    Thompson, Alex J.; Tang, T.-Y. Dora; Herling, Therese W.; Che Hak, C. Rohaida; Mann, Stephen; Knowles, Tuomas P. J.; Kuimova, Marina K.

    2014-03-01

    Molecular rotors are fluorophores that have a fluorescence quantum yield that depends upon intermolecular rotation. The fluorescence quantum yield, intensity and lifetime of molecular rotors all vary as functions of viscosity, as high viscosities inhibit intermolecular rotation and cause an increase in the non-radiative decay rate. As such, molecular rotors can be used to probe viscosity on microscopic scales. Here, we apply fluorescence lifetime imaging microscopy (FLIM) to measure the fluorescence lifetimes of three different molecular rotors, in order to determine the microscopic viscosity in two model systems with significant biological interest. First, the constituents of a novel protocell - a model of a prebiotic cell - were studied using the molecular rotors BODIPY C10 and kiton red. Second, amyloid formation was investigated using the molecular rotor Cy3.

  20. Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer

    OpenAIRE

    Wu, Xueming; Burden-Gulley, Susan M.; Yu, Guan-Ping; Tan, Mingqian; Lindner, Daniel; Brady-Kalnay, Susann M.; Lu, Zheng-Rong

    2012-01-01

    Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecula...

  1. 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.

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

    Science.gov (United States)

    Meng, Congsen; Janssen, Maurice H M

    2015-02-01

    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 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. PMID:25725826

  3. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  4. Enhancing contrast and quantitation by spatial frequency domain fluorescence molecular imaging

    Science.gov (United States)

    Sun, Jessica; Hathi, Deep; Zhou, Haiying; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Optical imaging with fluorescent contrast agents is highly sensitive for molecular imaging but is limited in depth to a few centimeters below the skin. Planar fluorescence imaging with full-field, uniform illumination and scientific camera image capture provides a portable and robust configuration for real-time, sensitive fluorescence detection with scalable resolution, but is inherently surface weighted and therefore limited in depth to a few millimeters. At the NIR region (700-1000 nm), tissue absorption and autofluorescence are relatively reduced, increasing depth penetration and reducing background signal, respectively. Optical imaging resolution scales with depth, limiting microscopic resolution with multiphoton microscopy and optical coherence tomography to skin and peri-tumoral tissues are not uniform, varying in thickness and color, complicating subsurface fluorescence measurements. Diffuse optical imaging methods have been developed that better quantify optical signals relative to faster full-field planar reflectance imaging, but require long scan times, complex instrumentation, and reconstruction algorithms. Here we report a novel strategy for rapid measurement of subsurface fluorescence using structured light illumination to improve quantitation of deep-seated fluorescence molecular probe accumulation. This technique, in combination with highly specific, tumor-avid fluorescent molecular probes, will easily integrate noninvasive diagnostics for superficial cancers and fluorescence guided surgery.

  5. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  6. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  7. Molecular fragmentation by recombination with cold electrons studied with a mass sensitive imaging detector

    OpenAIRE

    Mendes, M

    2010-01-01

    The recombination of a molecular cation with a low-energy electron, followed by fragmentation, is a fundamental reaction process in cold and dilute plasmas. For polyatomic ions, it can yield molecular fragments in ro-vibrationally excited states. The discrimination between decay channels with chemically different fragments and the measurement of their excitation energies pose an experimental challenge. This work discusses a new experimental scheme based on fast beam fragment imaging in a stor...

  8. Targeting the treatment of drug abuse with molecular imaging

    International Nuclear Information System (INIS)

    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

  9. Positron emission tomography: diagnostic imaging on a molecular level

    International Nuclear Information System (INIS)

    In human medicine positron emission tomography (PET) is a modern diagnostic imaging method. In the present paper we outline the physical principles of PET and give an overview over the main clinic fields where PET is being used, such as neurology, cardiology and oncology. Moreover, we present a current project in veterinary medicine (in collaboration with the Paul Scherrer Institute and the University Hospital Zurich), where a hypoxia tracer is applied to dogs and cats suffering from spontaneous tumors. Finally new developments in the field of PET were discussed

  10. Molecular imaging of cancer with radiolabeled peptides and PET.

    Science.gov (United States)

    Vāvere, Amy L; Rossin, Raffaella

    2012-06-01

    Radiolabeled peptides hold promise for diagnosis and therapy of cancer as well as for early monitoring of therapy outcomes, patient stratification, etc. This manuscript focuses on the development of peptides labeled with 18F, 64Cu, 68Ga and other positron-emitting radionuclides for PET imaging. The major techniques for radionuclide incorporation are briefly discussed. Then, examples of positron-emitting peptides targeting somatostatin receptors, integrins, gastrin-releasing peptide receptors, vasointestinal peptide receptors, melanocortin 1 receptors and others are reviewed. PMID:22292762

  11. 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.

  12. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

    Science.gov (United States)

    Bhargava, Rohit; Madabhushi, Anant

    2016-07-11

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

  13. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

    Science.gov (United States)

    Bhargava, Rohit; Madabhushi, Anant

    2016-07-11

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

  14. Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2013-01-01

    Full Text Available Neuroendocrine tumors (NETs are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.

  15. Nonlinear optical molecular imaging enables metabolic redox sensing in tissue-engineered constructs

    Science.gov (United States)

    Chen, Leng-Chun; Lloyd, William R.; Wilson, Robert H.; Kuo, Shiuhyang; Marcelo, Cynthia L.; Feinberg, Stephen E.; Mycek, Mary-Ann

    2011-07-01

    Tissue-engineered constructs require noninvasive monitoring of cellular viability prior to implantation. In a preclinical study on human Ex Vivo Produced Oral Mucosa Equivalent (EVPOME) constructs, nonlinear optical molecular imaging was employed to extract morphological and functional information from intact constructs. Multiphoton excitation fluorescence images were acquired using endogenous fluorescence from cellular nicotinamide adenine dinucleotide phosphate [NAD(P)H] and flavin adenine dinucleotide (FAD). The images were analyzed to report quantitatively on tissue structure and metabolism (redox ratio). Both thickness variations over time and cell distribution variations with depth were identified, while changes in redox were quantified. Our results show that nonlinear optical molecular imaging has the potential to visualize and quantitatively monitor the growth and viability of a tissue-engineered construct over time.

  16. Optical-based molecular imaging: contrast agents and potential medical applications

    International Nuclear Information System (INIS)

    Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

  17. 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.

  18. 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 ...).

  19. Molecular targeting of angiogenesis for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brack, Simon S.; Neri, Dario [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich (Switzerland); Dinkelborg, Ludger M. [Research Laboratories of Schering AG, Berlin (Germany)

    2004-09-01

    Angiogenesis, i.e. the proliferation of new blood vessels from pre-existing ones, is an underlying process in many human diseases, including cancer, blinding ocular disorders and rheumatoid arthritis. The ability to selectively target and interfere with neovascularisation would potentially be useful in the diagnosis and treatment of angiogenesis-related diseases. This review presents the authors' views on some of the most relevant markers of angiogenesis described to date, as well as on specific ligands which have been characterised in pre-clinical animal models and/or clinical studies. Furthermore, we present an overview on technologies which are likely to have an impact on the way molecular targeting of angiogenesis is performed in the future. (orig.)

  20. 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

  1. Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Kim, Soonhag

    2016-01-01

    The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h. PMID:26530921

  2. Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Kim, Soonhag

    2016-01-01

    The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h.

  3. Calculation of images of oriented C_60 molecules using molecular orbital theory

    OpenAIRE

    Hands, Ian D; Dunn, Janette L; Bates, Colin A.

    2010-01-01

    Using Hückel molecular-orbital theory, images are created to represent the electron distributions expected for a C60 molecule adsorbed on a substrate. Three different orientations of the C60 molecule on the substrate are considered. The effect of the interaction of the molecule with the substrate is treated purely from the basis of symmetry using group theoretical methods. The resulting electron distributions are then used to generate idealized images which represent how the molec...

  4. Peptide-Targeted Nanoglobular Gd-DOTA Monoamide Conjugates for Magnetic Resonance Cancer Molecular Imaging

    OpenAIRE

    Tan, Mingqian; Wu, Xueming; Jeong, Eun-Kee; Chen, Qianjin; Lu, Zheng-Rong

    2010-01-01

    Effective imaging of cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented in tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by conjugating peptide...

  5. Early Cancer Detection and Targeted Therapy by Magnetic Resonance Molecular Imaging and Nano Medicine

    OpenAIRE

    Li, Zhao

    2015-01-01

    The common theme of my 5-year PhD research is to channel progress in spin physics and nano-bio-materials into meaningful improvements in the theoretical studies, methodological developments, and advanced applications of magnetic resonance (MR) to: 1) MR Molecular Imaging: to detect lesions (especially cancers) at early stages through imaging the existence and locations of physiologically important biomarkers; and2) MR Nano Medicine: to cure diseases (especially cancers) by targeted therapy th...

  6. Adsorptionsmechanismen von Perylen und PTCDA auf Ag(110)

    OpenAIRE

    Ellerbrake, R. (Rainer)

    2003-01-01

    Das Adsorptionsverhalten der aromatischen Kohlenwasserstoffe Perylen und PTCDA, per Vakuumsublimation auf Ag(110) aufgedampft, wird mit experimentellen und theoretischen Methoden untersucht. TDS-, XPS-, STM und LEED-Untersuchungen zeigen, dass sich Perylen auf Ag(110) im Monolagenbereich nahe Raumtemperatur bzgl. der Bedeckung wie ein 2D van der Waals-Gas verhält. Erst nahe der geschlossenen Monolage bilden sich periodische, aber inkommensurable Strukturen aus. Computer...

  7. Flüssigphasenabscheidung von Titandioxid auf Polymerlatex-Templaten

    OpenAIRE

    Strohm, Holger

    2005-01-01

    Es wurde der Einfluss einer Substratfunktionalisierung auf die Flüssigphasenabscheidung von TiO2 auf dispersen Polymerlatexpartikeln in wässriger Lösung untersucht. Als Partikelsubstrate wurden zwei verschiedene Polystyrol-Latizes verwendet: Ein Latex mit einer geringen negativen Oberflächenladungsdichte (PS-Latex) und ein carboxylatfunktionalisierter Latex (PSC-Latex) mit einer hohen Dichte oberflächengebundener Ladungen. Durch die Adsorption von Polyelektrolyten aus wässriger Lösung konnte ...

  8. Untersuchungen zum Einfluss des Eingliederungsalters auf die Fruchtbarkeitsleistung von Jungsauen

    OpenAIRE

    Görtz, Eva Maria

    2014-01-01

    Die Wirtschaftlichkeit der Ferkelerzeugung wird maßgeblich von der Fruchtbarkeitsleistung der Sauenherden bestimmt. Das Ziel der vorliegenden Arbeit bestand darin, einen möglichen Einfluss des Eingliederungsalters auf die Fruchtbarkeitsleistung von Jungsauen zu untersuchen. Mit den Ergebnissen sollten Vorschläge zur Leistungsstabilisierung und Leistungssteigerung der Praxis unterbreitet werden können. Erwartet wurden positive Auswirkungen einer früheren Einstallung der Jungsauen auf die Leist...

  9. Whole-body MR imaging in children with suspected osteonecrosis after intensive chemotherapy: preliminary results; Ganzkoerper-MRT bei Kindern mit Verdacht auf Osteonekrose nach intensiver Chemotherapie: Erste Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Beer, M.; Stenzel, M.; Darge, K. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik; Girschick, H.; Schlegel, P.G. [Universitaetsklinikum Wuerzburg (Germany). Kinderklinik

    2008-03-15

    Purpose: use of multidrug chemotherapy poses the risk of avascular osseous necroses in children. Depiction of the whole body, including clinically non-apparent sites is mandatory for starting early and proper treatment, including surgical approaches in lesions near the joints. We analyzed the value of whole-body MRI in the detection of osteonecrosis, (1) in relation to conventional X-ray imaging and clinical symptoms, (2) using different MRI sequences, (3) with follow-up examinations. Materials and methods: 5 patients suffering from an oncological disease, 13 to 16 years old (3 x ALL, 1 x medulloblastoma, 1 x CML), and recently developing bone pain were examined with X-ray imaging of the particular region and a whole-body MRI (T2w TIRM, T1w TSE sequences, pre- and post-contrast GD-DTPA, including fat suppression techniques). Neck/thorax/abdomen/pelvis, and upper and lower extremities were acquired in the coronal plane, and the feet in sagittal orientation. 4 of 5 patients had at least one follow-up examination (in the mean after 10 {+-} 4 months). Results: none of the initial X-ray images revealed an abnormal finding. The whole-body MRI showed in 4 of 5 children bone marrow lesions compatible with osteonecrosis. The locations were around the knee joints (n = 3) and the tibiae/ankle joints (n = 4). In addition to the symptomatic sites, MRI revealed additional lesions at the following sites: humerus (n = 5), hip joints (n = 4), knee joints (n = 6), ankle joints (n = 4). The size varied from small focal lesions to lesions measuring 90% of the whole transverse diameter of the bone. The lesions were able to be detected most easily with heavily T2-weighted (TIRM) sequences, and the diagnosis was most easily established using the non-enhanced TSE T1-weighted sequences. As a consequence of the results of the whole-body MRI, all patients with lesions compatible with osteonecrosis received symptomatic (n = 2) or specific (n = 2) therapy. In the follow-up examinations, a

  10. Quantitative multicolor compositional imaging resolves molecular domains in cell-matrix adhesions.

    Directory of Open Access Journals (Sweden)

    Eli Zamir

    Full Text Available BACKGROUND: Cellular processes occur within dynamic and multi-molecular compartments whose characterization requires analysis at high spatio-temporal resolution. Notable examples for such complexes are cell-matrix adhesion sites, consisting of numerous cytoskeletal and signaling proteins. These adhesions are highly variable in their morphology, dynamics, and apparent function, yet their molecular diversity is poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: We present here a compositional imaging approach for the analysis and display of multi-component compositions. This methodology is based on microscopy-acquired multicolor data, multi-dimensional clustering of pixels according to their composition similarity and display of the cellular distribution of these composition clusters. We apply this approach for resolving the molecular complexes associated with focal-adhesions, and the time-dependent effects of Rho-kinase inhibition. We show here compositional variations between adhesion sites, as well as ordered variations along the axis of individual focal-adhesions. The multicolor clustering approach also reveals distinct sensitivities of different focal-adhesion-associated complexes to Rho-kinase inhibition. CONCLUSIONS/SIGNIFICANCE: Multicolor compositional imaging resolves "molecular signatures" characteristic to focal-adhesions and related structures, as well as sub-domains within these adhesion sites. This analysis enhances the spatial information with additional "contents-resolved" dimensions. We propose that compositional imaging can serve as a powerful tool for studying complex multi-molecular assemblies in cells and for mapping their distribution at sub-micron resolution.

  11. Molecular Dynamics Study of a Thermal Expansion Coefficient: Ti Bulk with an Elastic Minimum Image Method

    Institute of Scientific and Technical Information of China (English)

    Yakup Hundur; Rainer Hippler; Ziya B. Güven(c)

    2006-01-01

    @@ Linear thermal expansion coefficient (TEC) of Ti bulk is investigated by means of molecular dynamics simulation.The elastic minimum image convention of periodic boundary conditions is introduced to allow the bulk to adjust its size according to the new fixed temperature. The TEC and the specific heat of Ti are compared to the available theoretical and experimental data.

  12. Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA-Programmed Nanoparticle Disassembly.

    Science.gov (United States)

    He, Xuewen; Zeng, Tao; Li, Zhi; Wang, Ganglin; Ma, Nan

    2016-02-24

    Molecular imaging is an essential tool for disease diagnostics and treatment. Direct imaging of low-abundance nucleic acids in living cells remains challenging because of the relatively low sensitivity and insufficient signal-to-background ratio of conventional molecular imaging probes. Herein, we report a class of DNA-templated gold nanoparticle (GNP)-quantum dot (QD) assembly-based probes for catalytic imaging of cancer-related microRNAs (miRNA) in living cells with signal amplification capacity. We show that a single miRNA molecule could catalyze the disassembly of multiple QDs with the GNP through a DNA-programmed thermodynamically driven entropy gain process, yielding significantly amplified QD photoluminescence (PL) for miRNA imaging. By combining the robust PL of QDs with the catalytic amplification strategy, three orders of magnitude improvement in detection sensitivity is achieved in comparison with non-catalytic imaging probe, which enables facile and accurate differentiation between cancer cells and normal cells by miRNA imaging in living cells. PMID:26694689

  13. A synthetic molecular system capable of mirror-image genetic replication and transcription.

    Science.gov (United States)

    Wang, Zimou; Xu, Weiliang; Liu, Lei; Zhu, Ting F

    2016-07-01

    The overwhelmingly homochiral nature of life has left a puzzle as to whether mirror-image biological systems based on a chirally inverted version of molecular machinery could also have existed. Here we report that two key steps in the central dogma of molecular biology, the template-directed polymerization of DNA and transcription into RNA, can be catalysed by a chemically synthesized D-amino acid polymerase on an L-DNA template. We also show that two chirally mirrored versions of the 174-residue African swine fever virus polymerase X could operate in a racemic mixture without significant enantiomeric cross-inhibition to the activity of each other. Furthermore, we demonstrate that a functionally active L-DNAzyme could be enzymatically produced using the D-amino acid polymerase. The establishment of such molecular systems with an opposite handedness highlights the potential to exploit enzymatically produced mirror-image biomolecules as research and therapeutic tools. PMID:27325097

  14. Molecular Imaging Using Fluorescence and Bioluminescence to Reveal Tissue Response to Laser-Mediated Thermal Injury

    Science.gov (United States)

    Mackanos, Mark A.; Jansen, E. Duco; Contag, Christopher H.

    For decades biological investigation has focused on a reductionist approach, which has greatly advanced our understanding of the biological process, but has also served to move the analysis further and further away from the living body. This was necessary as we sought to identify the cells, genes, mutations and/or etiological agents that were associated with a given process. The information generated through these approaches can now be used to advance more integrative strategies in which specific cellular and molecular events can be studied in context of the functional circulation and intact organ systems of living animals, and humans. Essential tools for integrative analyses of biology include imaging modalities that enable visualization of structure and function in the living body. The relatively recent development of molecular probes as exogenous contrast agents and reporter genes that encode proteins with unique properties that can be distinguished from tissues and cells has ushered in a new set of approaches that are being called molecular imaging.

  15. 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.

  16. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    Science.gov (United States)

    Zhang, Guanglei; Pu, Huangsheng; He, Wei; Liu, Fei; Luo, Jianwen; Bai, Jing

    2015-02-01

    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.

  17. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    International Nuclear Information System (INIS)

    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

  18. Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

    Science.gov (United States)

    Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen

    2016-01-01

    Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia. PMID:27621464

  19. 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.

  20. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    International Nuclear Information System (INIS)

    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. 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

  2. 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.

  3. Ratiometric and near-infrared molecular probes for the detection and imaging of zinc ions.

    Science.gov (United States)

    Carol, Priya; Sreejith, Sivaramapanicker; Ajayaghosh, Ayyappanpillai

    2007-03-01

    The detection and imaging of Zn2+ in biological samples are of paramount interest owing to the role of this cation in physiological functions. This is possible only with molecular probes that specifically bind to Zn2+ and result in changes in emission properties. A "turn-on" emission or shift in the emission color upon binding to Zn2+ should be ideal for in vivo imaging. In this context, ratiometric and near-IR probes are of particular interest. Therefore, in the area of chemosensors or molecular probes, the design of fluorophores that allow ratiometric sensing or imaging in the near-IR region is attracting the attention of chemists. The purpose of this Focus Review is to highlight recent developments in this area and stress the importance of further research for future applications.

  4. Molecular Imaging of Bacterial Infections in vivo: The Discrimination between Infection and Inflammation

    Directory of Open Access Journals (Sweden)

    Heather Eggleston

    2014-05-01

    Full Text Available Molecular imaging by definition is the visualization of molecular and cellular processes within a given system. The modalities and reagents described here represent a diverse array spanning both pre-clinical and clinical applications. Innovations in probe design and technologies would greatly benefit therapeutic outcomes by enhancing diagnostic accuracy and assessment of acute therapy. Opportunistic pathogens continue to pose a worldwide threat, despite advancements in treatment strategies, which highlights the continued need for improved diagnostics. In this review, we present a summary of the current clinical protocol for the imaging of a suspected infection, methods currently in development to optimize this imaging process, and finally, insight into endocarditis as a model of infectious disease in immediate need of improved diagnostic methods.

  5. Image-guided Coring for Large-scale Studies in Molecular Pathology.

    Science.gov (United States)

    Montaser-Kouhsari, Laleh; Knoblauch, Nicholas W; Oh, Eun-Yeong; Baker, Gabrielle; Christensen, Stephen; Hazra, Aditi; Tamimi, Rulla M; Beck, Andrew H

    2016-07-01

    Sampling of formalin-fixed paraffin-embedded (FFPE) tissue blocks is a critical initial step in molecular pathology. Image-guided coring (IGC) is a new method for using digital pathology images to guide tissue block coring for molecular analyses. The goal of our study is to evaluate the use of IGC for both tissue-based and nucleic acid-based projects in molecular pathology. First, we used IGC to construct a tissue microarray (TMA); second, we used IGC for FFPE block sampling followed by RNA extraction; and third, we assessed the correlation between nuclear counts quantitated from the IGC images and RNA yields. We used IGC to construct a TMA containing 198 normal and breast cancer cores. Histopathologic analysis showed high accuracy for obtaining tumor and normal breast tissue. Next, we used IGC to obtain normal and tumor breast samples before RNA extraction. We selected a random subset of tumor and normal samples to perform computational image analysis to quantify nuclear density, and we built regression models to estimate RNA yields from nuclear count, age of the block, and core diameter. Number of nuclei and core diameter were the strongest predictors of RNA yields in both normal and tumor tissue. IGC is an effective method for sampling FFPE tissue blocks for TMA construction and nucleic acid extraction. We identify significant associations between quantitative nuclear counts obtained from IGC images and RNA yields, suggesting that the integration of computational image analysis with IGC may be an effective approach for tumor sampling in large-scale molecular studies. PMID:26186251

  6. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    Science.gov (United States)

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    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/. PMID:25022454

  7. 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

    2016-02-11

    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.

  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. 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.

  10. PET for molecular imaging of cancer: a tool for tailored therapy

    International Nuclear Information System (INIS)

    The concept of personalised medicine has led to a need for improved phenotyping as well as prediction of treatment response early after therapy initiation. Most of the molecular biology methods used today need tissue sampling for in vitro analysis. In contrast, molecular imaging allows for non-invasive studies at the molecular level in living, intact organisms. Accordingly, molecular imaging with PET has been one of the most successful techniques in such phenotyping and response prediction using FDG. In addition, recent development of new PET tracers has further improved the value of PET in tumor characterization. Such new PET tracers allow for visualization of tumor specific receptors and tissue characteristics such as ability to metastasize. Furthermore, PET has a high sensitivity and allows for quantification and is not prone to sampling error as seen with biopsies. We will present examples of development of probes targeting the somatostatin receptor type 2, over-expressed in neuroendocrine tumors, including our first-in-man studies of 64Cu-DOTATATE. Also development in probes for visualization of the invasive phenotype will be presented. Finally, with the most recent development of true integrated PET/MRI scanners it has now become possible to add information from MRI. The value of such hybrid imaging will also be briefly discussed. (author)

  11. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared – non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  12. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  13. Rhodopsin molecular contrast imaging by optical coherence tomography for functional assessment of photoreceptors (Conference Presentation)

    Science.gov (United States)

    Nafra, Zahra; Liu, Tan; Jiao, Shuliang

    2016-03-01

    Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. We developed a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption occurs and provides a potentially accurate assessment of rhodopsin content by segmentation of the image at the location. A broadband supercontinuum laser, whose filtered output was centered at 520 nm, was used as the illuminating light source. To test the capabilities of the system on rhodopsin mapping we imaged the retina of albino rats. The rats were dark adapted before imaging. An integrated near infrared OCT was used to guide the alignment in dark. VIS-OCT three-dimensional images were then acquired under dark- and light- adapted states sequentially. Rhodopsin distribution was calculated from the differential image. The rhodopsin distributions can be displayed in both en face view and depth-resolved cross-sectional image. Rhodopsin OCT can be used to quantitatively image rhodopsin distribution and thus assess the distribution of functional rod photoreceptors in the retina. Rhodopsin OCT can bring significant impact into ophthalmic clinics by providing a tool for the diagnosis and severity assessment of a variety of retinal conditions.

  14. 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.

  15. Imaging intracellular viscosity by a new molecular rotor suitable for phasor analysis of fluorescence lifetime.

    Science.gov (United States)

    Battisti, Antonella; Panettieri, Silvio; Abbandonato, Gerardo; Jacchetti, Emanuela; Cardarelli, Francesco; Signore, Giovanni; Beltram, Fabio; Bizzarri, Ranieri

    2013-07-01

    The arsenal of fluorescent probes tailored to functional imaging of cells is rapidly growing and benefits from recent developments in imaging strategies. Here, we present a new molecular rotor, which displays strong absorption in the green region of the spectrum, very little solvatochromism, and strong emission sensitivity to local viscosity. The emission increase is paralleled by an increase in emission lifetime. Owing to its concentration-independent nature, fluorescence lifetime is particularly suitable to image environmental properties, such as viscosity, at the intracellular level. Accordingly, we demonstrate that intracellular viscosity measurements can be efficiently carried out by lifetime imaging with our probe and phasor analysis, an efficient method for measuring lifetime-related properties (e.g., bionalyte concentration or local physicochemical features) in living cells. Notably, we show that it is possible to monitor the partition of our probe into different intracellular regions/organelles and to follow mitochondrial de-energization upon oxidative stress. PMID:23780224

  16. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    Science.gov (United States)

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

  17. 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

  18. Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions.

    Science.gov (United States)

    Shi, Kuangyu; Ziegler, Sibylle I; Vaupel, Peter

    2016-01-01

    Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [(18)F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [(18)F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis. PMID:27526129

  19. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  20. Imaging ion and molecular transport at subcellular resolution by secondary ion mass spectrometry

    Science.gov (United States)

    Chandra, Subhash; Morrison, George H.

    1995-05-01

    The transport of K+, Na+, and Ca2+ were imaged in individual cells with a Cameca IMS-3f ion microscope. Strict cryogenic frozen freeze-dry sample preparations were employed. Ion redistribution artifacts in conventional chemical preparations are discussed. Cryogenically prepared freeze-fractured freeze-dried cultured cells allowed the three-dimensional ion microscopic imaging of elements. As smaller structures in calcium images can be resolved with the 0.5 [mu]m spatial resolution, correlative techniques are needed to confirm their identity. The potentials of reflected light microscopy, scanning electron microscopy and laser scanning confocal microscopy are discussed for microfeature recognition in freeze-fractured freeze-dried cells. The feasibility of using frozen freeze-dried cells for imaging molecular transport at subcellular resolution was tested. Ion microscopy successfully imaged the transport of the isotopically tagged (13C, 15N) amino acid, -arginine. The labeled amino acid was imaged at mass 28 with a Cs+ primary ion beam as the 28(13C15N)- species. After a 4 h exposure of LLC-PK1 kidney cells to 4 mM labeled arginine, the amino acid was localized throughout the cell with a preferential incorporation into the nucleus and nucleolus. An example is also shown of the ion microscopic imaging of sodium borocaptate, an experimental therapeutic drug for brain tumors, in cryogenically prepared frozen freeze-dried Swiss 3T3 cells.

  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 1nM in a 70mm diameter homogeneous phantom, and detection is feasible to near 10pM. 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. 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.

  3. Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors

    OpenAIRE

    Tan Liu; Rong Wen; Lam, Byron L.; Puliafito, Carmen A.; Shuliang Jiao

    2015-01-01

    Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. Here we report a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption oc...

  4. The dopaminergic basis of human behaviors: a review of molecular imaging studies

    OpenAIRE

    Egerton, Alice; Mehta, Mitul A; Montgomery, Andrew J; Lappin, Julia M.; Howes, Oliver D; Reeves, Suzanne J.; Cunningham, Vincent J; Grasby, Paul M.

    2009-01-01

    This systematic review describes human molecular imaging studies which have investigated alterations in extracellular DA levels during performance of behavioral tasks. Whilst heterogeneity in experimental methods limits meta-analysis, we describe the advantages and limitations of different methodological approaches. Interpretation of experimental results may be limited by regional cerebral blood flow (rCBF) changes, head movement and choice of control conditions. We revisit our original study...

  5. Molecular Imaging Approaches to Understanding the Roles of Hydrogen Peroxide Biology in Stress and Development

    OpenAIRE

    Dickinson, Bryan Craig

    2010-01-01

    The production of hydrogen peroxide (H2O2) in biological systems is associated with a variety of pathologies including neurodegenerative diseases, cancer, and the general process of aging. However, a growing body of evidence suggests that the reactivity of this particular reactive oxygen species (ROS) is also harnessed for physiological processes. Molecular imaging using fluorescence microscopy offers a valuable approach for deciphering the multifaceted roles of H2O2 in biological processes. ...

  6. On Sensitivity of Molecular Specific Photoacoustic Imaging Using Plasmonic Gold Nanoparticles

    OpenAIRE

    Mallidi, Srivalleesha; Joshi, Pratixa P.; Sokolov, Konstantin; Emelianov, Stanislav

    2009-01-01

    Functionalized gold nanospheres undergo receptor mediated aggregation on cancer cells that overexpress the epidermal growth factor receptor (EGFR). This phenomenon leads to a red shift in the plasmon resonance frequency of the EGFR-targeted gold nanoparticles. Previously we demonstrated that highly selective detection of cancer cells can be achieved using the combination of multi-wavelength photoacoustic imaging and molecular specific gold nanoparticles. In this study, we use tissue models to...

  7. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

  8. Molecular Sensing and Imaging of Human Disease Cells and Their Responses to Biochemical Stimuli

    OpenAIRE

    Xiao, Lifu

    2015-01-01

    The overall goal of this dissertation is to develop noninvasive imaging techniques that allow us not only to detect diseased cells but also to study the molecular mechanisms underlying these diseases. Atomic force microscopy and Raman spectroscopy are applied to measure cellular mechanical properties (e.g. Young’s Modulus, adhesion force) and biochemical composition of living cancerous vs. healthy (A549 vs. SAEC) human lung epithelial cells. These biomechanical and biochemical properties c...

  9. Development of Laser Desorption Imaging Mass Spectrometry Methods to Investigate the Molecular Composition of Latent Fingermarks

    Science.gov (United States)

    Lauzon, Nidia; Dufresne, Martin; Chauhan, Vinita; Chaurand, Pierre

    2015-06-01

    For a century, fingermark analysis has been one of the most important and common methods in forensic investigations. Modern chemical analysis technologies have added the potential to determine the molecular composition of fingermarks and possibly identify chemicals a suspect may have come into contact with. Improvements in analytical detection of the molecular composition of fingermarks is therefore of great importance. In this regard, matrix-assisted laser desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass spectrometry (IMS) have proven to be useful technologies for fingermark analysis. In these analyses, the choice of ionizing agent and its mode of deposition are critical steps for the identification of molecular markers. Here we propose two novel and complementary IMS approaches for endogenous and exogenous substance detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix and silver sputtering.

  10. IMAGING OF THE CCS 22.3 GHz EMISSION IN THE TAURUS MOLECULAR CLOUD COMPLEX

    International Nuclear Information System (INIS)

    Thioxoethenylidene (CCS) is an abundant interstellar molecule and a good tracer of high density and evolutionary stage of dense molecular clouds. It is also a suitable candidate for Zeeman splitting observations for its high splitting factor and narrow thermal line widths. We report here Expanded Very Large Array 22.3 GHz observations of three dense molecular cores TMC-1, TMC-1C, and L1521B in the Taurus molecular cloud complex to image the CCS 21-10 transition. For all three sources, the clumpy CCS emission is most likely tracing the starless cores. However, these compact structures account for only ∼1%-13% of the integrated emission detected in single-dish observations, indicating the presence of significant large-scale diffuse emission in favorable conditions for producing CCS.

  11. Imaging of the CCS 22.3 GHz emission in the Taurus Molecular Cloud complex

    CERN Document Server

    Roy, Nirupam; Momjian, Emmanuel; Sarma, Anuj P

    2011-01-01

    Thioxoethenylidene (CCS) is an abundant interstellar molecule, and a good tracer of high density and evolutionary stage of dense molecular clouds. It is also a suitable candidate for Zeeman splitting observations for its high splitting factor and narrow thermal linewidths. We report here EVLA 22.3 GHz observations of three dense molecular cores TMC-1, TMC-1C and L1521B in the Taurus Molecular Cloud complex to image the CCS 2_1-1_0 transition. For all three sources, the clumpy CCS emission is most likely tracing the starless cores. However, these compact structures account for only ~ 1-13% of the integrated emission detected in single-dish observations, indicating the presence of significant large scale diffuse emission in favorable conditions for producing CCS.

  12. Molecular imaging of plaques in coronary arteries with PET and SPECT

    Institute of Scientific and Technical Information of China (English)

    Zhong-Hua SUN; Hairil Rashmizal; Lei XU

    2014-01-01

    Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography (PET) and single photon emission computed tomography (SPECT) has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.

  13. Application of Machine Learning tools to recognition of molecular patterns in STM images

    Science.gov (United States)

    Maksov, Artem; Ziatdinov, Maxim; Fujii, Shintaro; Kiguchi, Manabu; Higashibayashi, Shuhei; Sakurai, Hidehiro; Kalinin, Sergei; Sumpter, Bobby

    The ability to utilize individual molecules and molecular assemblies as data storage elements has motivated scientist for years, concurrent with the continuous effort to shrink a size of data storage devices in microelectronics industry. One of the critical issues in this effort lies in being able to identify individual molecular assembly units (patterns), on a large scale in an automated fashion of complete information extraction. Here we present a novel method of applying machine learning techniques for extraction of positional and rotational information from scanning tunneling microscopy (STM) images of π-bowl sumanene molecules on gold. We use Markov Random Field (MRF) model to decode the polar rotational states for each molecule in a large scale STM image of molecular film. We further develop an algorithm that uses a convolutional Neural Network combined with MRF and input from density functional theory to classify molecules into different azimuthal rotational classes. Our results demonstrate that a molecular film is partitioned into distinctive azimuthal rotational domains consisting typically of 20-30 molecules. In each domain, the ``bowl-down'' molecules are generally surrounded by six nearest neighbor molecules in ``bowl-up'' configuration, and the resultant overall structure form a periodic lattice of rotational and polar states within each domain. Research was supported by the US Department of Energy.

  14. Nonlinear microrheology and molecular imaging to map microscale deformations of entangled DNA networks

    Science.gov (United States)

    Wu, Tsai-Chin; Anderson, Rae

    We use active microrheology coupled to single-molecule fluorescence imaging to elucidate the microscale dynamics of entangled DNA. DNA naturally exists in a wide range of lengths and topologies, and is often confined in cell nucleui, forming highly concentrated and entangled biopolymer networks. Thus, DNA is the model polymer for understanding entangled polymer dynamics as well as the crowded environment of cells. These networks display complex viscoelastic properties that are not well understood, especially at the molecular-level and in response to nonlinear perturbations. Specifically, how microscopic stresses and strains propagate through entangled networks, and what molecular deformations lead to the network stress responses are unknown. To answer these important questions, we optically drive a microsphere through entangled DNA, perturbing the system far from equilibrium, while measuring the resistive force the DNA exerts on the bead during and after bead motion. We simultaneously image single fluorescent-labeled DNA molecules throughout the network to directly link the microscale stress response to molecular deformations. We characterize the deformation of the network from the molecular-level to the mesoscale, and map the stress propagation throughout the network. We further study the impact of DNA length (11 - 115 kbp) and topology (linear vs ring DNA) on deformation and propagation dynamics, exploring key nonlinear features such as tube dilation and power-law relaxation.

  15. Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

    Directory of Open Access Journals (Sweden)

    Balasundaram G

    2015-01-01

    Full Text Available Ghayathri Balasundaram,1,* Chris Jun Hui Ho,1,* Kai Li,2 Wouter Driessen,3 US Dinish,1 Chi Lok Wong,1 Vasilis Ntziachristos,3 Bin Liu,2 Malini Olivo1,41Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC, 2Institute of Materials Research and Engineering (IMRE, Agency for Science, Technology and Research (A*STAR, Singapore; 3Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany; 4School of Physics, National University of Ireland, Galway, Ireland *These authors contributed equally to this work Abstract: Conjugated polymers (CPs are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used

  16. Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

    Science.gov (United States)

    Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C; Merk, Denis R; Lyons, Jennifer K; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N; Ray, Pritha; Patel, Manishkumar; Chang, Ya-Fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C; Dash, Rajesh; Yang, Phillip C; Brinton, Todd J; Yock, Paul G; McConnell, Michael V; Gambhir, Sanjiv S

    2016-09-01

    Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:27332865

  17. Maria Montessori und das Recht der Kinder auf Bildung

    OpenAIRE

    Dieter, Anne

    2007-01-01

    Vor einhundert Jahren eröffnete die Wissenschaftlerin und Sozialreformerin Dr. med. Maria Montessori in Rom ihre erste Kindertagesstätte, das „Casa dei Bambini”. Inzwischen gibt es allein in Deutschland ca. eintausend Kindergärten und auch Schulen, die nach ihrem Konzept arbeiten. Der Beitrag will auf die Zusammenhänge zwischen dem Menschenrecht auf Bildung, dem pädagogischen Konzept der Maria Montessori und ihrem natur- und verhaltenswissenschaftlich begründeten Ansatz der Lernforschung hinw...

  18. Zum Unternehmerhabitus. Eine kultursoziologische Bestimmung im Hinblick auf Schumpeter

    OpenAIRE

    Loer, Thomas

    2006-01-01

    Unternehmerisches Handeln ist soziologisch gesehen ein Typus des Handelns, der unter den Bedingungen der Moderne exemplarisch für Handeln überhaupt stehen kann, verbindet es doch Freimut zu riskanter Entscheidung mit dem Anspruch auf rationale Verlässlichkeit: Der Unternehmer kann ebenso wenig umhin, Neuerungen zu suchen und zu fördern wie er dabei auf berechnende Berücksichtigung und materiale Würdigung seiner Möglichkeiten und der Erfolgschancen seines Handelns verzichten kann. Um so handel...

  19. Enantioselektive katalytische Hydrierung mit polymerfixiertem Katalysator auf einer Kieselgurmatrix

    OpenAIRE

    Jaser, Karl

    2004-01-01

    Diese Arbeit beschäftigt sich mit der Fixierung des enantioselektiven Rhodium-Pyrphos-Katalysators auf einer inerten Kieselgurmatrix. Dabei wird als Polymer Glycerin-tris[polypropylenglycol-amingestoppt]-ether verwendet, das mit 1,3,5-Benzoltricarbonsäure-trichlorid oder 1,6-Diisocyanato-hexan vernetzt wird. Die Hydrierdauer einer bestimmten Menge Acetamidozimtsäure, der Umsatz und der ee-Wert, die im Batch-Betrieb ermittelt wurden, lassen einen Rückschluss auf die Menge des reaktiven Rhodium...

  20. Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT.

    Science.gov (United States)

    Silindir, Mine; Erdoğan, Suna; Özer, A Yekta; Doğan, A Lale; Tuncel, Murat; Uğur, Ömer; Torchilin, Vladimir P

    2013-03-01

    Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG(2000)-PE:Chol:DTPA-PE), (PL 90G:PEG(2000)-PE:Chol:DTPA-PE), (DPPC:PEG(2000)-PE:Chol:PAPs), (PL 90G:PEG(2000)-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3-8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging. PMID:23078019

  1. The development of EGFR molecular imaging and gene mutation in non-small cell lung cancer

    International Nuclear Information System (INIS)

    In vivo epidermal growth factor receptor (EGFR) imaging has great potential to affect patient-specific treatment for NSCLC, applying a targeted therapy, and measuring molecular-specific effects of treatment. New PET/CT radiotracers,such as N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl) methoxy]quinazolin-4-amine (ZD6476), five 4-(anilino) quinazoline derivatives (ML01) and 4-[(3-iodophenyl) amino]-7-(2-[2-{2-(2-[2-{2-([18F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)- ethoxy }-ethoxy]-quinazoline-6-yl-acrylamide) ([18F]F-PEG6-IPQA) are now available. But, 11C labeled-4-N-(3-bromoanilino)-6, 7-dimethoxyquinazoline (PD153035) is the only PET/CT radiotracer used for human clinical evaluation,primarily for EGFR imaging. Finally, the most important aspect of successful imaging is the identification and characterization of EGFR at the cellular or sub-cellular level with high specificity for the target. Considering the need for further development of such PET/CT tracers, EGFR molecular imaging will be presented along with an important examination of the progression that has been made thus far in the field. (authors)

  2. Der westliche Blick auf den Orient The Western Gaze on the Orient

    Directory of Open Access Journals (Sweden)

    Antje Schrupp

    2007-11-01

    Full Text Available Angesichts der aktuellen Debatten über den Islam zeigen Christina von Braun und Bettina Mathes die viele Jahrhunderte alte Interpretationsgeschichte des Orients aus westlicher Perspektive auf. In ihrem materialreichen Band schildern sie die historische und geografische Vielfalt des Phänomens „Islam“ und zeigen, wie westliches Selbstverständnis und Projektionen das Bild des Okzidents vom Orient seit langem und bis heute prägen – auch da, wo man es auf den ersten Blick nicht vermuten würde.In the face of current debates on the subject of Islam, Christina von Braun and Bettina Mathes point to the centuries-old history of interpreting the orient from the western perspective. The material-rich volume sketches the historical and geographical diversity of the phenomenon of “Islam,” showing how the western world has long taken for granted their projection of an image of the occidental orient and how these images persist, even where they might be least expected.

  3. Assessment of clinical image quality in feline chest radiography with a needle-image plate (NIP) storage phosphor system. An approach to the evaluation of image quality in neonatal radiography; Untersuchungen zur Qualitaet von Thoraxaufnahmen bei Katzen mit einem auf einer Nadelstruktur basierenden Speicherfoliensystem. Modelluntersuchungen zur Bewertung der Bildqualitaet bei Neugeborenen

    Energy Technology Data Exchange (ETDEWEB)

    Ludewig, E.; Bosch, B.; Gaebler, K.; Succow, D.; Werrmann, A. [Klinik fuer Kleintiere, Univ. Leipzig (Germany); Hirsch, W.; Sorge, I. [Abt. Paediatrische Radiologie, Univ. Leipzig (Germany); Gosch, D. [Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Univ. Leipzig (Germany)

    2010-02-15

    Purpose: Is the image quality of thoracic radiographs of cats obtained with a needle-based storage phosphor (NIP) system superior to conventional (PIP) storage phosphor radiography? Is it possible to decrease the mAs by 50% with the NIP system without significant loss of information? Materials and Methods: From each of the 20 animals, three lateral radiographs were acquired. The assessment of the exposure level was based on the generated IgM-values. Images were acquired 1. with the NIP system and exposure settings equivalent to an IgM of 1.9, 2. with the PIP system and identical settings, and 3. with the NIP system and 50% of the mAs. Six blinded readers used a 5-step scale to assess the reproducibility of five anatomical structures and image noise sensation. Data were analysed using Visual Grading Characteristics Analysis (VGC). Results: While applying identical exposure values the NIP system for all features revealed superior ratings to those of the PIP system (AUC{sub VGC} values ranged from 0.81 for ''cardiac silhouette'' to 0.92 for ''trachea''). Even when reducing mAs by 50% in the NIP images all features were rated better compared with the PIP images and original settings (AUC{sub VGC} values ranged from 0.60 for ''cardiac silhouette'' to 0.74 for ''trachea'' and ''caudal thoracic field''). Conclusion: The NIP system demonstrates clearly better image quality compared to the reference PIP system. A dose reduction of 50% seems to be possible without relevant detraction from image quality. The results obtained in the animal model are valid for simulating conditions in neonatal radiological practise. (orig.)

  4. Pushing CT and MR Imaging to the Molecular Level for Studying the “Omics”: Current Challenges and Advancements

    Directory of Open Access Journals (Sweden)

    Hsuan-Ming Huang

    2014-01-01

    Full Text Available During the past decade, medical imaging has made the transition from anatomical imaging to functional and even molecular imaging. Such transition provides a great opportunity to begin the integration of imaging data and various levels of biological data. In particular, the integration of imaging data and multiomics data such as genomics, metabolomics, proteomics, and pharmacogenomics may open new avenues for predictive, preventive, and personalized medicine. However, to promote imaging-omics integration, the practical challenge of imaging techniques should be addressed. In this paper, we describe key challenges in two imaging techniques: computed tomography (CT and magnetic resonance imaging (MRI and then review existing technological advancements. Despite the fact that CT and MRI have different principles of image formation, both imaging techniques can provide high-resolution anatomical images while playing a more and more important role in providing molecular information. Such imaging techniques that enable single modality to image both the detailed anatomy and function of tissues and organs of the body will be beneficial in the imaging-omics field.

  5. Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors

    Science.gov (United States)

    Liu, Tan; Wen, Rong; Lam, Byron L.; Puliafito, Carmen A.; Jiao, Shuliang

    2015-09-01

    Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. Here we report a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption occurs and provides a potentially accurate assessment of rhodopsin content by segmentation of the image at the location. Rhodopsin OCT can be used to quantitatively image rhodopsin distribution and thus assess the distribution of functional rod photoreceptors in the retina. Rhodopsin OCT can bring significant impact into ophthalmic clinics by providing a tool for the diagnosis and severity assessment of a variety of retinal conditions.

  6. Preparation of lisinopril-capped gold nanoparticles for molecular imaging of angiotensin-converting enzyme

    Science.gov (United States)

    Li, Yuan; Baeta, Cesar; Aras, Omer; Daniel, Marie-Christine

    2009-05-01

    Overexpression of angiotensin-converting enzyme (ACE) has been associated with the pathophysiology of cardiac and pulmonary fibrosis. Moreover, the prescription of ACE inhibitors, such as lisinopril, has shown a favorable effect on patient outcome for patients with heart failure or systemic hypertension. Thus targeted imaging of the ACE would be of crucial importance for monitoring tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-coated gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. The preparation involved non-modified lisinopril, using its primary amine group as the anchoring function on the gold nanoparticles surface. The stable lisinopril-coated gold nanoparticles obtained were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). Their zeta potential was also measured in order to assess the charge density on the modified gold nanoparticles (GNPs).

  7. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.

    Science.gov (United States)

    Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (ptranslation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  8. 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.

  9. Preanalytical considerations in detection of colorectal cancer in blood serum using Raman molecular imaging (Conference Presentation)

    Science.gov (United States)

    Treado, Patrick J.; Stewart, Shona D.; Smith, Aaron; Kirschner, Heather; Post, Christopher; Overholt, Bergein F.

    2016-03-01

    Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. Raman Molecular Imaging (RMI) is an effective technique to evaluate human tissue, cells and bodily fluids, including blood serum for disease diagnosis. ChemImage Corporation, in collaboration with clinicians, has been engaged in development of an in vitro diagnostic Raman assay focused on CRC detection. The Raman Assay for Colorectal Cancer (RACC) exploits the high specificity of Raman imaging to distinguish diseased from normal dried blood serum droplets without additional reagents. Pilot Study results from testing of hundreds of biobank patient samples have demonstrated that RACC detects CRC with high sensitivity and specificity. However, expanded clinical trials, which are ongoing, are revealing a host of important preanalytical considerations associated with sample collection, sample storage and stability, sample shipping, sample preparation and sample interferents, which impact detection performance. Results from recent clinical studies will be presented.

  10. Einflüsse von Umweltvariablen und Fahrereigenschaften auf die Wahl der Geschwindigkeit im Kraftfahrzeug

    OpenAIRE

    Brandenburg, Stefan

    2014-01-01

    Welche Geschwindigkeit wählen Sie auf einer Landstraße? Welche auf einer Autobahn? Sicherlich werden Ihre Antworten auf beide Fragen ähnlich lauten, beispielsweise: Kommt darauf an, welches Geschwindigkeitslimit gilt. Genau diese beispielhafte Antwort fanden bereits empirische Untersuchungen zu dieser Fragestellung (z. B. vanNes, Brandenburg & Twisk, 2008, 2010). Nach den Ergebnissen dieser Untersuchungen stellt das jeweilige Geschwindigkeitslimit den größten Einfluss auf die Wahl der Geschwi...

  11. 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

  12. Determinanten der technischen Sozialisation - Einflussfaktoren auf die MINT-Studienwahl

    OpenAIRE

    Pfenning, Uwe

    2014-01-01

    Darstellung und Diskussion der zentralen Determinanten der Berufsfindung für MINT-Berufe und zur Definition zum MINT-Beurfen in der Moderne unter Bezugnahme auf Aspekte der Technikemanzipation von den Naturwissenschaften, der Techniksozialisation als Findungsprozess zwischen eigenen Talenten und externen Anforderungsprofilen sowie der Technikmündigkeit als Leitbild der Moderne.

  13. Schaltbare supramolekulare Organisation strukturdefinierter Micellen basierend auf einem amphiphilen Fulleren

    OpenAIRE

    Burghardt, Stephan; Hirsch, Andreas; Schade, Boris; Ludwig, Kai; Böttcher, Christoph

    2013-01-01

    Jeweils exakt acht amphiphile Fullerendendrimer-Moleküle bilden spontan in wässriger Lösung Micellen, deren Auf- und Abbau durch einen externen Stimulus (pH-Wert) geschaltet werden kann. Die bemerkenswerte Strukturpersistenz der Micellen ermöglicht die Bestimmung ihrer dreidimensionalen Organisation aus kryo-transmissionselektronenmikroskopischen Aufnahmen und damit die Modellierung der molekularen Architektur.

  14. Auswirkung der Studienberatung auf Studierverhalten, Studiergewohnheiten und Leistungsmotivation von Studierenden

    OpenAIRE

    Ghulam, Mustafa

    2014-01-01

    Einleitung: Warum Studierenden sich an die Studienberatung wenden und welchen geschichtlichen Hintergrund die Institution der Studienberatung hat, wurde bereits erforscht, aber die genaue Umsetzung und die genauen Auswirkungen auf Studierverhalten, Studiergewohnheiten und Leistungsmotivation von Studierenden stellen Forschungslücken dar. Diesen Aspekten wird im Rahmen der vorliegenden Arbeit nachgegangen. Methoden: Mit 36 Studierenden aus den Bachelorstudiengängen (Betriebswirtschaftslehre, ...

  15. Uneinheitliche Entwicklungen auf dem sächsischen Arbeitsmarkt

    OpenAIRE

    Michael Weber

    2015-01-01

    Seit Jahresbeginn wurde auf dem sächsischen und dem gesamten ostdeutschen Arbeitsmarkt die sozialversicherungspflichtige Beschäftigung weiter ausgebaut, während die geringfügige Beschäftigung zurückgefahren wurde. Auch die saisonbereinigte Zahl der freien Stellen ist erstmals seit anderthalb Jahren wieder rückläufig.

  16. Nährwertkennzeichnung und ihr Einfluss auf das Verbraucherverhalten

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Storcksdieck, Stefan

    2009-01-01

    , die an prominenter Stelle auf der Vorderseite der Verpackung angebracht werden. Neuere Forschung zeigt, dass die meisten Verbraucher in der Lage sind, solche Informationen korrekt zu verarbeiten, dass aber nur eine Minderheit der Verbraucher dies im Geschäft auch tut. Die entscheidende Frage der...

  17. Observing molecular dynamics with time-resolved 3D momentum imaging

    Science.gov (United States)

    Sturm, F. P.; Wright, T.; Bocharova, I.; Ray, D.; Shivaram, N.; Cryan, J.; Belkacem, A.; Weber, T.; Dörner, R.

    2014-05-01

    Photo-excitation and ionization trigger rich dynamics in molecular systems which play a key role in many important processes in nature such as vision, photosynthesis or photoprotection. Observing those reactions in real-time without significantly disturbing the molecules by a strong electric field has been a great challenge. Recent experiments using Time-of-Flight and Velocity Map Imaging techniques have revealed important information on the dynamics of small molecular systems upon photo-excitation. We have developed an apparatus for time-resolved momentum imaging of electrons and ions in all three spatial dimensions that employs two-color femtosecond laser pulses in the vacuum and extreme ultraviolet (VUV, XUV) for probing molecular dynamics. Our COLTRIMS style reaction microscope can measure electrons and ions in coincidence and reconstruct the momenta of the reaction fragments in 3D. We use a high power 800 nm laser in a loose focusing geometry gas cell to efficinetly drive High Harmonic Generation. The resulting photon flux is sufficient to perform 2-photon pump-probe experiments using VUV and XUV pulses for both pump and probe. With this setup we investigate non-Born-Oppenheimer dynamics in small molecules such as C2H4 and CO2 on a femtosecond time scale. Supported by Chemical Sciences, Geosciences and Biosciences division of BES/DOE.

  18. 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.

  19. Light at the end of the tunnel in radiation therapy: molecular imaging in radiation research

    International Nuclear Information System (INIS)

    Accurate dose delivery to malignant tissue in radiotherapy is quite important for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, we demonstrated that molecular probes can monitor radiation-induced physiological changes at the target and off-target sites using in vivo molecular imaging approaches. Further we show endogenous bioluminescence resulting from whole body irradiation, which is distinct from the Cherenkov radiation. Mice without anesthesia were held in ventilated mouse pie cage and subjected to 5 Gy X-ray irradiation using commercially available X-RAD320 irradiator (1 Gy/min; F2 beam hardening filter 1.5 mm Al, 0.25 mm Cu, 0.75 mm Sn,). The endogenous bioluminescence from the subjects was captured using cooled CCD camera. Significant increase (up to 100 fold) in the amounts of photons released as bioluminescence was detected during 5 min capture from the mice subjected to irradiation compared to that of the control. To determine the early inflammatory response, the reactive oxygen species (ROS) activity was monitored using L-012 (8-amino-5-chloro-7-phenylpyridol (3,4-d)pyridazine-1,4(2H,3H) dione), a chemiluminescence reporter. L-012 was administered (i.p) after 15 min of irradiation. Chemiluminescence resulting from the irradiation induced ROS activity, possible through the action of the

  20. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    Science.gov (United States)

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer. PMID:26961312

  1. 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.

  2. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    Science.gov (United States)

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

  3. Advances of molecular imaging probes for the diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Zhou, Ming; Wang, Xiaobo; Liu, Zhiguo; Yu, Lun; Hu, Shuo; Chen, Lizhang; Zeng, Wenbin

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains and it becomes the most common cause of dementia in the elderly. There is an urgent need for the early diagnosis and treatment of AD to ease caregiver burden and medical costs, as well as improve patients' living activities associated with the dramatic increasing number of affected individuals. Molecular imaging with target-specific probes is contributing to identify the underlying biology in AD, which benefits to the early diagnosis of AD and the evaluation of anti-AD therapy. Molecular imaging probes, such as (11)C-PIB, (11)C-MP4A, (18)F-AV-45, and (11)F-FDG, can selectively bind to special bimolecular of AD or accurately accumulate at the location of damage areas, thus become an edge tool for a better management of the diseases in the clinical practice and new drug development. In the past decades, a large variety of probes is being developed and tested to be useful for the early and accurate diagnosis of Alzheimer's disease, patient selection for disease-modifying therapeutic trials and monitoring the effect of anti-amyloid therapy. Since imaging probes may also help to guide physicians to identify those patients that could best benefit from a given therapeutic regimen, dose, or duration of drug, this paper is to present a perspective of the available imaging probes for AD, classified on different modalities. Meanwhile, recent advances of those probes that have been selected for clinical trials and are at the different stages of the US Food and Drugs Administration (FDA) approval are outlined. Additionally, future directions and specific application of imaging strategies designed for both diagnosis and treatment for AD are discussed. PMID:24484277

  4. Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

    Science.gov (United States)

    Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

  5. Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hoeben, Bianca A. W.; Bussink, Johan; Kaanders, Johannes H. A. M. [Dept. of Radiation Oncology, Radboud Univ. Nijmegen Medical Centre, Nijmegen (Netherlands)], e-mail: b.hoeben@rther.umcn.nl; Oyen, Wim J. G. [Dept. of Nuclear Medicine, Radboud Univ. Nijmegen Medical Centre, Nijmegen (Netherlands); Troost, Esther G. C. [Maastro Clinic, GROW School for Oncology and Developmental Biology, Maastricht Univ. Medical Centre, Maastricht (Netherlands)

    2013-10-15

    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 18F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  6. A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems

    International Nuclear Information System (INIS)

    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 PhantomTM), 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 pinhole

  7. 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

  8. Einfluss von DNA-Variationen auf die koronare Herzerkrankung

    Directory of Open Access Journals (Sweden)

    Drexel H

    2008-01-01

    Full Text Available Erkenntnisse aus Familien- oder Zwillingsstudien lassen auf einen hohen genetischen Hintergrund der koronaren Herzerkrankung (KHK schließen. Seit einiger Zeit versucht man mittels intensiver Forschung, die genetischen Faktoren, welche das kardiovaskuläre Risiko beeinflussen, zu identifizieren. Aufgrund der hohen Frequenz der KHK in der Bevölkerung spielen hierbei Mendel’sche Erkrankungen, wie die familiäre Hypercholesterinämie, nur eine untergeordnete Rolle. Anhand der Ergebnisse aus Kopplungs- und Assoziationsstudien sind bisher zahlreiche DNA-Polymorphismen in Kandidatengenen als potenzielle genetische Risikofaktoren für die KHK vorgeschlagen worden. Die möglichen Auswirkungen dieser Polymorphismen auf das Erkrankungsrisiko werden in der Literatur allerdings meist kontrovers diskutiert. Metaanalysen haben gezeigt, dass DNA-Polymorphismen der Gene für Apolipoprotein E, Cholesteryl Ester Transfer-Protein, Faktor V, Prothrombin und Adiponektin einen signifikanten Zusammenhang mit der KHK aufweisen. Die jüngste Entwicklung von technischen Verfahren für die Hochdurchsatzgenotypisierung sowie die wachsende Kenntnis um die Strukturierung des Genoms in Haplotypen eröffnete der Forschung neue Möglichkeiten für die Ermittlung des genetischen Einflusses auf die KHK. Infolgedessen konnten mehrere unabhängig durchgeführte genomweite Assoziationsstudien den chromosomalen Abschnitt 9p21 erstmalig als genetischen Modulator für die KHK identifizieren. Die genaue Wirkweise dieser in der Region 9p21 lokalisierten DNA-Variationen auf die Entstehung der KHK ist bis dato allerdings unbekannt. Zukünftige technologische Entwicklungen, wie das "next generation sequencing", werden innerhalb absehbarer Zeit die Forschung über den Zusammenhang zwischen genetischer Variabilität und der KHK weiter maßgeblich beeinflussen. Durch dieses Wissen wird es uns gelingen, das KHK-Risiko besser abschätzen zu können und neue Therapien auf Personen mit hohem

  9. Molecular Imaging in Preclinical Models of IBD with Nuclear Imaging Techniques: State-of-the-Art and Perspectives.

    Science.gov (United States)

    Kaaru, Eric; Bianchi, Andrea; Wunder, Andreas; Rasche, Volker; Stiller, Detlef

    2016-10-01

    Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is characterized by chronic unregulated inflammation of the intestinal mucosa of the gastrointestinal tract. To date, this pathology has no cure. Colonoscopy and biopsies are the current gold standard diagnostic tools. However, being a chronic disease, IBD requires continuous follow-up to check for disease progress, treatment response, and remission. Unfortunately, these 2 diagnostic procedures are invasive and generally unable to show the cellular and molecular changes that take place in vivo. In this context, it is clear that there is a strong need for optimized noninvasive imaging techniques able to overcome the aforementioned limitations. This review aims to bring to light the scientific advancements that have been achieved so far in nuclear medicine in relation to tracking of immune cells involved in the preclinical models of IBD. In particular, this review will explore the advantages and limitations of the radiopharmaceuticals that aim to track whole cells like neutrophils, those that involve the radiolabeling of immune cell substrates or available human IBD medical therapies, and those that aim to track cell signaling molecules (e.g., cytokines and cell adhesion molecules). After a detailed critical summary of the state-of-the art, the challenges and perspectives of molecular imaging applied to IBD studies will be analyzed. Special attention will be paid to the translational potential of the described techniques and on the potential impact of these innovative approaches on the drug discovery pipelines and their contribution to the evolution of personalized medicine. PMID:27580387

  10. Diffractive imaging of a molecular rotational wavepacket with femtosecond Megaelectronvolt electron pulses

    CERN Document Server

    Yang, Jie; Vecchione, Theodore; Robinson, Matthew S; Li, Renkai; Hartmann, Nick; Shen, Xiaozhe; Coffee, Ryan; Corbett, Jeff; Fry, Alan; Gaffney, Kelly; Gorkhover, Tais; Hast, Carsten; Jobe, Keith; Makasyuk, Igor; Reid, Alexander; Robinson, Joseph; Vetter, Sharon; Wang, Fenglin; Weathersby, Stephen; Yoneda, Charles; Centurion, Martin; Wang, Xijie

    2015-01-01

    Imaging changes in molecular geometries on their natural femtosecond timescale with sub-Angstrom spatial precision is one of the critical challenges in the chemical sciences, since the nuclear geometry changes determine the molecular reactivity. For photoexcited molecules, the nuclear dynamics determine the photoenergy conversion path and efficiency. We performed a gas-phase electron diffraction experiment using Megaelectronvolt (MeV) electrons, where we captured the rotational wavepacket dynamics of nonadiabatically laser-aligned nitrogen molecules. We achieved an unprecedented combination of 100 fs root-mean-squared (RMS) temporal resolution and sub-Angstrom (0.76 {\\AA}) spatial resolution that makes it possible to resolve the position of the nuclei within the molecule. In addition, the diffraction patterns reveal the angular distribution of the molecules, which changes from prolate (aligned) to oblate (anti-aligned) in 300 fs. Our results demonstrate a significant and promising step towards making atomical...

  11. MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery.

    Science.gov (United States)

    Gessel, Megan M; Norris, Jeremy L; Caprioli, Richard M

    2014-07-31

    Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses to provide unbiased visualization of the arrangement of biomolecules in tissue. As such, MALDI IMS has the capability to become a powerful new molecular technology for the biological and clinical sciences. In this review, we briefly describe several applications of MALDI IMS covering a range of molecular weights, from drugs to proteins. Current limitations and challenges are discussed along with recent developments to address these issues. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

  12. Isomerism in benzyl-DOTA derived bifunctional chelators: implications for molecular imaging.

    Science.gov (United States)

    Payne, Katherine M; Woods, Mark

    2015-02-18

    The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd(3+) in particular is of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu(3+) and Yb(3+) chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the [3333] ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd(3+)-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd(3+) chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.

  13. Simultaneous molecular imaging of EGFR and HER2 using hyperspectral darkfield microscopy and immunotargeted nanoparticles

    Science.gov (United States)

    Crow, Matthew J.; Marinakos, Stella; Chilkoti, Ashutosh; Wax, Adam P.

    2009-02-01

    Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) contribute to the regulation of cell proliferation, and when jointly over-expressed are associated with several types of cancer. The ability to monitor both receptors simultaneously results in a more accurate indicator of degree of cancerous activity than either receptor alone. Plasmonic nanoparticles (NPs) show promise as a potential EGFR and HER2 biomarker over alternatives such as fluorophores and quantum dots, which are limited by their cytotoxicity and photobleaching. To observe immunolabeled NPs bound to receptor-expressing cells, our past experiments were conducted using a novel optical darkfield microspectroscopy system. We implemented an epi-illumination darkfield broadband light train, which allows for darkfield analysis of live cells in culture with enhanced NP contrast. Under this setup, molecularly specific binding of NPs immunolabeled with anti-EGFR was confirmed. We have since adapted our darkfield setup, which previously only obtained spectral information from a line imaging spectrometer, to incorporate hyperspectral imaging capabilities, allowing widefield data acquisition within seconds. The new system has been validated through observation of shifts in the peak wavelength of scattering by gold NPs on silanated cover glasses using several immersion media. Peak resonant scattering wavelengths match well with that predicted by Mie theory. We will further demonstrate the potential of the system with simultaneous molecular imaging of multiple receptors in vitro using labeled EGFR+/HER2+ SK-BR-3 human breast cancer cells with anti-EGFR immunolabeled gold nanospheres and anti-HER2 immunolabeled gold nanorods, with each scattering in different spectral windows. Additional trials will be performed to demonstrate molecularly specific binding using EGFR+/HER2- MDA-MB-468 and HER2+/EGFR- MDA-MB-453 breast cancer cells.

  14. Early detection of breast cancer: a molecular optical imaging approach using novel estrogen conjugate fluorescent dye

    Science.gov (United States)

    Bhattacharjee, Shubhadeep; Jose, Iven

    2011-02-01

    Estrogen induced proliferation of mutant cells is widely understood to be the one of major risk determining factor in the development of breast cancer. Hence determination of the Estrogen Receptor[ER] status is of paramount importance if cancer pathogenesis is to be detected and rectified at an early stage. Near Infrared Fluorescence [NIRf] Molecular Optical Imaging is emerging as a powerful tool to monitor bio-molecular changes in living subjects. We discuss pre-clinical results in our efforts to develop an optical imaging diagnostic modality for the early detection of breast cancer. We have successfully carried out the synthesis and characterization of a novel target-specific NIRf dye conjugate aimed at measuring Estrogen Receptor[ER] status. The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of Indocyanine Green (ICG) cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies regarding specific binding and endocytocis of the dye performed on ER+ve [MCF-7] and control [MDA-MB-231] adenocarcinoma breast cancer cell lines clearly indicated nuclear localization of the dye for MCF-7 as compared to plasma level staining for MDA-MB-231. Furthermore, MCF-7 cells showed ~4.5-fold increase in fluorescence signal intensity compared to MDA-MB-231. A 3-D mesh model mimicking the human breast placed in a parallel-plate DOT Scanner is created to examine the in-vivo efficacy of the dye before proceeding with clinical trials. Photon migration and florescence flux intensity is modeled using the finite-element method with the coefficients (quantum yield, molar extinction co-efficient etc.) pertaining to the dye as obtained from photo-physical and in-vitro studies. We conclude by stating that this lipophilic dye can be potentially used as a target specific exogenous contrast agent in molecular optical imaging for early detection of breast cancer.

  15. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel;

    cardiovascular risk factors were prospectively assessed by 18F-FDG (inflammation) and sodium 18F-fluoride (18F-NaF) (molecular calcification) PET CT imaging. Global aortic uptake of 18F-FDG and 18F-NaF was determined semi-quantitatively by calculating the average blood pool corrected standardized uptake value (cSUV......) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...

  16. Peptidyl Molecular Imaging Contrast Agents Using a New Solid Phase Peptide Synthesis Approach

    OpenAIRE

    Yoo, Byunghee; Pagel, Mark D.

    2007-01-01

    A versatile method is disclosed for solid phase peptide synthesis (SPPS) of molecular imaging contrast agents. A DO3A moiety was derivatized to introduce a CBZ-protected amino group and then coupled to a polymeric support. CBZ cleavage with Et2AlCl/thioanisole was optimized for SPPS. Amino acids were then coupled to the aminoDOTA loaded resin using conventional step-wise Fmoc SPPS to create a product with DOTA coupled to the C-terminus of the peptide. In a second study, the DO3A moiety was co...

  17. Pediatric radiological diagnostics in suspected child abuse; Kinderradiologische Diagnostik bei Verdacht auf Kindesmisshandlung

    Energy Technology Data Exchange (ETDEWEB)

    Erfurt, C.; Schmidt, U. [Technische Universitaet Dresden, Institut fuer Rechtsmedizin, Medizinische Fakultaet, Dresden (Germany); Hahn, G. [Universitaetsklinikum Carl Gustav Carus, Dresden, Abteilung Kinderradiologie, Institut und Poliklinik fuer Radiologische Diagnostik, Dresden (Germany); Roesner, D. [Universitaetsklinikum Carl Gustav Carus, Dresden, Klinik und Poliklinik fuer Kinderchirurgie, Dresden (Germany)

    2009-10-15

    Advanced and specialized radiological diagnostics are essential in the case of clinical suspicion of pediatric injuries to the head, thorax, abdomen, and extremities when there is no case history or when ''battered child syndrome'' is assumed on the basis of inadequate trauma. In particular, the aim of this sophisticated diagnostic procedure is the detection of lesions of the central nervous system (CNS) in order to initiate prompt medical treatment. If diagnostic imaging shows typical findings of child abuse, accurate documented evidence of the diagnostic results is required to prevent further endangerment of the child's welfare. (orig.) [German] Klinisch diagnostizierte Verletzungen an Kopf, Thorax, Abdomen oder Extremitaeten eines Kindes bei scheinbar leerer Anamnese oder Angabe eines inadaequaten Traumas erfordern beim Verdacht auf ein Battered-Child-Syndrom eine erweiterte und spezialisierte radiologische Diagnostik. Diese soll insbesondere im Bereich des ZNS Verletzungsfolgen erfassen, um therapeutische Massnahmen einleiten zu koennen. Bei typischen, auf eine Misshandlung hinweisenden radiologischen Befunden ist eine praezise beweissichere Befunddokumentation erforderlich, um eine weitere Kindeswohlgefaehrdung zu vermeiden. (orig.)

  18. Multi-target photoacoustic molecular imaging of cardiovascular inflammatory biomarkers using bioconjugated gold nanorods

    Science.gov (United States)

    Ha, S.; Tripathy, S.; Carson, A.; Lavery, L. L.; Zhang, H.; Agarwal, A.; Kotov, N.; Villanueva, F. S.; Kim, K.

    2011-03-01

    Multiple cardiovascular inflammatory biomarkers were simultaneously imaged in vivo using antibody conjugated gold nanorods (GNRs) injected into a mouse model of vascular injury stimulated by a photochemical reaction of Rose Bengal dye to green light. Mixed solutions of ICAM-1 antibody conjugated GNRs (715 nm) and E-selectin antibody conjugated GNRs (800 nm) were injected to bind to their respective inflammatory markers on the luminal surface of the inferior vena cava of a mouse. Photoacoustic intensity was measured by a commercial ultrasound probe synchronized to a pulsed laser (10-18 mJ/cm2) at 715 nm or 800 nm clearly identified the upregulation of targeted biomarkers. Histopathology on the harvested tissues confirmed inflammation. The feasibility of simultaneous photoacoustic molecular imaging of inflammation responses in cardiovascular system using a commercial ultrasound system has been demonstrated in vivo.

  19. Universal Molecular Scaffold for Facile Construction of Multivalent and Multimodal Imaging Probes.

    Science.gov (United States)

    Gai, Yongkang; Xiang, Guangya; Ma, Xiang; Hui, Wenqi; Ouyang, Qin; Sun, Lingyi; Ding, Jiule; Sheng, Jing; Zeng, Dexing

    2016-03-16

    Multivalent and multimodal imaging probes are rapidly emerging as powerful chemical tools for visualizing various biochemical processes. Herein, we described a bifunctional chelator (BFC)-based scaffold that can be used to construct such promising probes concisely. Compared to other reported similar scaffolds, this new BFC scaffold demonstrated two major advantages: (1) significantly simplified synthesis due to the use of this new BFC that can serve as chelator and linker simultaneously; (2) highly efficient synthesis rendered by using either click chemistry and/or total solid-phase synthesis. In addition, the versatile utility of this molecular scaffold has been demonstrated by constructing several multivalent/multimodal imaging probes labeled with various radioisotopes, and the resulting radiotracers demonstrated substantially improved in vivo performance compared to the two individual monomeric counterparts.

  20. In-vivo human brain molecular imaging with a brain-dedicated PET/MRI system.

    Science.gov (United States)

    Cho, Zang Hee; Son, Young Don; Choi, Eun Jung; Kim, Hang Keun; Kim, Jeong Hee; Lee, Sang Yoon; Ogawa, Seiji; Kim, Young Bo

    2013-02-01

    Advances in the new-generation of ultra-high-resolution, brain-dedicated positron emission tomography-magnetic resonance imaging (PET/MRI) systems have begun to provide many interesting insights into the molecular dynamics of the brain. First, the finely delineated structural information from ultra-high-field MRI can help us to identify accurate landmark structures, thereby making it easier to locate PET activation sites that are anatomically well-correlated with metabolic or ligand-specific organs in the neural structures in the brain. This synergistic potential of PET/MRI imaging is discussed in terms of neuroscience and neurological research from both translational and basic research perspectives. Experimental results from the hippocampus, thalamus, and brainstem obtained with (18)F-fluorodeoxyglucose and (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile are used to demonstrate the potential of this new brain PET/MRI system.

  1. Super-Resolution Molecular and Functional Imaging of Nanoscale Architectures in Life and Materials Science

    KAUST Repository

    Habuchi, Satoshi

    2014-06-12

    Super-resolution (SR) fluorescence microscopy has been revolutionizing the way in which we investigate the structures, dynamics, and functions of a wide range of nanoscale systems. In this review, I describe the current state of various SR fluorescence microscopy techniques along with the latest developments of fluorophores and labeling for the SR microscopy. I discuss the applications of SR microscopy in the fields of life science and materials science with a special emphasis on quantitative molecular imaging and nanoscale functional imaging. These studies open new opportunities for unraveling the physical, chemical, and optical properties of a wide range of nanoscale architectures together with their nanostructures and will enable the development of new (bio-)nanotechnology.

  2. The use of anatomical information for molecular image reconstruction algorithms: Attention/Scatter correction, motion compensation, and noise reduction

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Se Young [School of Electrical and Computer Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan (Korea, Republic of)

    2016-03-15

    PET and SPECT are important tools for providing valuable molecular information about patients to clinicians. Advances in nuclear medicine hardware technologies and statistical image reconstruction algorithms enabled significantly improved image quality. Sequentially or simultaneously acquired anatomical images such as CT and MRI from hybrid scanners are also important ingredients for improving the image quality of PET or SPECT further. High-quality anatomical information has been used and investigated for attenuation and scatter corrections, motion compensation, and noise reduction via post-reconstruction filtering and regularization in inverse problems. In this article, we will review works using anatomical information for molecular image reconstruction algorithms for better image quality by describing mathematical models, discussing sources of anatomical information for different cases, and showing some examples.

  3. The Use of Anatomical Information for Molecular Image Reconstruction Algorithms: Attenuation/Scatter Correction, Motion Compensation, and Noise Reduction.

    Science.gov (United States)

    Chun, Se Young

    2016-03-01

    PET and SPECT are important tools for providing valuable molecular information about patients to clinicians. Advances in nuclear medicine hardware technologies and statistical image reconstruction algorithms enabled significantly improved image quality. Sequentially or simultaneously acquired anatomical images such as CT and MRI from hybrid scanners are also important ingredients for improving the image quality of PET or SPECT further. High-quality anatomical information has been used and investigated for attenuation and scatter corrections, motion compensation, and noise reduction via post-reconstruction filtering and regularization in inverse problems. In this article, we will review works using anatomical information for molecular image reconstruction algorithms for better image quality by describing mathematical models, discussing sources of anatomical information for different cases, and showing some examples. PMID:26941855

  4. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

    Science.gov (United States)

    Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

    2006-11-01

    In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

  5. Exploration of target molecules for molecular imaging of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan); Enomoto, Shuichi, E-mail: senomoto@pharm.okayama-u.ac.jp [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)

    2011-07-08

    Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In

  6. Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images; Radiofarmacos: nanoparticulas como sistemas multifuncionales para la obtencion in vivo de imagenes moleculares

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N., E-mail: guillermina.ferro@inin.gob.m [ININ, Departamento de Materiales Radiactivos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

  7. Sodium Iodide Symporter for Nuclear Molecular Imaging and Gene Therapy: From Bedside to Bench and Back

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn

    2012-01-01

    Full Text Available Molecular imaging, defined as the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms, can be obtained by various imaging technologies, including nuclear imaging methods. Imaging of normal thyroid tissue and differentiated thyroid cancer, and treatment of thyroid cancer with radioiodine rely on the expression of the sodium iodide symporter (NIS in these cells. NIS is an intrinsic membrane protein with 13 transmembrane domains and it takes up iodide into the cytosol from the extracellular fluid. By transferring NIS function to various cells via gene transfer, the cells can be visualized with gamma or positron emitting radioisotopes such as Tc-99m, I-123, I-131, I-124 and F-18 tetrafluoroborate, which are accumulated by NIS. They can also be treated with beta- or alpha-emitting radionuclides, such as I-131, Re-186, Re-188 and At-211, which are also accumulated by NIS. This article demonstrates the diagnostic and therapeutic applications of NIS as a radionuclide-based reporter gene for trafficking cells and a therapeutic gene for treating cancers.

  8. Farbe bekennen – Grüne Bibliotheken auf die Tagesordnung! Vortrag auf dem 103. Deutschen Bibliothekartag, Bremen, 5. Juni 2014

    Directory of Open Access Journals (Sweden)

    Petra Hauke

    2014-12-01

    Full Text Available Was in vielen Ländern bereits im Alltag der Bibliotheken verankert ist, beginnt in Deutschland erst sehr zaghaft: Das Verantwortungsbewusstsein von Bibliotheken für die ökologische Bildung der Gesellschaft und die Konsequenzen daraus für die Bibliothekspraxis. Es ist höchste Zeit, in der deutschen Bibliothekslandschaft publik zu machen, was eine „Grüne Bibliothek“ sein kann – bezogen auf das Gebäude, die Ausstattung, das Management, die Services für die Nutzer. Anhand einer Checkliste wird gezeigt, wie Bibliotheken mit einem „grünen“ Konzept nicht nur selbst etwas für die ökologische Nachhaltigkeit tun können, sondern auch wie sie als Multiplikatoren in den Kommunen, Hochschulen und bei anderen Trägern Einfluss auf das ökologische Verhalten nehmen und damit einen wichtigen Beitrag für unsere Gesellschaft leisten. Bringing environmental awareness to libraries does not necessarily imply huge financial efforts or a big budget. Ecological sustainability is an undervalued aspect of the marketing strategy for libraries which has more impact on clients and on stakeholders than one would expect. Small steps in going green can make a big impact for the library’s image. Little financial input can produce an important marketing outcome. Activities in this field can be developed in cooperation with unpaid partners like non-governmental organisations (NGOs, Friends of the Library groups, library suppliers and, last but not least, the library users. A checklist on how to go green gives an overview of important aspects in planning, construction, and library operations in order to introduce the first “green footsteps”.

  9. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    Science.gov (United States)

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  10. High Resolution Imaging of Defect Structures in Polymer and Organic Molecular Crystals

    Science.gov (United States)

    Martin, David

    2003-03-01

    We have been developing techniques for the low dose High Resolution Electron Microscopy (HREM) imaging of defect structures in polymer and organic molecular crystals. We have examined a variety of technologically important materials systems including rigid-rod polymers, poly(imides), poly(diacetylenes), poly(bisthiazoles), poly(bisoxazoles), and aromatic polyamides such as poly(paraphenylene terephthalamide) (PPTA or Kevlar(R)) and poly(metaphenylene diisophthalamide) (MPDI or Nomex(R)). These studies have made it possible for us to image the molecular reorganization in the vicinity of dislocations, surfaces, and grain boundaries. We have also learned about the micromechanisms of lattice bending and twisting. Most recently we have been examining the microstructure of pentacene, a highly-crystalline conjugated organic small molecule that is of interest for making flexible electronic devices such as thin-film transistors. We have also been examing the utility of low voltage techniques using a table-top sized electron microscope that operates near 5 kV.

  11. Molecular orbital imaging of cobalt phthalocyanine on native oxidized copper layers using STM

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Qinmin; Huang, Min; Qin, Zhihui [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Xiaohongshan West 30, Wuchang, Wuhan 430071 (China); Cao, Gengyu, E-mail: gycao@wipm.ac.cn [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Xiaohongshan West 30, Wuchang, Wuhan 430071 (China)

    2012-07-15

    To observe molecular orbitals using scanning tunneling microscopy, well-ordered oxidized layers on Cu(001) were fabricated to screen the individual adsorbed cobalt phthalocyanine (CoPc) molecules from the electronic influence of the metal surface. Scanning tunneling microscope images of the molecule on this oxidized layer show similarities to the orbital distribution of the free molecule. The good match between the differential conductance mapping images and the calculated charge distribution at energy levels corresponding to the frontier orbitals of CoPc provides more evidence of the screening of the oxidized layer from interactions between the metal surface and supported molecules. -- Highlights: Black-Right-Pointing-Pointer STM is a powerful tool to depict molecular orbitals, a basic concept of chemistry. Black-Right-Pointing-Pointer Native copper oxide layer was fabricated for adsorption of cobalt phthalocyanine. Black-Right-Pointing-Pointer Detailed orbitals of CoPc were successfully observed for the 1st time by STM. Black-Right-Pointing-Pointer The effect of the layer is explained by DFT quantum mechanical computations.

  12. Molecular orbital imaging of cobalt phthalocyanine on native oxidized copper layers using STM

    International Nuclear Information System (INIS)

    To observe molecular orbitals using scanning tunneling microscopy, well-ordered oxidized layers on Cu(001) were fabricated to screen the individual adsorbed cobalt phthalocyanine (CoPc) molecules from the electronic influence of the metal surface. Scanning tunneling microscope images of the molecule on this oxidized layer show similarities to the orbital distribution of the free molecule. The good match between the differential conductance mapping images and the calculated charge distribution at energy levels corresponding to the frontier orbitals of CoPc provides more evidence of the screening of the oxidized layer from interactions between the metal surface and supported molecules. -- Highlights: ► STM is a powerful tool to depict molecular orbitals, a basic concept of chemistry. ► Native copper oxide layer was fabricated for adsorption of cobalt phthalocyanine. ► Detailed orbitals of CoPc were successfully observed for the 1st time by STM. ► The effect of the layer is explained by DFT quantum mechanical computations.

  13. Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

    Directory of Open Access Journals (Sweden)

    Eugene Gu, Wen-Yi Chen, Jay Gu, Paul Burridge, Joseph C. Wu

    2012-01-01

    Full Text Available Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

  14. Image-charge-induced localization of molecular orbitals at metal-molecule interfaces

    DEFF Research Database (Denmark)

    Strange, M.; Thygesen, K. S.

    2012-01-01

    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-conjugat......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......-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...... 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 and...

  15. A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Cusanno, F., E-mail: francesco.cusanno@iss.infn.i [I.N.F.N., Gruppo Collegato Sanita, Sezione di Roma, Rome (Italy); Istituto Superiore di Sanita, Rome (Italy); Argentieri, A. [I.N.F.N., Sezione di Bari, Bari (Italy); Baiocchi, M.; Colilli, S.; Cisbani, E. [Istituto Superiore di Sanita, Rome (Italy); De Vincentis, G. [Universita La Sapienza, Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita, Rome (Italy); Garibaldi, F. [I.N.F.N., Gruppo Collegato Sanita, Sezione di Roma, Rome (Italy); Giuliani, F.; Gricia, M.; Lucentini, M. [Istituto Superiore di Sanita, Rome (Italy); Magliozzi, M.L. [I.N.F.N., Gruppo Collegato Sanita, Sezione di Roma, Rome (Italy); Istituto Superiore di Sanita, Rome (Italy); Majewski, S. [West Virginia University, Morgantown WV (United States); Marano, G. [Istituto Superiore di Sanita, Rome (Italy); Musico, P. [I.N.F.N., Sezione di Genova, Genoa (Italy); Musumeci, M.; Santavenere, F.; Torrioli, S. [Istituto Superiore di Sanita, Rome (Italy); Tsui, B.M.W. [Johns Hopkins University, Baltimore MD (United States); Vitelli, L. [Istituto Superiore di Sanita, Rome (Italy)

    2010-05-21

    Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr{sub 3}(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr{sub 3}(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

  16. Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications

    Science.gov (United States)

    Glaser, Adam K.; Zhang, Rongxiao; Andreozzi, Jacqueline; Gladstone, David; Pogue, Brian

    2016-03-01

    Cherenkov radiation has emerged as a novel source of light with a number of applications in the biomedical sciences. It's unique properties, including its broadband emission spectrum, spectral weighting in the ultraviolet and blue wavebands, and local generation of light within a given tissue have made it an attractive source of light for techniques ranging from widefield imaging to oximetry and phototherapy. To help guide the future development of this field in the context of molecular imaging, quantitative estimates of the light fluence rates of Cherenkov radiation from a number of radionuclide and external radiotherapy beams in tissue was explored for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.1 - 1 nW/cm2 per MBq/g for radionuclides and 1 - 10 μW/cm2 per Gy/sec for external radiotherapy beams, dependent on the given waveband and optical properties. For phototherapy applications, the total light fluence was found to be on the order of nJ/cm2 for radionuclides, and mJ/cm2 for radiotherapy beams. To validate these findings, experimental validation was completed with an MV x-ray photon beam incident onto a tissue phantom, confirming the magnitudes of the simulation values. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at these relatively low fluence values.

  17. 124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Giuseppe Lucio Cascini

    2014-01-01

    Full Text Available 124Iodine (124I with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

  18. Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status.

    Science.gov (United States)

    Pais, Adi; Degani, Hadassa

    2016-01-01

    The estrogen receptor (ER) α is overexpressed in most breast cancers, and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) effects of two novel ER-targeted contrast agents (CAs), based on pyridine-tetra-acetate-Gd(III) chelate conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd). The experiments were conducted in solution, in human breast cancer cells, and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen-like agonistic activity, enhancing cell proliferation, as well as upregulating cMyc oncogene and downregulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast-enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd-specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors' ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also revealed that this

  19. Estrogen receptor targeted contrast agents for molecular magnetic resonance imaging of breast cancer hormonal status

    Directory of Open Access Journals (Sweden)

    Adi ePais

    2016-04-01

    Full Text Available The estrogen receptor α (ER is over expressed in most breast cancers and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer, as well as in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging effects of two novel ER- targeted contrast agents (CAs based on pyridine-tetra-acetate-Gd(III chelate conjugated to 17β-estradiol (EPTA-Gd or to tamoxifen (TPTA-Gd. The experiments were conducted in solution, in human breast cancer cells and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen like agonistic activity, enhancing cell proliferation, as well as up-regulating cMyc oncogene and down-regulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors’ ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also

  20. Molecular imaging in patients with mood disorders: a review of PET findings

    International Nuclear Information System (INIS)

    Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

  1. Auf den Schultern von Riesen und Zwergen Einsteins unvollendete Revolution

    CERN Document Server

    Renn, Jürgen

    2006-01-01

    Dies ist die Geschichte von Einsteins unvollendeter Revolution, einer tiefgreifenden Veränderung unserer Begriffe von Raum, Zeit, Materie und Strahlung. Diese Revolution begann in Einsteins Wunderjahr 1905, wurde durch seine allgemeine Relativitätstheorie aus dem Jahre 1915 fortgesetzt und wirkt in den heutigen Versuchen der Wissenschaft, die Entstehung und das Schicksal des Universums zu verstehen, weiter. Vor dem Hintergrund einer historischen Theorie des wissenschaftlichen Fortschritts wird Einsteins bis heute nicht abgeschlossene Revolution als das Ergebnis einer langfristigen Entwicklung des Wissens verständlich. Anhand der spannenden Geschichte von Einsteins Entdeckungen wird nachvollziehbar, warum große Denker wie Einstein weiter gesehen haben als ihre Vorgänger. Sie standen nicht nur auf den Schultern von Riesen, also den wissenschaftlichen Leistungen einzelner großer Vorgänger wie Newton, sondern auch auf den Schultern von "Zwergen", dem wissenschaftlichen Wissen, dem technischen Wissen, und d...

  2. Metal-Based Systems for Molecular Imaging Applications - COST D38 Annual Workshop - Scientific Program and Abstracts

    International Nuclear Information System (INIS)

    The main objective of the Action is the development of metal-based imaging probes for cellular and molecular imaging applications, based on MRI, PET, SPECT and optical imaging that will facilitate early diagnosis, assessment of disease progression and treatment evaluation.The goal of this Action is to further the development of innovative imaging probes through the pursuit of innovations in a number of different areas, ranging from the design of imaging units endowed with enhanced sensitivity to the control of the structural and electronic determinants responsible for the molecular recognition of the target molecule.At present, in vivo diagnostic systems basically assess the structure and function of human organs. Therefore, for important diseases such as cancer and cardiovascular pathologies,and also diseases of the central nervous system, only the late symptoms are detected. It is expected that the advances in genomics and proteomics will have a tremendous impact on human health care of the future. However, advances in molecular biology are already redefining diseases in terms of molecular abnormalities. With this knowledge, new generations of diagnostic imaging agents can be defined that aim at the detection of those molecular processes in vivo.The molecular imaging approach offers a great potential for earlier detection and characterisation of disease, and evaluation of treatment. However, more research is necessary to bring these ideas to clinical applications and a key aspect relates to the development of high-specificity, high-sensitivity imaging probes for the different detection modalities. Additionally, the Action includes research activities dealing with the exploitation of peculiar nuclear properties of given isotopes for therapeutic effects, thus integrating the diagnostic and the therapeutic stages.Apart from its use in early diagnosis in clinical practice, the molecular imaging approach will have also a major impact on the development of new

  3. The Use of Radiation Detectors in Medicine: The Future of Molecular Imaging and Multimodality Imaging: Advantages and Technological Challenges (3/3)

    CERN Document Server

    CERN. Geneva

    2009-01-01

    The development of radiation detectors in the field of nuclear and particle physics has had a terrific impact in medical imaging since this latter discipline took off in late ’70 with the invention of the CT scanners. The massive use in High Energy Physics of position sensitive gas detectors, of high Z and high density scintillators coupled to Photomultiplier (PMT) and Position Sensitive Photomultipliers (PSPMT), and of solid state detectors has triggered during the last 30 years a series of novel applications in Medical Imaging with ionizing radiation. The accelerated scientific progression in genetics and molecular biology has finally generated what it is now called Molecular Imaging. This field of research presents additional challenges not only in the technology of radiation detector, but more and more in the ASIC electronics, fast digital readout and parallel software. In this series of three lectures I will try to present how high energy physics and medical imaging development have both benefited by t...

  4. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    Science.gov (United States)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  5. Der Einfluss von Relaxin auf das Wachstum von Mammakarzinomen

    OpenAIRE

    Habla, Christiane

    2010-01-01

    Brustkrebs ist die häufigste Krebstodesursache bei Frauen in den Industrienationen mit einer jährlich ansteigenden Neuerkrankungsrate (Senn und Niederberger 2002). Durch vorangegangene Untersuchungen wurde bereits deutlich, dass das Peptidhormon Relaxin unter in vitro Bedingungen maßgeblich zur Tumorprogression von Mammakarzinomen beiträgt (Binder et al. 2002). Die vorliegende Arbeit hat untersucht, ob Relaxin diese Wirkung auch in vivo auf Mammakarzinome ausübt. Relaxin ist...

  6. Textile Betonbewehrungen auf Basis der Multiaxial-Kettenwirktechnik

    OpenAIRE

    Cherif, Chokri; Hausding, Jan; Berger, Ulrike; Younes, Ayham; Kleicke, Roland

    2011-01-01

    Dieser Beitrag bietet einen Überblick über die in zwölf Jahren Forschungsarbeit am Institut für Textilmaschinen und Textile Hochleistungswerkstofftechnik (ITM) erzielten Ergebnisse auf dem Gebiet textiler Betonbewehrungen unter Einsatz der Nähwirktechnik. Standen zunächst die Weiterentwicklung der Nähwirk- bzw. Multiaxial-Kettenwirktechnik und die Integration zusätzlicher Prozessschritte im Mittelpunkt, so wurde dies mit der Einführung neuer Faserwerkstoffe durch die Beantwortung grundlegende...

  7. Adsorption von Phthalocyaninen auf Edelmetalloberflächen

    OpenAIRE

    Kröger, I.

    2011-01-01

    Die Untersuchungen der physikalischen Eigenschaften großer π-konjugierter Moleküle, deren Wechselwirkung untereinander und die Adsorption auf metallischen Oberflächen sind ein Schwerpunktthema in der aktuellen Forschung der Oberflächenphysik. Durch ihre ausserordentliche Vielfältigkeit stellen Moleküle vielversprechende Materialien für optische und elektronische Bauelemente (organische Leuchtdioden, organisches Feldeffekttransistoren, organische Solarzellen) dar und finden bereits in...

  8. Wie reagieren Hochschulen auf neue Technologien? Das Beispiel der Photovoltaik

    OpenAIRE

    Franz, Peter

    2008-01-01

    Hochschulen kommt als Akteuren in regionalen Innovationssystemen die Aufgabe zu, neues Wissen für eine Region verfügbar zu machen, durch Lehre zur Humankapitalbildung und durch Forschung zur Erweiterung des Wissens beizutragen. Diese Funktionen sind insbesondere wichtig bei der Adaption neuer Technologien, wie dies bei der Photovoltaik der Fall ist. 89 deutsche Hochschulen – darunter 65 Fachhochschulen – bieten mittlerweile 171 Vollzeitstudiengänge mit Ausrichtung auf die Photovoltaik an. Jed...

  9. Staatsverschuldung: Privilegien des Staates auf dem Prüfstand

    OpenAIRE

    Büttner, Thiess; Konrad, Kai A.; Rocholl, Jörg

    2014-01-01

    Der wissenschaftliche Beirat beim Bundesfinanzministerium hat jüngst in einer Stellungnahme darauf aufmerksam gemacht, dass die gegenwärtige Finanzordnung in der Europäischen Währungsunion dem Staat in seiner Eigenschaft als Schuldner besondere Privilegien einräumt. Die Autoren geben einen kurzen Überblick über diese Privilegien, diskutieren die daraus resultierenden Probleme und zeigen die Notwendigkeit ihres Abbaus auf. Even though governments usually enjoy favourable borrowing condition...

  10. Einfluss des Pneumoperitoneums auf die Ultrastruktur des Peritoneums

    OpenAIRE

    Jakob, Jens

    2004-01-01

    Hintergrund: Der Einsatz minimal invasiver Techniken in der onkologischen Chirurgie wird wegen der Berichte über Trokarmetastasen kontrovers diskutiert. Die Pathogenese von Inzisionsmetastasen und intraperitonealem Tumorwachstum ist bisher nicht bekannt. Als mögliche Ursachen kommen bei Einsatz der laparoskopischen Chirurgie auch Einflüsse von Gas und Druck auf das Peritoneum in Betracht. Dabei könnte eine peritoneale Inflammation die Adhäsion und das Wachstum von Tumorzellen begünstigen. Wir...

  11. Auswirkungen von Mehrfachmandaten deutscher Vorstands- und Aufsichtsratsvorsitzender auf den Unternehmenserfolg

    OpenAIRE

    Balsmeier, Benjamin; Buchwald, Achim; Peters, Heiko

    2010-01-01

    Mehrfachmandatsträger in Vorständen und Aufsichtsräten stehen seit langer Zeit in der öffentlichen Kritik. Anhand eines Paneldatensatzes für die größten deutschen Unternehmen im Zeitraum von 1996 bis 2006 wird der Einfluss von Mehrfachmandaten von Vorstands- und Aufsichtsratsvorsitzenden auf den Unternehmenserfolg untersucht. Die Ergebnisse legen den Schluss nahe, dass zwischen der Anzahl der Aufsichtsratsmandate des Vorstandsvorsitzenden und dem Erfolg seines Unternehmens ein konkaver positi...

  12. Einfluss der approximalen Kastenelevationstechnik auf die marginale Adaptation von Keramikinlays

    OpenAIRE

    Hehn, Julia

    2012-01-01

    1. Hintergrund und Ziele Auf Grund der schmelzähnlichen Eigenschaften, einer hohen Biokompatibilität und der ästhetisch anspruchsvollen Optik werden heute bevorzugt vollkeramische Werkstoffe als Inlaymaterial verwendet. Wie Langzeitstudien belegen, können auch weit extendierte Kavitäten erfolgreich mit Keramik versorgt werden. Die indirekte Versorgung tiefreichender Defekte bis apikal der Schmelz-Zement-Grenze gestaltet sich jedoch sehr arbeits- und zeitintensiv. Ziel der vorliegenden Studie ...

  13. Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography.

    Science.gov (United States)

    Lambers, F M; Stuker, F; Weigt, C; Kuhn, G; Koch, K; Schulte, F A; Ripoll, J; Rudin, M; Müller, R

    2013-02-01

    Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, pbone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (pBone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.

  14. Molecular Origin of Color Variation in Firefly (Beetle) Bioluminescence: A Chemical Basis for Biological Imaging.

    Science.gov (United States)

    Hirano, Takashi

    2016-01-01

    Firefly shows bioluminescence by "luciferin-luciferase" (L-L) reaction using luciferin, luciferase, ATP and O2. The chemical photon generation by an enzymatic reaction is widely utilized for analytical methods including biological imaging in the life science fields. To expand photondetecting analyses with firefly bioluminescence, it is important for users to understand the chemical basis of the L-L reaction. In particular, the emission color variation of the L-L reaction is one of the distinguishing characteristics for multicolor luciferase assay and in vivo imaging. From the viewpoint of fundamental chemistry, this review explains the recent progress in the studies on the molecular mechanism of emission color variation after showing the outline of the reaction mechanism of the whole L-L reaction. On the basis of the mechanism, the progresses in organic synthesis of luciferin analogs modulating their emission colors are also presented to support further developments of red/near infrared in vivo biological imaging utility of firefly bioluminescence.

  15. Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

    Directory of Open Access Journals (Sweden)

    Moritz Palmowski

    2009-09-01

    Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

  16. DISENTANGLING THE CIRCUMNUCLEAR ENVIRONS OF CENTAURUS A. I. HIGH-RESOLUTION MOLECULAR GAS IMAGING

    International Nuclear Information System (INIS)

    We present high-resolution images of the 12CO(2-1) emission in the central 1' (1 kpc) of NGC 5128 (Centaurus A), observed using the Submillimeter Array. We elucidate for the first time the distribution and kinematics of the molecular gas in this region with a resolution of 6.''0 x 2.''4 (100 pc x 40 pc). We spatially resolve the circumnuclear molecular gas in the inner 24''x 12'' (400 pc x 200 pc), which is elongated along a position angle of P.A. ≅155 deg. and perpendicular to the radio/X-ray jet. The southeast (SE) and northwest (NW) components of the circumnuclear gas are connected to molecular gas found at larger radii. This gas appears as two parallel filaments at P.A. = 120 deg., which are coextensive with the long sides of the 3 kpc parallelogram shape of the previously observed dust continuum, as well as ionized and pure rotational H2 lines. Spatial and kinematical asymmetries are apparent in both the circumnuclear and outer gas, suggesting noncoplanar and/or noncircular motions. We extend to inner radii (r12CO(2 - 1) observations show relevant deviations from this model: namely, the physical connection between the circumnuclear gas and that at larger radii, brighter SE and NW sides on the parallelogram-shaped feature, and an outer curvature of its long sides. Overall, it resembles more closely an S-shaped morphology, a trend that is also found in other molecular species. Hence, we qualitatively explore the possible contribution of a weak bi-symmetric potential which would naturally explain these peculiarities.

  17. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  18. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUVmax; SUVmean) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R2. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUVmean (P=.018), and midtreatment FLT SUVmax (P=.006). Large decreases in FLT SUVmean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUVmax (P=.022) in combination with large FLT response from

  19. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 99m}Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for {sup 99m}Tc-HYNlC-TOC and {sup 188}Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after {sup 99m}Tc-HYNlC-TOC or {sup 188}Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. {sup 99m}Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 {+-} 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of {sup 188}Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  20. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

    OpenAIRE

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the ...

  1. Novel high resolution SPECT instrumentation and techniques for molecular imaging of small animals

    International Nuclear Information System (INIS)

    The main purpose of the project is the development and tuning of an advanced detector system for molecular imaging with radionuclides on small animal. The equipment has sub-millimeter spatial resolution, adequate sensitivity and field of view, It is designed for studies, on animal models, of diagnostic and/or therapeutic techniques in cardiovascular diseases, such as detection and identification of vulnerable plaques in atherosclerosis and stem cell therapy for cardiac repair. The present activities is carried on in collaboration with groups from Johns Hopkins University (Baltimore), Jefferson Lab (Newport News), Istituto Nazionale Fisica Nucleare (INFN) and ISS (Dept. Technology and Health and Dept. Therapeutic Research and Medicines Evaluation). The main results of the last two years are summarized as follows: development of the SPECT system prototype; set up of the technique for vulnerable plaques detection;demonstration of detectability of the cardiac perfusion via peritoneum injection of the radiotracer

  2. Electron spin resonance studies on reduction process of nitroxyl spin radicals used in molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Dhas, M. Kumara; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com [Department of Physics, NMSSVN College, Nagamalai, Madurai-625019, Tamilnadu (India); Jawahar, A. [Department of Chemistry, NMSSVN College, Nagamalai, Madurai-625019, Tamilnadu (India)

    2014-04-24

    The Electron spin resonance studies on the reduction process of nitroxyl spin probes were carried out for 1mM {sup 14}N labeled nitroxyl radicals in pure water and 1 mM concentration of ascorbic acid as a function of time. The electron spin resonance parameters such as signal intensity ratio, line width, g-value, hyperfine coupling constant and rotational correlation time were determined. The half life time was estimated for 1mM {sup 14}N labeled nitroxyl radicals in 1 mM concentration of ascorbic acid. The ESR study reveals that the TEMPONE has narrowest line width and fast tumbling motion compared with TEMPO and TEMPOL. From the results, TEMPONE has long half life time and high stability compared with TEMPO and TEMPOL radical. Therefore, this study reveals that the TEMPONE radical can act as a good redox sensitive spin probe for molecular imaging.

  3. Nonlinear contrast enhancement in photoacoustic molecular imaging with gold nanosphere encapsulated nanoemulsions

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Chen-wei; Lombardo, Michael; Larson-Smith, Kjersta; Perez, Camilo; Xia, Jinjun; Matula, Thomas; Pozzo, Danilo; O' Donnell, Matthew [Departments of Bioengineering and Chemical Engineering, and Applied Physics Lab, University of Washington, Seattle, Washington 98195 (United States); Pelivanov, Ivan [Departments of Bioengineering and Chemical Engineering, and Applied Physics Lab, University of Washington, Seattle, Washington 98195 (United States); International Laser Center, Moscow State University, Moscow (Russian Federation)

    2014-01-20

    A composite contrast agent, a nanoemulsion bead with assembled gold nanospheres at the interface, is proposed to improve the specific contrast of photoacoustic molecular imaging. A phase transition in the bead's core is induced by absorption of a nanosecond laser pulse with a fairly low laser fluence (∼3.5 mJ/cm{sup 2}), creating a transient microbubble through dramatically enhanced thermal expansion. This generates nonlinear photoacoustic signals with more than 10 times larger amplitude compared to that of a linear agent with the same optical absorption. By applying a differential scheme similar to ultrasound pulse inversion, more than 40 dB contrast enhancement is demonstrated with suppression of background signals.

  4. Molecular imaging with radionuclides, a powerful technique for studying biological processes in vivo

    Science.gov (United States)

    Cisbani, E.; Cusanno, F.; Garibaldi, F.; Magliozzi, M. L.; Majewski, S.; Torrioli, S.; Tsui, B. M. W.

    2007-02-01

    Our team is carrying on a systematic study devoted to the design of a SPECT detector with submillimeter resolution and adequate sensitivity (1 cps/kBq). Such system will be used for functional imaging of biological processes at molecular level in small animal. The system requirements have been defined by two relevant applications: study of atherosclerotic plaques characterization and stem cells diffusion and homing. In order to minimize costs and implementation time, the gamma detector will be based—as much as possible—on conventional components: scintillator crystal and position sensitive PhotoMultipliers read by individual channel electronics. A coded aperture collimator should be adapted to maximize the efficiency. The optimal selection of the detector components is investigated by systematic use of Monte-Carlo simulations (and laboratory validation tests); and finally preliminary results are presented and discussed here.

  5. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias

    Tumor hypoxia is one of the key factors in the development of aggressive and treatment resistant tumors. The negative effects of tumor hypoxia are mediated both by the direct lack of molecular oxygen for therapeutic efficacy and by pro- teomic and genomic changes induced in hypoxic tumor cells....... Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... the potential of implementing canine cancer patients in translational research on tumor hypoxia. 2) Non- invasively evaluate the hypoxia positron emission tomography (PET) tracer 64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including the comparison to non-invasive measures of tumor...

  6. Electron spin resonance studies on reduction process of nitroxyl spin radicals used in molecular imaging

    International Nuclear Information System (INIS)

    The Electron spin resonance studies on the reduction process of nitroxyl spin probes were carried out for 1mM 14N labeled nitroxyl radicals in pure water and 1 mM concentration of ascorbic acid as a function of time. The electron spin resonance parameters such as signal intensity ratio, line width, g-value, hyperfine coupling constant and rotational correlation time were determined. The half life time was estimated for 1mM 14N labeled nitroxyl radicals in 1 mM concentration of ascorbic acid. The ESR study reveals that the TEMPONE has narrowest line width and fast tumbling motion compared with TEMPO and TEMPOL. From the results, TEMPONE has long half life time and high stability compared with TEMPO and TEMPOL radical. Therefore, this study reveals that the TEMPONE radical can act as a good redox sensitive spin probe for molecular imaging

  7. Collimator design for a dedicated molecular breast imaging-guided biopsy system: Proof-of-concept

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; Conners, Amy L.; O' Connor, Michael K. [Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (United States)

    2013-01-15

    Purpose: Molecular breast imaging (MBI) is a dedicated nuclear medicine breast imaging modality that employs dual-head cadmium zinc telluride (CZT) gamma cameras to functionally detect breast cancer. MBI has been shown to detect breast cancers otherwise occult on mammography and ultrasound. Currently, a MBI-guided biopsy system does not exist to biopsy such lesions. Our objective was to consider the utility of a novel conical slant-hole (CSH) collimator for rapid (<1 min) and accurate monitoring of lesion position to serve as part of a MBI-guided biopsy system. Methods: An initial CSH collimator design was derived from the dimensions of a parallel-hole collimator optimized for MBI performed with dual-head CZT gamma cameras. The parameters of the CSH collimator included the collimator height, cone slant angle, thickness of septa and cones of the collimator, and the annular areas exposed at the base of the cones. These parameters were varied within the geometric constraints of the MBI system to create several potential CSH collimator designs. The CSH collimator designs were evaluated using Monte Carlo simulations. The model included a breast compressed to a thickness of 6 cm with a 1-cm diameter lesion located 3 cm from the collimator face. The number of particles simulated was chosen to represent the count density of a low-dose, screening MBI study acquired with the parallel-hole collimator for 10 min after a {approx}150 MBq (4 mCi) injection of Tc-99m sestamibi. The same number of particles was used for the CSH collimator simulations. In the resulting simulated images, the count sensitivity, spatial resolution, and accuracy of the lesion depth determined from the lesion profile width were evaluated. Results: The CSH collimator design with default parameters derived from the optimal parallel-hole collimator provided 1-min images with error in the lesion depth estimation of 1.1 {+-} 0.7 mm and over 21 times the lesion count sensitivity relative to 1-min images

  8. PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [18F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [18F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [18F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [18F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [18F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [18F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author)

  9. Entwicklung eines Entwurfsverfahrens für Schiffsruder auf der Basis statistischer Betriebsprofile

    OpenAIRE

    Greitsch, Lars

    2011-01-01

    Anhand des untersuchten Beispielschiffs wird deutlich, dass die Definition des Entwurfspunktes, auf den sich üblicherweise alle Entwurfs- und Optimierungsstrategien fokussieren, sich im späteren Betriebsalltag im Vergleich zum auftretenden mittleren Betriebszustand nicht bestätigt. Damit weichen auch die aus dem Entwurfszustand abgeleiteten Annahmen in ähnlicher Weise von der Realität ab. Die auf dieser Basis erstellte Entwurfsvariante ist wie belegt im Hinblick auf den späteren Betrieb subop...

  10. Erhebung zur wesensgemäßen Haltung von Schweinen auf Demeter-Betrieben

    OpenAIRE

    Pötzsch, Johanna; Hörning, Bernhard; Hoffmann, Heide

    2015-01-01

    Ziel der Untersuchung war ein Einblick in die Schweinehaltung auf Demeter-Betrieben in Deutschland. Es wurden Vor-Ort-Interviews auf 19 Betrieben in 5 Regionen durchgeführt. Insgesamt wurden auf den Betrieben ca. 200 Sauen und 2.000 Mastschweine gehalten. Demzufolge hatte die Schweinehaltung einen relativ geringen Stellenwert. Viele Betriebe hielten alte Rassen und fütterten verschiedene Grundfuttermittel.

  11. E-Commerce. Auswirkungen auf den Bucheinzelhandel. Mit Ergebnissen der zweiten Branchenumfrage in der Region Franken

    OpenAIRE

    Kuhn, Axel

    2008-01-01

    2004 erschienen mit E-Commerce. Auswirkungen auf den Bucheinzelhandel die Ergebnisse einer empirischen Studie des Forschungsprojekts Electronic Publishing und E-Commerce im Buchhandel, welche die Auswirkungen des elektronischen Handels auf die Strukturen des Buchhandels untersuchten. Die Studie wurde 2007 wiederholt, um aus den Veränderungen Erkenntnisse über die Etablierung des elektronischen Handels im Bucheinzelhandel zu gewinnen. Die hier vorliegenden Ergebnisse zeigen auf, wie sich die E...

  12. Photovoltaik – Soziale und ökonomische Faktoren des Investitionsverhaltens auf landwirtschaftlichen Betrieben

    OpenAIRE

    Plaas, Elke; Bergmann, Holger

    2013-01-01

    In diesem Beitrag wird der Frage nachgegangen, welchen Einfluss Familie und soziales Umfeld auf Investitionen in erneuerbare Energieerzeugung auf landwirtschaftlichen Betrieben in den Jahren bis 2012 gehabt haben. In einer mündlichen Befragung im Rahmen der EUROTIER 2012 wurden 235 Landwirt/innen befragt. Die Analyse der erhobenen Daten wurde auf die Grundlage des Lebenszyklusmodells gestellt, um zu überprüfen, ob die Mehrzahl der Landwirte landwirtschaftliche Einkommen maximieren oder satisf...

  13. Auswirkung von Umweltchemikalien auf die Biologie von Chironomiden und Fischen als deren Prädatoren

    OpenAIRE

    Langer-Jaesrich, Miriam

    2012-01-01

    Im Rahmen der Dissertation wurden in mehreren Teilprojekten die Auswirkungen von Umweltchemikalien auf Chironomiden als Schlüsselorganismen in aquatisch-benthischen Lebensräumen untersucht. Dabei lag der Fokus besonders auf der Erfassung von nicht-standardisierten Endpunkten und Bioindikatoren sowie auf der Bearbeitung einer weiterführenden ökologisch relevanten Fragestellung zum Räuber-Beute-Verhältnis unter Schadstoffeinfluss. Im ersten Teil der Dissertation wurde das herkömmliche Standa...

  14. The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

    Science.gov (United States)

    Tichauer, Kenneth M.

    2016-03-01

    One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

  15. Real-time targeted molecular imaging using singular value spectra properties to isolate the adherent microbubble signal

    International Nuclear Information System (INIS)

    Ultrasound-based real-time molecular imaging in large blood vessels holds promise for early detection and diagnosis of various important and significant diseases, such as stroke, atherosclerosis, and cancer. Central to the success of this imaging technique is the isolation of ligand–receptor bound adherent microbubbles from free microbubbles and tissue structures. In this paper, we present a new approach, termed singular spectrum-based targeted molecular (SiSTM) imaging, which separates signal components using singular value spectra content over local regions of complex echo data. Simulations were performed to illustrate the effects of acoustic target motion and harmonic energy on SiSTM imaging-derived measurements of statistical dimensionality. In vitro flow phantom experiments were performed under physiologically realistic conditions (2.7 cm s−1 flow velocity and 4 mm diameter) with targeted and non-targeted phantom channels. Both simulation and experimental results demonstrated that the relative motion and harmonic characteristics of adherent microbubbles (i.e. low motion and large harmonics) yields echo data with a dimensionality that is distinct from free microbubbles (i.e. large motion and large harmonics) and tissue (i.e. low motion and low harmonics). Experimental SiSTM images produced the expected trend of a greater adherent microbubble signal in targeted versus non-targeted microbubble experiments (P < 0.05, n = 4). The location of adherent microbubbles was qualitatively confirmed via optical imaging of the fluorescent DiI signal along the phantom channel walls after SiSTM imaging. In comparison with two frequency-based real-time molecular imaging strategies, SiSTM imaging provided significantly higher image contrast (P < 0.001, n = 4) and a larger area under the receiver operating characteristic curve (P < 0.05, n = 4). (paper)

  16. Molecular Imaging on the Cerebral Pathological Damage Target of Ketamine Dependence

    Directory of Open Access Journals (Sweden)

    YANG Hong-jie1,2;HU Shu1;JIA Shao-wei1;GAO Zhou1;WANG Tong3;ZHAO Zheng-qin1

    2014-02-01

    Full Text Available To study the cerebral pathological damage target which result from abusing ketamine through molecular imaging techniques, 20 cases of ketamine dependent patients looking for treatment at the Peking University Shenzhen Hospital and 31 healthy volunteers were included in this study, all of them got brain SPECT DAT imaging. The results were analyzed by SPSS 16.0. The bilateral caudate nucleus and putamen of healthy volunteers were roughly equally large, and the radioactive distribution of DAT in healthy volunteers were uniform and symmetrical. The bilateral corpora striatum showed typical “panda eyes” pattern. But the bilateral corpora striatum of ketamine dependent patients got smaller in shape, got disorders in pattern, and the radioactive distribution of DAT reduced or defected or even got disturbance and with much more non-specific radioactive. The V, m and Ra of bilateral corpora striatum in ketamine dependent patients were (21.03±3.15) cm3, (22.08±3.31) g and (5.37±1.08) %, respectively, which were significantly lower than the healthy volunteers (p<0.01. The cerebral pathological damage target which resulted from abusing ketamine was similar to those of compound codeine phosphate antitussive solution dependence, heroin dependence and MDMA dependence, all of these psychoactive substances damaged the function of DAT.

  17. Dynamical image-charge effect in molecular tunnel junctions: Beyond energy level alignment

    Science.gov (United States)

    Jin, Chengjun; Thygesen, Kristian S.

    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 Z2, where Z is the quasiparticle renormalization factor, compared to the static IC approximation. We show that Z can be expressed either in terms of the plasma frequency of the electrode or as the overlap between electrode wave functions corresponding to an empty and filled level, respectively. First-principles GW calculations for benzene-diamine connected to gold electrodes show 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.

  18. Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry.

    Science.gov (United States)

    Fülöp, Annabelle; Sammour, Denis A; Erich, Katrin; von Gerichten, Johanna; van Hoogevest, Peter; Sandhoff, Roger; Hopf, Carsten

    2016-01-01

    Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs. PMID:27650487

  19. Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

    Directory of Open Access Journals (Sweden)

    Zhenfeng Zheng

    Full Text Available BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI and magnetic resonance (MR imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI sequences accompanied by an array spatial sensitivity encoding technique (ASSET. Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD, fractional anisotropy (FA and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3 were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002 and λ1 (r = 0.277, P = 0.018 positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033 negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.

  20. Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals.

    Science.gov (United States)

    Goeman, Frauke; Manni, Isabella; Artuso, Simona; Ramachandran, Balaji; Toietta, Gabriele; Bossi, Gianluca; Rando, Gianpaolo; Cencioni, Chiara; Germoni, Sabrina; Straino, Stefania; Capogrossi, Maurizio C; Bacchetti, Silvia; Maggi, Adriana; Sacchi, Ada; Ciana, Paolo; Piaggio, Giulia

    2012-04-01

    In vivo imaging involving the use of genetically engineered animals is an innovative powerful tool for the noninvasive assessment of the molecular and cellular events that are often targets of therapy. On the basis of the knowledge that the activity of the nuclear factor-Y (NF-Y) transcription factor is restricted in vitro to proliferating cells, we have generated a transgenic reporter mouse, called MITO-Luc (for mitosis-luciferase), in which an NF-Y-dependent promoter controls luciferase expression. In these mice, bioluminescence imaging of NF-Y activity visualizes areas of physiological cell proliferation and regeneration during response to injury. Using this tool, we highlight for the first time a role of NF-Y activity on hepatocyte proliferation during liver regeneration. MITO-Luc reporter mice should facilitate investigations into the involvement of genes in cell proliferation and provide a useful model for studying aberrant proliferation in disease pathogenesis. They should be also useful in the development of new anti/proproliferative drugs and assessment of their efficacy and side effects on nontarget tissues. PMID:22379106

  1. Magnetic Resonance Spectroscopy: An In Vivo Molecular Imaging Biomarker for Parkinson’s Disease?

    Directory of Open Access Journals (Sweden)

    Rosella Ciurleo

    2014-01-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder caused by selective loss of dopaminergic neurons in the substantia nigra pars compacta which leads to dysfunction of cerebral pathways critical for the control of movements. The diagnosis of PD is based on motor symptoms, such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor, which are evident only after the degeneration of a significant number of dopaminergic neurons. Currently, a marker for early diagnosis of PD is still not available. Consequently, also the development of disease-modifying therapies is a challenge. Magnetic resonance spectroscopy is a quantitative imaging technique that allows in vivo measurement of certain neurometabolites and may produce biomarkers that reflect metabolic dysfunctions and irreversible neuronal damage. This review summarizes the abnormalities of cerebral metabolites found in MRS studies performed in patients with PD and other forms of parkinsonism. In addition, we discuss the potential role of MRS as in vivo molecular imaging biomarker for early diagnosis of PD and for monitoring the efficacy of therapeutic interventions.

  2. Molecular markers and imaging tools to identify malignant potential in Barrett’s esophagus

    Institute of Scientific and Technical Information of China (English)

    Michael; Bennett; Hiroshi; Mashimo

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and sur-veillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of highrisk lesions in Barrett’s esophagus.

  3. Development of a novel molecular sensor for imaging estrogen receptor-coactivator protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Madryn C Lake

    Full Text Available Anti-estrogens, in particular tissue selective anti-estrogens, have been the bedrock of adjuvant therapy for patients with estrogen receptor alpha (ERα positive breast cancer. Though current therapies have greatly enhanced patient prognosis, there continues to be an impetus for the development of improved anti-estrogens. ERα is a nuclear receptor transcription factor which activates gene expression through the recruitment of transcriptional coactivator proteins. The SRC family of coactivators, which includes AIB1, has been shown to be of particular importance for ERα mediated transcription. ERα-AIB1 interactions are indicative of gene expression and are inhibited by anti-estrogen treatment. We have exploited the interaction between ERα and AIB1 as a novel method for imaging ERα activity using a split luciferase molecular sensor. By producing a range of ERα ligand binding domain (ER-LBD and AIB1 nuclear receptor interacting domain (AIB-RID N- and C-terminal firefly luciferase fragment fusion proteins, constructs which exhibited more than a 10-fold increase in luciferase activity with E2 stimulation were identified. The specificity of the E2-stimulated luciferase activity to ERα-AIB1 interaction was validated through Y537S and L539/540A ER-LBD fusion protein mutants. The primed nature of the split luciferase assay allowed changes in ERα activity, with respect to the protein-protein interactions preceding transcription, to be assessed soon after drug treatment. The novel assay split luciferase detailed in this report enabled modulation of ERα activity to be sensitively imaged in vitro and in living subjects and potentially holds much promise for imaging the efficacy of novel ERα specific therapies.

  4. 分子影像学教学体系构建探讨%On Molecular Imaging Teaching System Construction

    Institute of Scientific and Technical Information of China (English)

    陈多芳

    2014-01-01

    分子影像学是一门新兴的交叉学科,已经成为现代生命科学研究最重要的技术手段之一,代表了未来医学影像发展的方向。本文针对分子影像学特点,结合我校生命科学技术学院在分子影像学领域的研究成果以及与医院的合作基础,在教学内容、教学模式以及考评方式等方面展开研究,将生命科学与信息学科和临床医学交叉,建立分子影像学教学体系,为培养理工医复合型分子影像学人才奠定基础。%Molecular imaging is an emerging interdisciplinary, has become one of the most important techniques of modern life sciences, medical imaging represents the direction of future development. In this paper, molecular imaging features, com-bined with research in Life Science and Technology in the field of molecular imaging as well as the basis for cooperation with our university hospital, a study in teaching content, teaching models and evaluation methods, the life science and information science and clinical cross, build molecular imaging teaching system, laying the foundation for training medical complex poly-technic molecular imaging professionals.

  5. mRNA decay factor AUF1 binds the internal ribosomal entry site of enterovirus 71 and inhibits virus replication.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lin

    Full Text Available AU-rich element binding factor 1 (AUF1 has a role in the replication cycles of different viruses. Here we demonstrate that AUF1 binds the internal ribosome entry site (IRES of enterovirus 71 (EV71 and negatively regulates IRES-dependent translation. During EV71 infection, AUF1 accumulates in the cytoplasm where viral replication occurs, whereas AUF1 localizes predominantly in the nucleus in mock-infected cells. AUF1 knockdown in infected cells increases IRES activity and synthesis of viral proteins. Taken together, the results suggest that AUF1 interacts with the EV71 IRES to negatively regulate viral translation and replication.

  6. The role of MRI in suspected inner ear malformations; Stellenwert der MRT bei Verdacht auf Innenohrmissbildung

    Energy Technology Data Exchange (ETDEWEB)

    Koesling, S.; Juettemann, S.; Amaya, B. [Halle-Wittenberg Univ., Halle (Germany). Klinik fuer Diagnostische Radiologie; Rasinski, C.; Bloching, M. [Halle-Wittenberg Univ., Halle (Germany). Klinik fuer Hals-, Nasen-, Ohrenkrankheiten; Koenig, E. [Leipzig Univ. (Germany). Klinik fuer Hals-, Nasen-, Ohrenkrankheiten

    2003-12-01

    Purpose: This is a prospective analysis of the value of MRI in suspected inner ear malformations. Materials and Methods: In 50 patients (43 children and young adults, 7 adults) with suspected inner ear malformation MRI (1.5 T) was performed. In addition, 42 of these patients underwent CT. For the analysis of the inner ear structures, the constructive interference in steady state (CISS) sequence with 0.7 mm slice thickness was used. Functional tests revealed a sensorineural hearing loss or deafness in 82 temporal bones (TB) and a combined hearing loss in 4 TB. The hearing loss was unilateral in 14 patients. MRI and CT findings were compared. Results: Imaging findings were normal in 58 TB. The pathological findings included inner ear malformations (35 TB), inflammatory changes (4 TB), partial obliteration of labyrinth (2 TB) and congenital aural atresia (1 TB). An isolated absence of the cochlear nerve (1 TB) could only be found by MRI. In the remaining cases, an inner ear malformation was diagnosed by MRI and CT with the same confidence but MRI was superior in displaying the fine details. Conclusions: MRI will become the method of choice in the diagnosis of inner ear malformations. (orig.) [German] Ziel: Das Ziel der Arbeit bestand in einer prospektiven Analyse des Stellenwertes der MRT bei Verdacht auf eine Innenohrmissbildung. Material und Methodik: 50 Patienten (43 Kinder und Jugendliche, 7 Erwachsene) mit dringendem Verdacht auf eine Innenohrmissbildung erhielten eine MRT-Untersuchung (1,5 T), bei 42 dieser Patienten wurde auch eine CT durchgefuehrt. Bei der Beurteilung der Innenohrstrukturen kam die CISS-Sequenz mit einer Schichtdicke von 0,7 mm zur Anwendung. Durch Funktionstests wurde an 82 Schlaefenbeinen (SB) eine Innenohrhoerstoerung und an 4 SB eine kombinierte Hoerstoerung diagnostiziert. 14 Patienten hatten eine einseitige Hoerstoerung. MRT- und CT-Ergebnisse wurden verglichen. Ergebnisse: Einen bildgebenden Normalbefund wiesen 58 SB auf. Folgende

  7. Evaluation of the effectiveness of the German Federal Government with respect to sustainable mobility: Analyse rechtlicher, fiskalpolitischer und softer Maßnahmen auf Bundesebene

    OpenAIRE

    Gruber, Robert

    2012-01-01

    Transport, insbesondere der Straßenpersonenverkehr, verursacht massive Umweltauswirkungen und Treibhausgasemissionen, die bisher nur unzureichend politisch bekämpft wurden. Gerade Deutschland mit seiner starken Automobilindustrie und dem gut ausgebauten Straßennetz ist hier keine Ausnahme. Diese Arbeit analysiert die regulatorischen, fiskalischen und weichen Maßnahmen (wie Image-Kampagnen) für nachhaltigen Personenlandverkehr der Deutschen Bundesregierung. Sie zeigt die Fixierung auf teure te...

  8. Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-08-01

    The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis. PMID:26079611

  9. Auswirkungen der EU-Erweiterung auf die deutsche Bauwirtschaft

    OpenAIRE

    Reuter, Richard

    2011-01-01

    Ab dem 1. Mai 2011 können Arbeitnehmer aus den 2004 der EU beigetretenen Staaten ohne Beschränkungen einen Arbeitsplatz in Deutschland annehmen. Die Bauwirtschaft hatte zum Zeitpunkt der EU-Osterweiterung besonders große Befürchtungen, dass es zu ruinöser Konkurrenz auf den Baumärkten kommen könnte. Allerdings hatte nach Auffassung des Autors die Einführung eines Bau-Mindestlohns mit dem Arbeitnehmerentsendegesetz 1997 für die Bauwirtschaft wesentlich gravierendere Folgen als die Osterweiteru...

  10. Die Auswirkungen von Pinostrobin auf Endothelzellen der humanen Nabelschnurvene

    OpenAIRE

    Siekmann, Tabea Ricarda Luise

    2014-01-01

    Pinostrobin wirkt antiproliferativ auf HUVEC. Je höher die Konzentration dieses Flavonoids ist, desto antiproliferativer wirkt es. Seine Wirkung entfaltet Pinostrobin im Laufe von 48 Stunden. Möglich wäre eine zytotoxische Reaktion durch Membraninstabilität bei einer gravierenden Leifähigkeitsänderung durch hohe Pinostrobindosen. Pinostrobin bewirkt eine Calciumerhöhung im Intrazellulärraum. Das Calcium strömt entweder aus dem Extrazellulärraum in die Zelle ein, oder es wird aus intrazellu...

  11. Investigating the dopaminergic synapse in vivo. II. Molecular imaging studies in small laboratory animals.

    Science.gov (United States)

    Nikolaus, Susanne; Larisch, Rolf; Beu, Markus; Antke, Christina; Kley, Konstantin; Forutan, Farhad; Wirrwar, Andreas; Müller, Hans-Wilhelm

    2007-01-01

    Dopaminergic synaptic function may be assessed either at the presynaptic terminal or at the postsynaptic binding sites using molecular in vivo imaging methods. Apart from the density of binding sites, parameters such as alterations in dopamine synthesis, dopamine storage or dopamine release can be quantified either by application of specific radiotracers or by assessing the competition between the exogenous radioligand and endogenous dopamine. The performance of animal studies allows the induction of specific short-term or long-term synaptic conditions via pharmacological challenges or infliction of neurotoxic lesions. Therefore, small laboratory animals such as rats and mice have become invaluable models for a variety of human disorders. This article gives an overview of those small animal studies which have been performed so far on dopaminergic neurotransmission using in vivo imaging methods, with a special focus on the relevance of findings within the functional entity of the dopaminergic synapse. Taken together, in vivo investigations on animal models of Parkinson's disease showed decreases of dopamine storage, dopamine release and dopamine transporter binding, no alterations of dopamine synthesis and DA release, and either increases or no alterations of D2 receptor binding, while in vivo investigations of animal models of Huntington's disease. showed decreases of DAT and D1 receptor binding. For D2 receptor binding, both decreases and increases have been reported, dependent on the radioligand employed. Substances of abuse, such as alcohol, amphetamine and methylphenidate, led to an increase of dopamine release in striatal regions. This held for the acute application of substances to both healthy animals and animal models of drug abuse. Findings also showed that chronic application of cocaine induced long-term reductions of both D1 and D2 receptor binding, which disappeared after several weeks of withdrawal. Finally, preliminary results yielded the first

  12. Molecular image in biomedical research. Molecular imaging unit of the National Cancer Research Center; Imagen molecular an investigation biomedica. La Unidad de Imagen Molecular del Centro Nacional de Investigaciones Oncologicas

    Energy Technology Data Exchange (ETDEWEB)

    Perez Bruzon, J.; Mulero Anhiorte, F.

    2010-07-01

    This article has two basic objectives. firstly, it will review briefly the most important imaging techniques used in biomedical research indicting the most significant aspects related to their application in the preclinical stage. Secondly, it will present a practical application of these techniques in a pure biomedical research centre (not associated to a clinical facility). Practical aspects such as organisation, equipment, work norms, shielding of the Spanish National Cancer Research Centre (CNIO) Imaging Unit will be shown. This is a pioneering facility in the application of these techniques in research centres without any dependence or any direct relationship with other hospital Nuclear Medicine services. (Author) 7 refs.

  13. Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications

    International Nuclear Information System (INIS)

    Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within tissue for molecular imaging and phototherapy applications. While several studies have investigated the total Cherenkov light yield from radionuclides in units of [photons/decay], further consideration of the light propagation in tissue is necessary to fully consider the utility of this signal in vivo. Therefore, to help further guide the development of this novel field, quantitative estimates of the light fluence rate of Cherenkov radiation from both radionuclides and radiotherapy beams in a biological tissue are presented for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.01–1 nW cm−2 per MBq g−1 for radionuclides, and 1–100 μW cm−2 per Gy s−1 for external radiotherapy beams, dependent on the given waveband, optical properties, and radiation source. For phototherapy applications, the total light fluence was found to be on the order of nJ cm−2 for radionuclides, and mJ cm−2 for radiotherapy beams. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at such exceedingly low fluence values. The results of this study are publicly available for distribution online at www.dartmouth.edu/optmed/. (paper)

  14. Diagnostic Workup and Costs of a Single Supplemental Molecular Breast Imaging Screen of Mammographically Dense Breasts

    Science.gov (United States)

    Hruska, Carrie B.; Conners, Amy Lynn; Jones, Katie N.; O’Connor, Michael K.; Moriarty, James P.; Boughey, Judy C.; Rhodes, Deborah J.

    2016-01-01

    OBJECTIVE The purpose of this study was to examine additional diagnostic workup and costs generated by addition of a single molecular breast imaging (MBI) examination to screening mammography for women with dense breasts. SUBJECTS AND METHODS Women with mammographically dense breasts presenting for screening mammography underwent adjunct MBI performed with 300 MBq 99mTc-sestamibi and a direct-conversion cadmium-zinc-telluride dual-head gamma camera. All subsequent imaging tests and biopsies were tracked for a minimum of 1 year. The positive predictive value of biopsies performed (PPV3), benign biopsy rate, cost per patient screened, and cost per cancer detected were determined. RESULTS A total of 1651 women enrolled in the study. Among the 1585 participants with complete reference standard, screening mammography alone prompted diagnostic workup of 175 (11.0%) patients and biopsy of 20 (1.3%) and yielded five malignancies (PPV3, 25%). Results of combined screening mammography plus MBI prompted diagnostic workup of 279 patients (17.6%) and biopsy of 67 (4.2%) and yielded 19 malignancies (PPV3, 28.4%). The benign biopsy rates were 0.9% (15 of 1585) for screening mammography alone and 3.0% (48 of 1585) for the combination (p cost per patient screened from $176 for mammography alone to $571 for the combination. However, cost per cancer detected was lower for the combination ($47,597) than for mammography alone ($55,851). CONCLUSION The addition of MBI to screening mammography of women with dense breasts increased the overall costs and benign biopsy rate but also increased the cancer detection rate, which resulted in a lower cost per cancer detected than with screening mammography alone. PMID:26001247

  15. Molecular analysis of arterial remodeling: a novel application of infrared imaging

    Science.gov (United States)

    Herman, Brad C.; Kundi, Rishi; Yamanouchi, Dai; Kent, K. Craig; Liu, Bo; Pleshko, Nancy

    2009-02-01

    Arterial remodeling, i.e. changes in size and/or structure of arteries, plays an important role in vascular disease. Conflicting findings have been reported as to whether an abundance of collagen causes inward or outward remodeling, phenomena that result in either a smaller or larger lumen, respectively. We hypothesize that the amount, type and quality of collagen influence the remodeling response. Here, we create mechanical injury to the rat carotid artery using a balloon catheter, and this leads to inward remodeling. Treatment of the artery with Connective Tissue Growth Factor (CTGF) causes outward remodeling. We investigated the arterial composition in injured CTGF-treated and non-CTGF-treated and sham CTGF-treated and non-CTGF treated arteries 14 days post-injury (n = 7-8 per group) using infrared imaging. A Perkin Elmer Spotlight Spectrum 300 FT-IR microscope was used for data collection. Cross-sections of paraffinembedded arteries were scanned at 2 cm-1 spectral resolution with spatial resolution of 6.25 μm/pixel, and data analyzed using Malvern Instruments ISys 5.0. Post-injury, we found a nearly 50% reduction in the average 1338/AM2 area ratio (correlated to collagen helical integrity). The most dramatic change was a 600% increase in the 1660/1690 peak height ratio, which has previously been related to collagen crosslink maturity. In all cases, CTGF treatment resulted in the observed changes in peak parameters normalized back to control values. Overall, these preliminary studies demonstrate that infrared imaging can provide insight into the underlying molecular changes that contribute to arterial disease.

  16. Beratung auf Facebook und Twitter? Wie virtuelle Beratungsangebote auf die neuen Leitmedien reagieren können

    Directory of Open Access Journals (Sweden)

    Heinz Thiery

    2011-10-01

    Full Text Available Facebook und Twitter erleben aktuell einen enormen Zulauf. Beide konkurrieren um die Vorherrschaft als Leitmedium des WEB 2.0. Mit ihrem Angebotsmix sind sie nicht nur für die Mehrheit der Internetnutzer attraktiv, sie prägen darüber hinaus die Nutzungsgewohnheiten, die sich in Form einer spezifischen „Internetkultur“ etablieren. Zudem forcieren die Leitmedien technische Trends wie beispielsweise das „mobile computing“. Der Artikel beschäftigt sich mit der Frage, welche Auswirkungen diese Entwicklungen auf die professionellen Onlineberatungsangebote hat und wie ihnen begegnet werden kann.

  17. Nanoscale Chemical Imaging of a Dynamic Molecular Phase Boundary with Ultrahigh Vacuum Tip-Enhanced Raman Spectroscopy.

    Science.gov (United States)

    Jiang, Nan; Chiang, Naihao; Madison, Lindsey R; Pozzi, Eric A; Wasielewski, Michael R; Seideman, Tamar; Ratner, Mark A; Hersam, Mark C; Schatz, George C; Van Duyne, Richard P

    2016-06-01

    Nanoscale chemical imaging of a dynamic molecular phase boundary has broad implications for a range of problems in catalysis, surface science, and molecular electronics. While scanning probe microscopy (SPM) is commonly used to study molecular phase boundaries, its information content can be severely compromised by surface diffusion, irregular packing, or three-dimensional adsorbate geometry. Here, we demonstrate the simultaneous chemical and structural analysis of N-N'-bis(2,6-diisopropylphenyl)-1,7-(4'-t-butylphenoxy)perylene-3,4:9,10-bis(dicarboximide) (PPDI) molecules by UHV tip-enhanced Raman spectroscopy. Both condensed and diffusing domains of PPDI coexist on Ag(100) at room temperature. Through comparison with time-dependent density functional theory simulations, we unravel the orientation of PPDI molecules at the dynamic molecular domain boundary with unprecedented ∼4 nm spatial resolution. PMID:27183322

  18. Isovlavone und Soja haben keine Wirkung auf die Knochendichte

    Directory of Open Access Journals (Sweden)

    Burckhardt P

    2013-01-01

    Full Text Available Isoflavone sind eine Untergruppe von östrogenähnlichen Pflanzensteroiden, welche sich vor allem in Sojaprodukten finden. Es wird ihnen eine östrogenähnliche, knochenschützende Wirkung zugeschrieben. Aber die genaue Analyse der wissenschaftlichen Literatur ergibt, dass abgesehen von den Tierversuchen nur wenige klinische Versuche mit diesen Substanzen als kontrollierte, randomisierte Studien durchgeführt worden sind. Dabei wurden positive Teilresultate hochgespielt. Wissenschaftliche Metaanalysen dieser Versuche kamen eindeutig zum Schluss, dass Soja und Isoflavone keine Wirkung auf die Knochendichte aufzeigen. Es hat sich aber ergeben, dass Equol, das von bestimmten Bakterien im Darm aus dem Isoflavon Daidzein gebildet wird, die Substanz ist, welche am meisten mit den Östrogen-Rezeptoren beta bindet, und dass nur ca. 30 % der Frauen zur Equol-Bildung befähigt sind, in Asien aber 50 %. Deswegen wurden auch mit Equol klinische Versuche durchgeführt, und zwar bei Frauen, die kein Equol bilden konnten. Aber wiederum blieben die Resultate negativ bezüglich einer Wirkung auf die Knochendichte. Es muss daher geschlossen werden, dass Isoflavone und Equol in der Prävention und Therapie der Osteoporose wirkungslos sind.

  19. Einfluss von Konstruktion und Betriebsweise von Trinkwasserinstallationen auf das Wachstum von Mikroorganismen im Trinkwasser

    OpenAIRE

    Astitouh, F. (Fariha)

    2013-01-01

    Das Wachstumsverhalten von Biofilmen und Krankheitserregern im Wasser aus Trinkwasserinstallationen wird durch Temperatur und Stagnation beeinflusst. Die Vermeidung von „lauwarmen“ Temperaturen, die das Legionellenwachstum begünstigt, stellt höhere Anforderungen an Konstruktion und Betriebsweise von Kaltwassersystemen. Diese Arbeit analysiert Konstruktionsprinzipien von Stockwerksinstallationen auf den Einfluss auf das Wachstum von Mikroorganismen im Trinkwasser „Kalt“. Die Versuchsanlage sim...

  20. Metal clusters on supported argon layers; Metallcluster auf dielektrischen Substraten

    Energy Technology Data Exchange (ETDEWEB)

    Faber, Bernhard

    2011-10-21

    The deposition of small sodium clusters on supported Ar(001)-surfaces is simulated. Theoretical description is achieved by a hierarchical model consisting of time-dependent DFT and molecular dynamics. The valence electrons of the sodium atoms are considered by Kohn-Sham-Scheme with self interaction correction. The interaction of argon atoms and sodium ions is described by atom-atom potentials whereas the coupling to the QM electrons is done by local pseudo-potentials. A decisive part of the model is the dynamical polarizability of the rare-gas atoms. The optional metal support is considered by the method of image charges. The influence of the forces caused by image charges and the influence of the number of argon monolayers on structure, optical response and deposition dynamics of Na{sub 6} and Na{sub 8} is investigated. There is very little influence on cluster structure and only a small shift of the cluster perpendicular to the surface. Concerning optical response the position of the Mie plasmon peak stays robust whereas the details of spectral fragmentation react very sensitively to changes. The forces caused by image charges of the metal support play only a little role with the dynamics of deposition while the thickness of the argon surface strongly influences the dissipation. (orig.)

  1. Monitoring the Spatiotemporal Activities of miRNAs in Small Animal Models Using Molecular Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Patrick Baril

    2015-03-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy.

  2. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  3. Image reconstruction of fluorescent molecular tomography based on the tree structured Schur complement decomposition

    Directory of Open Access Journals (Sweden)

    Wang Jiajun

    2010-05-01

    Full Text Available Abstract Background The inverse problem of fluorescent molecular tomography (FMT often involves complex large-scale matrix operations, which may lead to unacceptable computational errors and complexity. In this research, a tree structured Schur complement decomposition strategy is proposed to accelerate the reconstruction process and reduce the computational complexity. Additionally, an adaptive regularization scheme is developed to improve the ill-posedness of the inverse problem. Methods The global system is decomposed level by level with the Schur complement system along two paths in the tree structure. The resultant subsystems are solved in combination with the biconjugate gradient method. The mesh for the inverse problem is generated incorporating the prior information. During the reconstruction, the regularization parameters are adaptive not only to the spatial variations but also to the variations of the objective function to tackle the ill-posed nature of the inverse problem. Results Simulation results demonstrate that the strategy of the tree structured Schur complement decomposition obviously outperforms the previous methods, such as the conventional Conjugate-Gradient (CG and the Schur CG methods, in both reconstruction accuracy and speed. As compared with the Tikhonov regularization method, the adaptive regularization scheme can significantly improve ill-posedness of the inverse problem. Conclusions The methods proposed in this paper can significantly improve the reconstructed image quality of FMT and accelerate the reconstruction process.

  4. Momentum imaging spectrometer for molecular fragmentation dynamics induced by pulsed electron beam

    International Nuclear Information System (INIS)

    A momentum imaging spectrometer has been built for studying the electron impact molecular fragmentation dynamics. The setup consists of a pulsed electron gun and a time of flight system as well as a two-dimensional time and position sensitive multi-hit detector. The charged fragments with kinetic energy up to 10 eV can be detected in 4π solid angles and their three-dimensional momentum vectors can be reconstructed. The apparatus is tested by electron impact ionization of Ar and dissociative ionization of CO2. By analyzing the ion-ion coincidence spectra, the complete and incomplete Coulomb fragmentation channels for CO22+ and CO23+ are identified. The kinetic energy release (KER) and angular correlation for the two-body breakup channel CO22+*→ O++ CO+ are reported. The peak value of total KER is found to be 6.8 eV which is consistent with the previous photoion-photoion coincidence studies, and the correlation angle of O+ and CO+ is also explicitly determined to be 172.5°

  5. Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging.

    Science.gov (United States)

    Belliere, Julie; Martinez de Lizarrondo, Sara; Choudhury, Robin P; Quenault, Aurélien; Le Béhot, Audrey; Delage, Christine; Chauveau, Dominique; Schanstra, Joost P; Bascands, Jean-Loup; Vivien, Denis; Gauberti, Maxime

    2015-01-01

    Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI. PMID:26379785

  6. Mapping molecular adhesion sites inside SMIL coated capillaries using atomic force microscopy recognition imaging.

    Science.gov (United States)

    Leitner, Michael; Stock, Lorenz G; Traxler, Lukas; Leclercq, Laurent; Bonazza, Klaus; Friedbacher, Gernot; Cottet, Hervé; Stutz, Hanno; Ebner, Andreas

    2016-08-01

    Capillary zone electrophoresis (CZE) is a powerful analytical technique for fast and efficient separation of different analytes ranging from small inorganic ions to large proteins. However electrophoretic resolution significantly depends on the coating of the inner capillary surface. High technical efforts like Successive Multiple Ionic Polymer Layer (SMIL) generation have been taken to develop stable coatings with switchable surface charges fulfilling the requirements needed for optimal separation. Although the performance can be easily proven in normalized test runs, characterization of the coating itself remains challenging. Atomic force microscopy (AFM) allows for topographical investigation of biological and analytical relevant surfaces with nanometer resolution and yields information about the surface roughness and homogeneity. Upgrading the scanning tip to a molecular biosensor by adhesive molecules (like partly inverted charged molecules) allows for performing topography and recognition imaging (TREC). As a result, simultaneously acquired sample topography and adhesion maps can be recorded. We optimized this technique for electrophoresis capillaries and investigated the charge distribution of differently composed and treated SMIL coatings. By using the positively charged protein avidin as a single molecule sensor, we compared these SMIL coatings with respect to negative charges, resulting in adhesion maps with nanometer resolution. The capability of TREC as a functional investigation technique at the nanoscale was successfully demonstrated. PMID:27265903

  7. Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using (13)C Metabolic Contrast Agents.

    Science.gov (United States)

    Coffey, Aaron M; Shchepin, Roman V; Truong, Milton L; Wilkens, Ken; Pham, Wellington; Chekmenev, Eduard Y

    2016-08-16

    An open-source hyperpolarizer producing (13)C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2-3 mL) of hyperpolarized (13)C-succinate with %P13C ∼ 28% and 30 mM concentration and (13)C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized (13)C-phospholactate to (13)C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice (13)C MRI after tail vein injection of hyperpolarized (13)C-phospholactate in mice. PMID:27478927

  8. Herschel-SPIRE Imaging Spectroscopy of Molecular Gas in M82

    CERN Document Server

    Kamenetzky, J; Rangwala, N; Maloney, P; Bradford, M; Wilson, C D; Bendo, G J; Baes, M; Boselli, A; Cooray, A; Isaak, K G; Lebouteiller, V; Madden, S; Panuzzo, P; Schirm, M R P; Spinoglio, L; Wu, R

    2012-01-01

    We present new Herschel-SPIRE imaging spectroscopy (194-671 microns) of the bright starburst galaxy M82. Covering the CO ladder from J=4-3 to J=13-12, spectra were obtained at multiple positions for a fully sampled ~ 3 x 3 arcminute map, including a longer exposure at the central position. We present measurements of 12CO, 13CO, [CI], [NII], HCN, and HCO+ in emission, along with OH+, H2O+ and HF in absorption and H2O in both emission and absorption, with discussion. We use a radiative transfer code and Bayesian likelihood analysis to model the temperature, density, column density, and filling factor of multiple components of molecular gas traced by 12CO and 13CO, adding further evidence to the high-J lines tracing a much warmer (~ 500 K), less massive component than the low-J lines. The addition of 13CO (and [CI]) is new and indicates that [CI] may be tracing different gas than 12CO. No temperature/density gradients can be inferred from the map, indicating that the single-pointing spectrum is descriptive of th...

  9. Signatures of infall motions in the images of the molecular emission of G31 HMC

    CERN Document Server

    Mayen-Gijon, J M; Osorio, M; Rodriguez, L F; Lizano, S; Gomez, J F; Carrasco-Gonzalez, C

    2013-01-01

    Although gravitational collapse is supposed to play an essential role in the star formation process, infall motions have been always elusive to detect. So far, only a few observational signatures have been commonly used to claim for the presence of infall. Often these features consist in either "blue-asymmetries" or absorption at red-shifted velocities (e.g., inverse P-Cygni profiles). Both signatures are based only on the shape of the line profile and they do not guarantee by themselves the presence of dominant infall motions. More robust "mapping signatures" can be obtained from images that angularly resolve the infalling gas. Here we present VLA observations of the ammonia inversion transitions (2,2), (3,3), (4,4), (5,5), and (6,6) towards the hot molecular core (HMC) near G31.41+0.31 that show the signatures of protostellar infall theoretically predicted by Anglada et al. (1991). The intensity of the ammonia emission is compact and sharply increases towards the centre in the blue-shifted velocity channel ...

  10. Application of imaging mass spectrometry for the molecular diagnosis of human breast tumors.

    Science.gov (United States)

    Mao, Xinxin; He, Jiuming; Li, Tiegang; Lu, Zhaohui; Sun, Jian; Meng, Yunxiao; Abliz, Zeper; Chen, Jie

    2016-01-01

    Distinguishing breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS) is a key step in breast surgery, especially to determine whether DCIS is associated with tumor cell micro-invasion. However, there is currently no reliable method to obtain molecular information for breast tumor analysis during surgery. Here, we present a novel air flow-assisted ionization (AFAI) mass spectrometry imaging method that can be used in ambient environments to differentiate breast cancer by analyzing lipids. In this study, we demonstrate that various subtypes and histological grades of IDC and DCIS can be discriminated using AFAI-MSI: phospholipids were more abundant in IDC than in DCIS, whereas fatty acids were more abundant in DCIS than in IDC. The classification of specimens in the subtype and grade validation sets showed 100% and 78.6% agreement with the histopathological diagnosis, respectively. Our work shows the rapid classification of breast cancer utilizing AFAI-MSI. This work suggests that this method could be developed to provide surgeons with nearly real-time information to guide surgical resections. PMID:26868906

  11. In vivo targeted molecular magnetic resonance imaging of free radicals in diabetic cardiomyopathy within mice.

    Science.gov (United States)

    Towner, R A; Smith, N; Saunders, D; Carrizales, J; Lupu, F; Silasi-Mansat, R; Ehrenshaft, M; Mason, R P

    2015-01-01

    Free radicals contribute to the pathogenesis of diabetic cardiomyopathy. We present a method for in vivo observation of free radical events within murine diabetic cardiomyopathy. This study reports on in vivo imaging of protein/lipid radicals using molecular MRI (mMRI) and immuno-spin trapping (IST) in diabetic cardiac muscle. To detect free radicals in diabetic cardiomyopathy, streptozotocin (STZ)-exposed mice were given 5,5-dimethyl-pyrroline-N-oxide (DMPO) and administered an anti-DMPO probe (biotin-anti-DMPO antibody-albumin-Gd-DTPA). For controls, non-diabetic mice were given DMPO (non-disease control), and administered an anti-DMPO probe; or diabetic mice were given DMPO but administered a non-specific IgG contrast agent instead of the anti-DMPO probe. DMPO administration started at 7 weeks following STZ treatment for 5 days, and the anti-DMPO probe was administered at 8 weeks for MRI detection. MRI was used to detect a significant increase (p radicals in cardiac tissue than non-diabetic mice.

  12. Molecular cytogenetic analysis of human blastocysts andcytotrophoblasts by multi-color FISH and Spectra Imaging analyses

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Jingly F.; Ferlatte, Christy; Baumgartner, Adolf; Jung,Christine J.; Nguyen, Ha-Nam; Chu, Lisa W.; Pedersen, Roger A.; Fisher,Susan J.; Weier, Heinz-Ulrich G.

    2006-02-08

    Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing technologies to score all 24 chromosomes in single cells within a 3 day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found aneuploidy, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

  13. Ertragsbildung und Konkurrenzverhalten perennierender Körnerfruchtarten in Rein- und Mischbeständen auf marginalen Standorten

    OpenAIRE

    Weik, Lena

    2002-01-01

    Der Anbau perennierender Körnerfrüchte in Rein- und Mischbeständen auf marginalen Ackerstandorten wurde als alternativer Ansatz zur Erhaltung dieser Flächen untersucht. Die zentralen Fragen lauteten: - Welches Potential zur Bildung von Spross- und von Korntrockenmasse weisen die Arten auf marginalen Standorten auf? - Sind die untersuchten Arten auf marginalen Standorten perennierfähig? - Wie weit sind die Konkurrenzverhältnisse in Mischbeständen perennierender Körnerfruchtarten mitte...

  14. Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery.

    Science.gov (United States)

    Ferrara, Katherine W; Borden, Mark A; Zhang, Hua

    2009-07-21

    Ultrasound pressure waves can map the location of lipid-stabilized gas micro-bubbles after their intravenous administration in the body, facilitating an estimate of vascular density and microvascular flow rate. Microbubbles are currently approved by the Food and Drug Administration as ultrasound contrast agents for visualizing opacification of the left ventricle in echocardiography. However, the interaction of ultrasound waves with intravenously-injected lipid-shelled particles, including both liposomes and microbubbles, is a far richer field. Particles can be designed for molecular imaging and loaded with drugs or genes; the mechanical and thermal properties of ultrasound can then effect localized drug release. In this Account, we provide an overview of the engineering of lipid-shelled microbubbles (typical diameter 1000-10 000 nm) and liposomes (typical diameter 65-120 nm) for ultrasound-based applications in molecular imaging and drug delivery. The chemistries of the shell and core can be optimized to enhance stability, circulation persistence, drug loading and release, targeting to and fusion with the cell membrane, and therapeutic biological effects. To assess the biodistribution and pharmacokinetics of these particles, we incorporated positron emission tomography (PET) radioisotopes on the shell. The radionuclide (18)F (half-life approximately 2 h) was covalently coupled to a dipalmitoyl lipid, followed by integration of the labeled lipid into the shell, facilitating short-term analysis of particle pharmacokinetics and metabolism of the lipid molecule. Alternately, labeling a formed particle with (64)Cu (half-life 12.7 h), after prior covalent incorporation of a copper-chelating moiety onto the lipid shell, permits pharmacokinetic study of particles over several days. Stability and persistence in circulation of both liposomes and microbubbles are enhanced by long acyl chains and a poly(ethylene glycol) coating. Vascular targeting has been demonstrated with

  15. Kelvinsondenmikroskopie an organischen Dünnschicht-Halbleitern:Einfluss der Schichtprozessierung auf elektrische, optische und morphologische Eigenschaften organischer Solarzellen

    OpenAIRE

    Madena, Thomas

    2011-01-01

    Im Rahmen dieser Arbeit erfolgte eine umfassende Untersuchung des Einflusses herstellungsbedingter Unterschiede auf die elektrischen und optischen Eigenschaften organischer BHJ-Solarzellen. Die Ergebnisse der elektrischen und optischen Charakterisierung wurden mit den kraftmikroskopischen Analysen der Halbleiterschichten verglichen und auf mögliche Zusammenhänge untersucht. Die Untersuchungen erfolgten an organischen Halbleitermischschichten, hergestellt auf Basis des Polymer-Fulleren-Gemisch...

  16. Measuring changes in chemistry, composition, and molecular structure within hair fibers by infrared and Raman spectroscopic imaging

    Science.gov (United States)

    Zhang, Guojin; Senak, Laurence; Moore, David J.

    2011-05-01

    Spatially resolved infrared (IR) and Raman images are acquired from human hair cross sections or intact hair fibers. The full informational content of these spectra are spatially correlated to hair chemistry, anatomy, and structural organization through univariate and multivariate data analysis. Specific IR and Raman images from untreated human hair describing the spatial dependence of lipid and protein distribution, protein secondary structure, lipid chain conformational order, and distribution of disulfide cross-links in hair protein are presented in this study. Factor analysis of the image plane acquired with IR microscopy in hair sections, permits delineation of specific micro-regions within the hair. These data indicate that both IR and Raman imaging of molecular structural changes in a specific region of hair will prove to be valuable tools in the understanding of hair structure, physiology, and the effect of various stresses upon its integrity.

  17. MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

    Directory of Open Access Journals (Sweden)

    Fabiana A Caetano

    2015-12-01

    Full Text Available Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

  18. Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovascularization as well as Tumor Cells in Molecular Tumor Imaging

    Institute of Scientific and Technical Information of China (English)

    Xia Lu; Ping Yan; Rong-fu Wang; Meng Liu; Ming-ming Yu; Chun-li Zhang

    2012-01-01

    Objective:To explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys,tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2).Methods:The tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs.Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 (131I-tRRL).The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro.Whether VEGFR-2 is the binging site of tRRL was investigated.Biodistribution and single-photon emission computed tomography (SPECT) imaging of 131I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.Results:In vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells.VEGFR-2,which is highly expressed on TDECs,was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium.131I-tRRL mainly accumulated in tumors in vivo,not other organs at 24 h after injection.SPECT imaging with 131I-tRRL clearly visualized tumors in nude mice,especially at 24 h.Conclusion:Radioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization,and may be a promising candidate for tumor radioimmunotherapeutic carrier.

  19. Establishment of clonal MIN-O transplant lines for molecular imaging via lentiviral transduction & in vitro culture.

    Directory of Open Access Journals (Sweden)

    David L Boucher

    Full Text Available As the field of molecular imaging evolves and increasingly is asked to fill the discovery and validation space between basic science and clinical applications, careful consideration should be given to the models in which studies are conducted. The MIN-O mouse model series is an established in vivo model of human mammary precancer ductal carcinoma in situ with progression to invasive carcinoma. This series of transplant lines is propagated in vivo and experiments utilizing this model can be completed in non-engineered immune intact FVB/n wild type mice thereby modeling the tumor microenvironment with biological relevance superior to traditional tumor cell xenografts. Unfortunately, the same qualities that make this and many other transplant lines more biologically relevant than standard cell lines for molecular imaging studies present a significant obstacle as somatic genetic re-engineering modifications common to many imaging applications can be technically challenging. Here, we describe a protocol for the efficient lentiviral transduction of cell slurries derived from precancerous MIN-O lesions, in vitro culture of "MIN-O-spheres" derived from single cell clones, and the subsequent transplantation of these spheres to produce transduced sublines suitable for optical imaging applications. These lines retain the physiologic and pathologic properties, including multilineage differentiation, and complex microanatomic interaction with the host stroma characteristic of the MIN-O model. We also present the in vivo imaging and immunohistochemical analysis of serial transplantation of one such subline and detail the progressive multifocal loss of the transgene in successive generations.

  20. Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans.

    Science.gov (United States)

    Nikolaus, Susanne; Antke, Christina; Kley, Konstantin; Poeppel, Thorsten D; Hautzel, Hubertus; Schmidt, Daniela; Müller, Hans-Wilhelm

    2007-01-01

    Dopaminergic synaptic function may be assessed either at the presynaptic terminal or at the postsynaptic binding sites using molecular in vivo imaging methods. Apart from the density of binding sites, parameters such as alterations in dopamine synthesis, dopamine storage or dopamine release can be quantified either by application of specific radiotracers or by assessing the competition between the exogenous radioligand and endogenous dopamine. Investigations of humans in both clinical and experimental settings have yielded evidence that disturbances of dopaminergic function may be associated with numerous neurological and psychiatric conditions, among which are movement disorders, schizophrenia, attention-deficit hyperactivity disorder, depression and drug abuse. This article gives an overview of those studies, which so far have been performed on dopaminergic neurotransmission in humans using in vivo imaging methods. We focus on disease-related deficiencies within the functional entity of the dopaminergic synapse. Taken together, in vivo findings yield evidence of presynaptic dysfunctions in Parkinson's disease with decreases in striatal dopamine synthesis, dopamine storage, dopamine release and dopamine transporter binding. In contrast, 'Parkinson plus' syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies) are characterized by both pre- and postsynaptic deficiencies with reductions in striatal dopamine synthesis, dopamine storage, dopamine release, and dopamine transporter, as well as D, and D, receptor binding. In patients with Huntington's disease, postsynaptic dysfunctions with reductions of striatal D1 and D2 receptor binding have become apparent, whereas attention-deficit/ hyperactivity disorder is mainly characterized by presynaptic deficits with increases in dopamine transporter binding. Interestingly, findings are also consistent with respect to drug abuse: cocaine, amphetamine

  1. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    Science.gov (United States)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  2. Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chiriaco, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Ragusa, Andrea [National Nanotechnology Laboratory of CNR-NANO (Italy); Sbenaglia, Enzo Antonio; Dipaola, Lucia [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Casciaro, Sergio, E-mail: sergio.casciaro@cnr.it [Istituto di Fisiologia Clinica (CNR-IFC) c/o Campus Universitario Ecotekne, Consiglio Nazionale delle Ricerche (Italy)

    2013-07-15

    Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

  3. Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

    International Nuclear Information System (INIS)

    Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5–5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low

  4. Improved characterization of molecular phenotypes in breast lesions using 18F-FDG PET image homogeneity

    Science.gov (United States)

    Cao, Kunlin; Bhagalia, Roshni; Sood, Anup; Brogi, Edi; Mellinghoff, Ingo K.; Larson, Steven M.

    2015-03-01

    Positron emission tomography (PET) using uorodeoxyglucose (18F-FDG) is commonly used in the assessment of breast lesions by computing voxel-wise standardized uptake value (SUV) maps. Simple metrics derived from ensemble properties of SUVs within each identified breast lesion are routinely used for disease diagnosis. The maximum SUV within the lesion (SUVmax) is the most popular of these metrics. However these simple metrics are known to be error-prone and are susceptible to image noise. Finding reliable SUV map-based features that correlate to established molecular phenotypes of breast cancer (viz. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression) will enable non-invasive disease management. This study investigated 36 SUV features based on first and second order statistics, local histograms and texture of segmented lesions to predict ER and PR expression in 51 breast cancer patients. True ER and PR expression was obtained via immunohistochemistry (IHC) of tissue samples from each lesion. A supervised learning, adaptive boosting-support vector machine (AdaBoost-SVM), framework was used to select a subset of features to classify breast lesions into distinct phenotypes. Performance of the trained multi-feature classifier was compared against the baseline single-feature SUVmax classifier using receiver operating characteristic (ROC) curves. Results show that texture features encoding local lesion homogeneity extracted from gray-level co-occurrence matrices are the strongest discriminator of lesion ER expression. In particular, classifiers including these features increased prediction accuracy from 0.75 (baseline) to 0.82 and the area under the ROC curve from 0.64 (baseline) to 0.75.

  5. Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles.

    Directory of Open Access Journals (Sweden)

    Giorgio Tasca

    Full Text Available BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI we observed that T2-short tau inversion recovery (T2-STIR sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. METHODS: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense. Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. RESULTS: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. CONCLUSIONS: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis

  6. Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

    Science.gov (United States)

    Swy, Eric R.; Schwartz-Duval, Aaron S.; Shuboni, Dorela D.; Latourette, Matthew T.; Mallet, Christiane L.; Parys, Maciej; Cormode, David P.; Shapiro, Erik M.

    2014-10-01

    Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.Reports of molecular and cellular imaging using

  7. 分子成像与肿瘤靶向治疗%Molecular imaging and tumor targeted therapy

    Institute of Scientific and Technical Information of China (English)

    孙夕林; 韩兆国; 吴泳仪; 申宝忠

    2016-01-01

    肿瘤关键分子靶点的异常表达(表达水平和表达状态)与分子靶向治疗反应、治疗效果及预后密切相关。因此,精准评价肿瘤关键分子表达水平和表达状态,无论在肿瘤分子靶向治疗开展前、过程中以及治疗后均显得尤为关键。分子成像可以无创、实时而全面地对肿瘤关键靶点的表达水平及表达状态进行定性、定量研究,对筛选优势人群、指导治疗、判断预后具有重大意义。本文简述基于不同分子探针的分子成像技术在肿瘤靶向治疗过程中的应用,对比分析分子成像在靶向治疗中的价值,以期有益于新型治疗策略的开发。%The abnormal expression (level and status) of the key molecular targets of tumors is related to molecular targeted therapy response, effect, and prognosis. Therefore, the expression level and status of key molecular targets of tumors must be accurately evalu-ated, regardless of the status before, during, and after receiving targeted therapy. Molecular imaging is a non-invasive method used for qualitative and quantitative research on key molecular targets of tumor in vivo and in real-time. This technique is also employed to screen treatment beneficiaries, guide therapy, and evaluate prognosis. This paper reviews the application progress of molecular imag-ing using various probes in cancer targeted therapy. The clinical value of molecular imaging in tumor targeted therapy is further ana-lyzed to promote the development of novel targeted therapy for tumors.

  8. Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

    OpenAIRE

    HONARVAR, HADIS; Jokilaakso, Nima; Andersson, Karl; Malmberg, Jennie; Rosik, Daniel; Orlova, Anna; Karlstrom, Amelie Eriksson; Tolmachev, Vladimir; Jarver, Peter

    2013-01-01

    Introduction Affibody molecules, small scaffold proteins, have demonstrated an appreciable potential as imaging probes. Affibody molecules are composed of three alpha-helices. Helices 1 and 2 are involved in molecular recognition, while helix 3 provides stability. The size of Affibody molecules can be reduced by omitting the third alpha-helix and cross-linking the two remaining, providing a smaller molecule with better extravasation and quicker clearance of unbound tracer. The goal of this st...

  9. Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

    OpenAIRE

    Gruszecki, Wieslaw I.; Luchowski, Rafał; Gagoś, Mariusz; Arczewska, Marta; Sarkar, Pabak; Hereć, Monika; Myśliwa-Kurdziel, Beata; Strzałka, Kazimierz; Gryczynski, Ignacy; Gryczynski, Zygmunt

    2009-01-01

    Abstract Amphotericin B (AmB) is a life-saving polyene antibiotic used to treat deep-seated mycotic infections. Both the mode of therapeutic action as well as toxic side effects are directly dependent on molecular organization of the drug. Binding of AmB to lipid monolayers formed with dipalmitoylphosphatidylcholine, pure and containing 40 mol% cholesterol or ergosterol, the sterols of human and fungi respectively, has been examined by means of Fluorescence Lifetime Imaging Microsc...

  10. Molecular MR Imaging for Visualizing ICAM-1 Expression in the Inflamed Synovium of Collagen-Induced Arthritic Mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Il [Gyeongsang National University, Jinju (Korea, Republic of); Lee, Sang Yong; Jang, Kyu Yun; Yoo, Wan Hee [Chonbuk National University, Jeonju (Korea, Republic of); Yoon, Kwon Ha [Wonkwang University School of Medicine, Iksan (Korea, Republic of); Choi, Kyu Sil [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sang Hyon; Choi, Tae Hyun [Dongsan Medical Center, Keimyung University, Daegu (Korea, Republic of); Park, Jin Gyoon [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2009-10-15

    To determine the utility of intercellular adhesion molecule (ICAM)-1 antibody-conjugated gadolinium diethylenetriaminepentaacetic acid (Gd-DTPAanti- ICAM-1) as a targeted contrast agent for the molecular magnetic resonance imaging (MRI) in collagen-induced arthritis (CIA). Three groups of mice were used: non-arthritic normal, CIA mice in both the early inflammatory and chronic destructive phases. The MR images of knee joints were obtained before and after injection of Gd-DTPA-anti- ICAM-1, Gd-DTPA, and Gd-DTPA-Immunoglobulin G (Ig G) and were analyzed quantitatively. The patterns of enhancement on the MR images were compared with the histological and immunohistochemical ICAM-1 staining. The images obtained after injection of Gd-DTPA-anti-ICAM-1 displayed gradually increasing signal enhancement from the moment following injection (mean {+-} standard deviation [SD]: 424.3 {+-} 35.2, n = 3) to 24 hours (532 {+-} 11.3), rather than on pre-enhanced images (293 {+-} 37.6) in the early inflammatory phase of CIA mice. However, signal enhancement by Gd-DTPA and Gd- DTPA-IgG disappeared after 80 minutes and 24 hours, respectively. In addition, no significant enhancement was seen in the chronic destructive phase of CIA mice, even though they also showed inflammatory changes on T2-weighted MR images. ICAM-1 expression was demonstrated in the endothelium and proliferating synovium of the early inflammatory phase of CIA mice, but not in the chronic destructive phase. Molecular MRI with Gd-DTPA-anti-ICAM-1 displays specific images targeted to ICAM-1 that is expressed in the inflamed synovium of CIA. This novel tool may be useful for the early diagnosis and differentiation of the various stages of rheumatoid arthritis.

  11. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    An Ruifang; He Dalin; Xue Yan; Wang Shu; Xie Li; Zhao Jun; Wang Xinyang; Yang Lili

    2006-01-01

    Objective To detect the expression of survivin mRNA in cervical cancer cell lines using molecular beacon imaging technology. Methods Human cervical cancer cells (HeLa and SiHa) and human fetal lung fibroblast HFL-I were cultured in vitro. After adding 100 nmol/L survivin mRNA molecular beacon, the fluorescent signals were observed under fluorescent microscope. The expressions of survivin in cervical cancer cells and HFL-I cell were examined by immunocytochemical streptravidin-biothin peroxidase (SP) assay at the same time. Results Two kinds of survivin mRNA molecular beacon, with different color fluorescence, had strong fluorescent signal in cervical cancer cell lines, and the signal in SiHa cell line was stronger, but these signals were not found in HFL-I ; Immunocytochemical staining of positive survivin was located in the cytoplasm of cervical cancer cell lines HeLa and SiHa, whereas, no expression of survivin was detected in HFL-I cell line. Conclusion The technology of molecular beacon imaging can be used to detect the expression of survivin mRNA in viable cells successfully, and may provide a new approach to the diagnosis of early stage cervical cancer and the following-up in the clinic.

  12. Complementary optical and nuclear imaging of caspase-3 activity using combined activatable and radio-labeled multimodality molecular probe

    Science.gov (United States)

    Lee, Hyeran; Akers, Walter J.; Cheney, Philip P.; Edwards, W. Barry; Liang, Kexian; Culver, Joseph P.; Achilefu, Samuel

    2009-07-01

    Based on the capability of modulating fluorescence intensity by specific molecular events, we report a new multimodal optical-nuclear molecular probe with complementary reporting strategies. The molecular probe (LS498) consists of tetraazacyclododecanetetraacetic acid (DOTA) for chelating a radionuclide, a near-infrared fluorescent dye, and an efficient quencher dye. The two dyes are separated by a cleavable peptide substrate for caspase-3, a diagnostic enzyme that is upregulated in dying cells. LS498 is radiolabeled with 64Cu, a radionuclide used in positron emission tomography. In the native form, LS498 fluorescence is quenched until caspase-3 cleavage of the peptide substrate. Enzyme kinetics assay shows that LS498 is readily cleaved by caspase-3, with excellent enzyme kinetic parameters kcat and KM of 0.55+/-0.01 s-1 and 1.12+/-0.06 μM, respectively. In mice, the initial fluorescence of LS498 is ten-fold less than control. Using radiolabeled 64Cu-LS498 in a controlled and localized in-vivo model of caspase-3 activation, a time-dependent five-fold NIR fluorescence enhancement is observed, but radioactivity remains identical in caspase-3 positive and negative controls. These results demonstrate the feasibility of using radionuclide imaging for localizing and quantifying the distribution of molecular probes and optical imaging for reporting the functional status of diagnostic enzymes.

  13. Dendrimersomes: a new vesicular nano-platform for MR-molecular imaging applications.

    Science.gov (United States)

    Filippi, Miriam; Martinelli, Jonathan; Mulas, Gilberto; Ferraretto, Marisa; Teirlinck, Eline; Botta, Mauro; Tei, Lorenzo; Terreno, Enzo

    2014-04-01

    A new class of nanovesicles formed by the self-assembly of amphiphilic Janus dendrimers, dendrimersomes, loaded with hydrophilic or amphiphilic magnetic resonance imaging chelates shows promising properties as a novel, efficient and versatile nanoplatform for biomedical imaging. PMID:24553970

  14. A matter of collection and detection for intraoperative and noninvasive near-infrared fluorescence molecular imaging: To see or not to see?

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Banghe; Rasmussen, John C.; Sevick-Muraca, Eva M., E-mail: Eva.Sevick@uth.tmc.edu [Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas 77030 (United States)

    2014-02-15

    Purpose: Although fluorescence molecular imaging is rapidly evolving as a new combinational drug/device technology platform for molecularly guided surgery and noninvasive imaging, there remains no performance standards for efficient translation of “first-in-humans” fluorescent imaging agents using these devices. Methods: The authors employed a stable, solid phantom designed to exaggerate the confounding effects of tissue light scattering and to mimic low concentrations (nM–pM) of near-infrared fluorescent dyes expected clinically for molecular imaging in order to evaluate and compare the commonly used charge coupled device (CCD) camera systems employed in preclinical studies and in human investigational studies. Results: The results show that intensified CCD systems offer greater contrast with larger signal-to-noise ratios in comparison to their unintensified CCD systems operated at clinically reasonable, subsecond acquisition times. Conclusions: Camera imaging performance could impact the success of future “first-in-humans” near-infrared fluorescence imaging agent studies.

  15. Heidelberger Universitätsrede 2007: Klimawandel... auf beiden Seiten des Atlantiks

    OpenAIRE

    Arthur, Michael

    2007-01-01

    Welche wirtschaftlichen Folgen etwa auf uns zukommen könnten, hat der vor einem Jahr von der britischen Regierung in Auftrag gegebene Bericht von Lord Nicholas Stern, dem ehemaligen Chefökonomen der Weltbank, eindringlich vor Augen geführt. Ausgehend von verschiedenen Modellrechnungen schätzt er die Kosten und Risiken im schlimmsten Falle auf bis zu 20 Prozent des globalen Bruttoinlandsprodukts jährlich. Basierend auf diesem Bericht wird der Britische Botschafter in Berlin, Sir Michael Arthur...

  16. Ein nicht-erwerbszentrierter Blick auf die Geschlechterverhältnisse in der DDR und Ostdeutschland

    Directory of Open Access Journals (Sweden)

    Sylka Scholz

    2001-11-01

    Full Text Available Im Mittelpunkt des Buches von Susanne Stolt steht die Frage nach alltäglichen Geschlechterbeziehungen in Ostdeutschland nach der Wende und der individuellen Suche nach Anerkennung von Männern und Frauen. Theoretisch stützt Stolt sich dabei v.a. auf den psychoanalytisch geprägten Ansatz von Jessica Benjamin mit der Fokussierung auf das Anerkennungsproblem und empirisch auf qualitative Interviews von Frauen und Ehepaaren. Sie distanziert sich von „erwerbszentrierten Perspektiven“, die die Dominanz des Erwerbssystems und die Abwertung von Fürsorgearbeit fortschreiben und damit die in die Erwerbssphäre eingeschriebene männliche Herrschaft reproduzieren.

  17. Auswirkungen regionaler Freihandelsabkommen auf deutsche und europäische Agrarmärkte

    OpenAIRE

    Pelikan, Janine; Banse, Martin

    2014-01-01

    Das vorliegende Thünen Working Paper basiert auf einer Anfrage des BMEL, Referat 621, an das Thünen-Institut für Marktanalyse bzgl. einer Analyse möglicher Auswirken der derzeit in der EU diskutierten Freihandelsabkommen mit den USA und Japan. Der Schwerpunkt dieser Untersuchung, die mit dem allgemeinen Gleichgewichtsmodell MAGNET durchgeführt wurde, liegt auf der Folgenabschätzung des Abbaus der tarifären Protektion auf die europäischen und deutschen Agrarmärkte. Neben den direkten Wirkungen...

  18. Progresses in molecular imaging of prostate cancer%前列腺癌的分子影像学进展

    Institute of Scientific and Technical Information of China (English)

    范校周; 郭燕丽

    2013-01-01

    前列腺癌是严重威胁男性健康的疾病.分子影像学的出现,从一个全新角度为前列腺癌的早期诊断与治疗提供了可能,新的前列腺癌标志物也不断出现.本文对当前分子影像学技术,包括核素显像、MRI、超声和光学技术在前列腺癌诊治中的应用进展进行回顾.%Prostate cancer is a serious threat to male health, and the development of molecular imaging provides the possibility for early diagnosis and treatment of prostate cancer from a new perspective. With the emerging markers of prostate cancer, the current modalities of molecular imaging, including radionuclide imaging, MRI, ultrasound and optical imaging in diagnosis and treatment of prostate cancer were reviewed in this article.

  19. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

    Science.gov (United States)

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner. PMID:26722379

  20. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring.

    Science.gov (United States)

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner. PMID:26722379

  1. In Vivo Molecular Imaging to Diagnose and Subtype Tumors through Receptor-Targeted Optically Labeled Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Yoshinori Koyama

    2007-12-01

    Full Text Available Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431 and HER-2 (NIH3T3/HER2+, or interleukin-2 receptor α-subunit receptor (IL-2Rα; SP2/Tac. After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targeting HER-1, trastuzumab-Cy7 (HER-2, daclizumab-AIexaFluor700 (IL-2Ra. Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, deep red. Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2+, SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022. In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.

  2. 19F molecular MR imaging for detection of brain tumor angiogenesis: in vivo validation using targeted PFOB nanoparticles

    International Nuclear Information System (INIS)

    Molecular imaging with magnetic resonance imaging (MRI) targeted contrast agents has emerged as a promising diagnostic approach in cancer research to detect associated bio-markers. In this work, the potential of 19F MRI was investigated to detect angiogenesis with αvβ3-targeted perfluoro-octylbromide nanoparticles (PFOB NP) in a U87 glioblastoma mouse model at 7 Tesla. Mice were injected intravenously with targeted or non-targeted NP and 19F images were immediately acquired for 90 min using a PFOB-dedicated MRI sequence. Mice infused with targeted NP exhibited higher concentrations in tumors than mice of the control group, despite the presence of nonspecific signal originating from the blood. Imaging results were corroborated by histology and fluorescence imaging, suggesting specific binding of targeted NP to αvβ3 integrin. Two other groups of mice were injected 24 h before imaging to allow blood clearance but no significant differences were found between both groups, probably due to a loss of specificity of PFOB NP. This is the first demonstration of the ability of 19F MRI to detect αvβ3 -integrin endothelial expression in brain tumors in vivo. (authors)

  3. Near-field infrared imaging of molecular changes in cholesteryl oleate by free electron laser infrared ablation

    Science.gov (United States)

    Masaki, Tatsuhiro; Goto, Kazuya; Inouye, Yasushi; Kawata, Satoshi

    2004-01-01

    We have applied infrared near-field scanning optical microscopy (IR-NSOM) to enable evaluation of detailed molecular changes in cholesteryl oleate, a primary cause of arteriosclerosis. In our IR-NSOM, a wide wavelength range of 2.9-6.7 μm is achieved by use of an optical parametric amplifier and an apertured cantilever. IR irradiation from a free-electron laser (FEL) tuned to a 5.75 μm wavelength induced molecular structural changes and caused cholesteryl oleate to decompose to cholesterol and fatty acids in the FEL irradiated areas. The IR-NSOM images at two different wavelengths, 5.75 and 5.3 μm, with a 2 μm apertured cantilever probe successfully identified areas of molecular change in cholesteryl oleate beyond the diffraction limit of IR microspectroscopy. In-depth molecular structure changes were also evaluated by the IR-NSOM and we demonstrated that the FEL irradiation induced subsurface molecular structure changes throughout cholesteryl oleate in the irradiated areas.

  4. Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies

    Energy Technology Data Exchange (ETDEWEB)

    Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

    2008-03-15

    Rising life-expectancy in the modern society has resulted in a rapidly growing prevalence of dementia, particularly of Alzheimer's disease (AD). Dementia turns into one of the most common age-related disorders with deleterious consequences for the concerned patients and their relatives, as well as worrying effects on the socio-economic systems. These facts justify strengthened scientific efforts to identify the pathologic origin of dementing disorders, to improve diagnosis, and to interfere therapeutically with the disease progression. In the recent years, remarkable progress has been made concerning the identification of molecular mechanisms underlying the pathology of neurodegenerative disorders. Growing evidence indicates that a common basis of many neurodegenerative dementias can be found in increased production, misfolding and pathological aggregation of proteins, such as ss-amyloid, tau protein, a-synuclein, or the recently described ubiquitinated TDP-43. This progressive insight in pathological processes is paralleled by the development of new therapeutic approaches. However, the exact contribution or mechanism of different pathologies with regard to the development of disease is not yet sufficiently clear. Considerable overlap of pathologies has been documented in different types of clinically defined dementias post mortem, and it has been difficult to correlate post mortem histopathology data with disease-expression during life. Molecular imaging procedures may play a valuable role to circumvent this limitation. In general, methods of molecular imaging have recently experienced an impressive advance, with numerous new and improved technologies emerging. These exciting tools may play a key role in the future regarding the evaluation of pathomechanisms, preclinical evaluation of new diagnostic procedures in animal models, selection of patients for clinical trials, and therapy monitoring. In this overview, molecular key pathologies, which are currently

  5. Near-Infrared Fluorescence Enhanced (NIR-FE) Molecular Imaging of Live Cells on Gold Substrates

    CERN Document Server

    Hong, Guosong; Welsher, Kevin; Chen, Zhuo; Robinson, Joshua T; Wang, Hailiang; Zhang, Bo; Dai, Hongjie

    2011-01-01

    Low quantum yields of near infrared (NIR) fluorophores have limited their capabilities as imaging probes in a transparent, low background imaging window. Here for the first time we reported near-infrared fluorescence enhance (NIR-FE) cell imaging using nanostructured Au substrate, which was employed as a general platform for both single-walled carbon nanotubes (SWNTs) and organic fluorescent labels in the NIR region. Fluorescence intensity, as well as cell targeting specificity, was greatly improved by this novel imaging technique. With NIR-FE imaging, we were able to image SWNT-stained cells at short exposure time of 300ms, and push the detectable limit of SWNT staining of cells down to an ultralow concentration of ~50 pM. Further, different degrees of fluorescence enhancement for endocytosed, intracellular SWNTs vs. nanotubes on the cell membrane at the cell/gold interface were observed, suggesting the possibility of using this technique to track the transmembrane behavior of NIR fluorophores.

  6. Introduction to the physics of molecular imaging with radioactive tracers in small animals.

    Science.gov (United States)

    King, Michael A; Pretorius, P Hendrik; Farncombe, Troy; Beekman, Freek J

    2002-01-01

    Recent advances have greatly enhanced the three-dimensional (3D) imaging of radioactive tracers in living animals. this article introduces the physics of imaging behind the imaging methods. The article first discusses the selection of the radiation emitted from the tracer and then the process of tomographic reconstruction or how 3D images are made from imaging around the outside of the animal. The technique of single photon emission computed tomography (SPECT) in which the detection of one X-ray or gamma ray at a time is employed for image formation is then described. Finally, positron emission tomography (PET) which relies on the simultaneous detection of the pair of gamma-rays formed when the positron annihilates is presented.

  7. Einflüsse von Pimecrolimus und Triamcinolonacetonid auf die epidermale Hautbarriere bei atopischer Dermatitis

    OpenAIRE

    Weppner, Merle

    2016-01-01

    Untersuchung der epidermalen Hautbarriere durch Bestimmung klinischer Parameter, biophysikalischer Parameter (Transepidermaler Wasserverlust, Hauthydratation, Integrität des St. corneum), lichtmikroskopischer Analysen (Immunhistochemie auf epidermale Proliferations- und Differenzierungsmarker) sowie elektronenmikroskopischer Analysen (Lamellenkörperchen/ lamellar bodies).

  8. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging.

    Directory of Open Access Journals (Sweden)

    Sarah J Moore

    Full Text Available BACKGROUND: Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI from squash seeds, the Agouti-related protein (AgRP neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx, an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. METHODOLOGY/PRINCIPAL FINDINGS: We used a rational loop-grafting approach to engineer AgTx variants that bound to αvβ3 integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. CONCLUSIONS/SIGNIFICANCE: In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using

  9. Market analysis offshore wind energy; Marktanalyse Windenergie auf See

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-07-01

    will implement against the background of high Investment volumes and technical challenges each but usually only a manageable number of projects in Europe per year. The various legal requirements in the area of offshore wind energy, and in particular planning, Licensing and network side should be further coordinated and more interlinked. Considerations are also European regulations and the support systems of our European neighbors. [German] Der Nordsee kommt im Vergleich zur Ostsee aufgrund des verfuegbaren Flaechenangebots ein deutlich groesseres Potenzial zu. Im Vergleich zur Nordsee liegen die erschliessbaren Potenziale der Ostsee allerdings deutlich kuestennaeher, was nicht nur beim Netzanschluss sondern auch beim Bau und Betrieb der Anlagen Effizienzvorteile haben kann. Noch ist unklar, ob die verfuegbaren Flaechen im Kuestenmeer der Ostsee in relevanten Groessenordnung erweitert werden koennen. Der entsprechende Raumplanungsprozess wurde im Jahr 2014 durch Mecklenburg-Vorpommern angestossen. Die Analyse der im Bundesfachplan Offshore festgelegten Cluster, die der Offshore-Netzentwicklungsplan in Zonen fuer die Nord- und Ostsee (1-5) strukturiert, zeigt, dass zumindest in der Ausbauphase bis 2025, ggf. auch bis 2030 die kuestennaeheren Zonen 1 und 2 in Nord- und Ostsee ein ausreichendes Flaechenpotential bieten und zugleich im Hinblick auf einen effizienten und strukturierten Netzausbau erschlossen werden sollten. Der Ausbaupfad bis 2020 ermoeglicht die von der Industrie in Aussicht gestellten Kostendegressionen in Hoehe von ueber 30 Prozent. Die bereits heute erkennbaren Kostensenkungen muessen insofern im Rahmen der Erarbeitung des Ausschreibungsdesigns beruecksichtigt werden. Dies gilt auch fuer die Frage eines optimalen Park- und Anlagendesigns aus energiewirtschaftlicher Sicht. Neben jeweils projektinternen Schwierigkeiten auf Netz- wie auf Windparkseite liegen erhebliche Schnittstellenprobleme zwischen Windpark und Netzanschluss. Dies liegt u.a. an den

  10. Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging.

    Science.gov (United States)

    Hasegawa, Sumitaka; Koshikawa-Yano, Michiko; Saito, Shigeyoshi; Morokoshi, Yukie; Furukawa, Takako; Aoki, Ichio; Saga, Tsuneo

    2011-05-01

    Malignant mesothelioma (MM) is a fatal malignancy with a rapidly increasing incidence in industrialized countries because of the widespread use of asbestos in the past centuries. Early diagnosis of MM is critical for a better prognosis, but this is often difficult because of the lack of disease-specific diagnostic imaging. Here, we report that manganese-enhanced magnetic resonance imaging (MEMRI) represents a promising approach for a more selective mesothelioma imaging by monitoring a high-level expression of manganese-superoxide dismutase (Mn-SOD), which is observed in many MM. We found that most human MM cells overexpressed Mn-SOD protein compared with human mesothelial cells and that NCI-H226 human MM cells highly expressed Mn-SOD and augmented Mn accumulation when loaded with manganese chloride (MnCl(2)). The cells showed marked T(1)-signal enhancement on in vitro MRI after incubation with MnCl(2) because of the T(1) shortening effect of Mn(2+). H226 subcutaneous tumor was preferentially enhanced compared with a lung adenocarcinoma cell tumor and another human MM cell tumor in MnCl(2)-enhanced T(1)-weighted MR image (T(1)WI), correlating with their respective Mn-SOD expression levels. Moreover, in a more clinically relevant setting, H226 xenografted pleural tumor was markedly enhanced and readily detected by MEMRI using manganese dipyridoxyl diphosphate (MnDPDP), a clinically used contrast agent, as well as MnCl(2). Therefore, we propose that MEMRI can be a potentially powerful method for noninvasive detection of MM, with high spatial resolution and marked signal enhancement, by targeting Mn-SOD. PMID:20617513

  11. A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

    Science.gov (United States)

    Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

    2016-04-01

    The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

  12. Besitzt der Mensch einen freien Willen? Antwort auf Libets Herausforderung

    Directory of Open Access Journals (Sweden)

    Josef Seifert

    2013-10-01

    Full Text Available Auf die entscheidende Frage nach der Existenz menschlicher Willensfreiheit gibt Libet auf Grund empirischer Experimente mit der Freiheit eine partiell negative philosophische Antwort: es gibt nur „negative“ Vetofreiheit; positive Handlungen werden vom Gehirn verursacht. Von Libets philosophischer Interpretation seiner experimentellen Ergebnisse, der zufolge der Mensch keine positive, sondern nur eine „negative“ Vetofreiheit besitze, soll gezeigt werden, daß (a im Licht anderer wissenschaftlicher Forschungsergebnisse ihre empirische Basis unzureichend und irreführend scheint, sie (b eine weder neurowissenschaftlich noch philosophisch gesehen solide Methodologie verwendet, insbesondere was Zeitmessungen bewußter Akte angeht; (c primär philosophischer Natur ist, (d eine insbesondere wegen einer behavioristischen Handlungstheorie und einer fehlenden Analyse der vielfältigen personalen Akte, welche willentlicher Bewegung vorausgehen, des Willensaktes selbst, und der „Positivität“ „negativer Freiheit“ in philosophischer Hinsicht eine äußerst unzureichende Basis hat und (e widersprüchlich ist. Abstract of Do humans possess free will? Answer to Libet’s challenge Based on his “empirical experiments with free will,” Libet gives a partially negative philosophical answer to the crucial question about the existence of human free will. According to Libet’s philosophical interpretation of his experimental results, humans only possess „negative” (veto- free will; “positive volitional actions” are caused by the brain. The paper seeks to show that: a in the light of other results of scientific research even the empirical basis of this claim seems to be insufficient and misleading; (b Libet uses a methodology that is neither neuroscientifically nor philosophically speaking solid, in particular as to what concerns time measurements of conscious acts; (c his thesis is of primarily philosophical nature; (d and in philosophical

  13. Eigensinnige 'Kunden' : Auswirkungen strenger Zumutbarkeitsregeln auf Langzeitarbeitslose und prekär Beschäftigte

    OpenAIRE

    Dörre, Klaus; Bescherer, Peter; Röbenack, Silk; Schierhorn, Karen

    2008-01-01

    Der Beitrag präsentiert erste Befunde aus dem Teilprojekt "Eigensinnige 'Kunden'. Die Auswirkungen strenger Zumutbarkeit auf die Erwerbsorientierung Arbeitsloser und prekär Beschäftigten" des SFB 580. Hauptsächlich auf eine qualitative Befragung von Beziehern des Arbeitslosengeldes II gestützt, argumentiert der Artikel vor dem Hintergrund der aktuellen underclass-Debatte. Er zeigt, dass es sich bei den Langzeitarbeitslosen keineswegs um Angehörige einer kulturell homogenen Unterschicht handel...

  14. Studien zu Synthese, Charakterisierung und Bewertung von strukturierten Katalysatoren auf Basis karbidabgeleitetem Kohlenstoffs

    OpenAIRE

    Knorr, Tilman

    2013-01-01

    Die vorliegende Arbeit befasst sich mit der Synthese strukturierter Katalysatorsysteme auf der Basis von karbidabgeleitetem Kohlenstoff. Dieser stellt eine Klasse von Kohlenstoffmaterialien dar, die durch Reaktivextraktion des Metalls aus Karbiden bei Temperaturen um 1000 °C synthetisiert werden können. Hierzu werden in der Regel Halogene eingesetzt. Diese Kohlenstoffmaterialien sind mikroporös und weisen enge Porengrößenverteilungen im Ångström-Bereich auf. In dieser Arbeit wurden verschiede...

  15. Untersuchung innermotorischer Einflussgrößen auf die Partikelemission eines Ottomotors mit Direkteinspritzung

    OpenAIRE

    Dageförde, Helge

    2015-01-01

    Die Arbeit befasst sich mit der Ermittlung der Ursachen von Partikelemissionen und der Ableitung von Maßnahmen zu ihrer Reduktion. Dabei spielt die Betrachtung der Gemischbildung eine wesentliche Rolle. Es werden innermotorische optische Untersuchungen an einem Einhubtriebwerk sowie einem Einzylindermotor durchgeführt und mehrere Faktoren auf ihren Einfluss auf die Partikelbildung und -oxidation diskutiert. Die motorischen Untersuchungen werden mit Partikelmessungen im Abgas begleitet.

  16. Die Wirkung flexibler Entgeltkomponenten auf den Arbeitsmarkt unter Berücksichtigung betriebswirtschaftlicher Aspekte

    OpenAIRE

    Schlegtendal, Götz

    2003-01-01

    Untersuchungsgegenstand dieser Arbeit sind die Wirkungen flexibler Entgeltkomponenten (Leistungslohn, Erfolgsbeteiligung, Kapitalbeteiligung) auf der betriebs- und volkswirtschaftlichen Ebene. Ausgangspunkt ist dabei die Analyse der herrschenden Arbeitslosigkeit im Hinblick auf die Ursachen und die Gründe ihrer Verfestigung und Persistenz. Dabei wird festgestellt, dass die existierende Arbeitslosigkeit über verschiedene Theorien erklärt und in mehrere Bestandteile zerlegt werden kann. Ein erh...

  17. Effekte von Noradrenalin und LPS auf die mitochondriale Atmung von Alveolarmakrophagen

    OpenAIRE

    Widmann, Matthias

    2014-01-01

    Hintergrund: Wie bisherige Studien zeigen, ist der Mechanismus, über welchen sowohl Endotoxine als auch Katecholamine in den Regelkreislauf der Mitochondrien eingreifen, sehr komplex. In dieser Studie sollten daher die isolierten Effekte von Noradrenalin und Endotoxinen auf die mitochondriale Atmung von Lungenalveolarmakrophagen der Maus untersucht werden. Methoden: Es wurden 5 Gruppen auf Veränderungen der Atmungsaktivität im gekoppelten sowie maximal entkoppelten Zustand untersucht: eine Ko...

  18. Ekel und 'Natur': zur Übertragung von Grenzen des Selbst auf Grenzen in der Lebensumwelt

    OpenAIRE

    Putzhammer, Simon

    2011-01-01

    "Der Text kann einerseits als Positionsbestimmung in Hinblick auf Theorien zum Ekel gelesen werden. Ekel wird als für die Subjektwerdung in der frühen Kindheit notwendiges, gelerntes Verhaltensmuster beschrieben. Dieses wird zu einem Gefühl und im Verlauf der Persönlichkeitsentwicklung durch den Einfluss von Moral und Ästhetik weiter geprägt. Andererseits wird gezeigt, dass Analogien zwischen durch den Ekel ausgeschlossenen Triebregungen und Reaktionen auf Objekte der Lebensumwelt bestehen. '...

  19. Nur ein Test? – Auswirkungen nicht unterstützenden Testleiterverhaltens bei Intelligenztestungen auf den Selbstwert

    OpenAIRE

    Otterpohl, Nantje; Schwinger, Malte

    2015-01-01

    Intelligenztestungen gehören zum beruflichen Alltag in der psychologischen und sonderpädagogischen Praxis. Während verschiedene Studien darauf hinweisen, dass bei der Durchführung von Intelligenztests die Art der Testinstruktion sowie das Testleiterverhalten einen bedeutsamen Einfluss auf die Testangst und die Testleistung haben, wurde bisher kaum untersucht, inwiefern diese Faktoren auch einen Einfluss auf das Selbstwertgefühl nach der Testung haben. Zur Untersuchung dieser Frage wurden mit ...

  20. Schlafentzug: Wirkung auf Stimmung, Müdigkeit und spontane Schlafepisoden bei depressiven Patienten und gesunden Versuchspersonen

    OpenAIRE

    Hudjetz, Saskia

    2012-01-01

    Die Studie untersuchte 36 stationär behandelte Depressive und 24 gesunde Probanden zum Therapieeffekt eines 40-stündigen Schlafentzugs. Kontinuierlich wurde das Schlaf-EEG mit einem portablen System untersucht. Alle drei Stunden schätzten sie ihre Stimmung und Befindlichkeit auf visuellen Analogskalen ein. Die Ergebnisse bestätigen: Das Ansprechen auf Schlafentzug ist umso besser, je konsequenter Schlaf vermieden wird. Zwischen Depressiven und Gesunden zeigen sich gegenläufige Effekte hinsich...

  1. Die Arbeit der Organisationseinheit "Beteiligungsmanagement" im Gesamtkontext der Steuerung öffentlicher Unternehmen auf kommunaler Ebene

    OpenAIRE

    Creusen, Leander

    2014-01-01

    Diese Arbeit beschäftigt sich mit dem Thema Beteiligungsmanagement und der damit verbundenen Steuerung öffentlicher Unternehmen auf kommunaler Ebene. Der Ausgangspunkt der Untersuchung ist die Erkenntnis, dass eine Kommune keine absolute Kontrolle über ihre öffentlichen Unternehmen ausüben kann und sollte. Stattdessen wird angenommen, dass im Zuge einer effizienten Steuerung eine Fokussierung auf relevante Themen, Bereiche und Aktivitäten der öffentlichen Unternehmen erfolgt. Da die Steuerung...

  2. In vitro Endothelialisierung und Thrombozytenadhäsion auf titanbeschichteten polyether- und polykarbonat-basierten Polyurethanen

    OpenAIRE

    Li, Jing

    2016-01-01

    Die Titanbeschichtung von PUs unter Anwendung der PACVD-Technik ist eine angemessene Methode zur Verbesserung der Endothelialisierbarkeit dieser Polymere. Die Endothelzellen vermehren nur auf PEU, nicht auf untersuchte PCU. die Hämokompatibilität und die Elastizität des Materials ist nicht inkonsistent, um es klinisch als Gefäßprothese oder Herzunterstützungssystem nutzen zu können, muss erst noch im Chandler-Loop-Modell oder im Tiermodell untersucht werden.

  3. Photoschaltbare Azobenzol-modifizierte selbstorganisierte Monoschichten auf Gold(111)-Oberflächen

    OpenAIRE

    Bretthauer, Frauke

    2007-01-01

    Für die Entwicklung photoschaltbarer selbstorganisierter Monoschichten (SAMs) auf Gold(111)-Oberflächen wurden neue Azobenzol-terminierte Asparagussäure - und Liponsäurederivate synthetisiert. Um den Einfluss lateraler Wasserstoffbrückenbindungen auf Qualität und Orientierungsordnung der Schichten zu untersuchen, wurden Monolagen, die durch amid- und esterverknüpfte Verbindungen gebildet wurden, miteinander verglichen. Die Filmbildung aus der Lösung wurde in situ durch optische Frequenzverdop...

  4. Gefahrenfall und Entempirisierung. Anmerkungen zur Unterscheidung literarischer Akteure und Personen mit Bezug auf Oliver Jahraus’ Replik

    Directory of Open Access Journals (Sweden)

    David-Christopher Assmann

    2013-11-01

    Full Text Available Anmerkungen zur Unterscheidung literarischer Akteure und Personen mit Bezug auf Oliver Jahraus’ Replik. Die Replik setzt die seit der ersten Ausgabe von Textpraxis geführte Diskussion um eine Neufokussierung der systemtheoretischen Literaturwissenschaft fort. David-Christopher Assmann antwortet auf Oliver Jahraus’ Kritik an der Unterscheidung von Akteuren und Personen im Literatursystem, die jener in Ausgabe #3 in die Debatte eingeführt hat.

  5. Modellstudien zur Untersuchung des Einflusses solarer Prozesse auf die mittlere Atmosphäre

    OpenAIRE

    Nieder, Holger

    2015-01-01

    Ziel dieser Arbeit ist es, einen Beitrag zur Untersuchung des Einflusses der solaren Variabilität auf die Atmosphäre zu leisten. Übergeordnete Fragestellung ist der Einfluss solarer Variabilität auf Ozon, da Ozon aufgrund der Absorption von Strahlung von großer Bedeutung für das thermische Gleichgewicht und damit auch für die Dynamik der Atmosphäre ist.

  6. Influence of combustion air guidance on solid matter burnout and on pollutant emissions in grid incinerators; Einfluss der Verbrennungsluftfuehrung auf den Feststoffabbrand und auf das Schadstoffverhalten bei der Hausmuellverbrennung auf dem Rost

    Energy Technology Data Exchange (ETDEWEB)

    Hunsinger, H.; Seifert, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Technische Chemie

    2003-07-01

    The contribution investigates the influence of combustion air guidance strategies on process optimisation. In particular, it is investigated if efficient burnout correlates with low pollutant emissions and if the effects are similar or contrary for the different process goals. (orig.) [German] Der Einfluss von Brennstoffqualitaeten, der Ofengeometrie sowie von Feuerungsbetriebsparametern auf die Bildungsraten von Schadstoffen wie PCDD/F und NO{sub x} und auf die Transferraten von Schwermetallen, Chlor- und Schwefelverbindungen aus dem Brennstoffbett ins Rauchgas ist zur Zeit nur ungenuegend bekannt. Besonders die Frage, wie die primaere Forderung nach moeglichst vollstaendigem Ausbrand von Rauchgas und Rostasche mit weiteren Zielen wie niedrige Bildungsraten von Schadstoffen und Inertisierung der Rostasche korreliert, zeigt den Bedarf umfassender systematischer Untersuchungen auf. Im Rahmen dieses Beitrags soll als Beispiel fuer Modifikationen des Verbrennungsprozesses der Einfluss unterschiedlicher Verbrennungsluftfuehrungen auf die aufgefuehrten Optimierungsziele vorgestellt werden. Insbesondere soll der Frage nachgegangen werden, ob ein effizienter Ausbrand mit niedrigen Schadstoffbildungsraten korreliert und ob zwischen den Zielgroessen gleiche oder kontraere Wirkungen auftreten. (orig.)

  7. EXPLORER: Changing the molecular imaging paradigm with total-body PET/CT (Conference Presentation)

    Science.gov (United States)

    Cherry, Simon R.; Badawi, Ramsey D.; Jones, Terry

    2016-04-01

    Positron emission tomography (PET) is the highest sensitivity technique for human whole-body imaging studies. However, current clinical PET scanners do not make full use of the available signal, as they only permit imaging of a 15-25 cm segment of the body at one time. Given the limited sensitive region, whole-body imaging with clinical PET scanners requires relatively long scan times and subjects the patient to higher than necessary radiation doses. The EXPLORER initiative aims to build a 2-meter axial length PET scanner to allow imaging the entire subject at once, capturing nearly the entire available PET signal. EXPLORER will acquire data with ~40-fold greater sensitivity leading to a six-fold increase in reconstructed signal-to-noise ratio for imaging the total body. Alternatively, total-body images with the EXPLORER scanner will be able to be acquired in ~30 seconds or with ~0.15 mSv injected dose, while maintaining current PET image quality. The superior sensitivity will open many new avenues for biomedical research. Specifically for cancer applications, high sensitivity PET will enable detection of smaller lesions. Additionally, greater sensitivity will allow imaging out to 10 half-lives of positron emitting radiotracers. This will enable 1) metabolic ultra-staging with FDG by extending the uptake and clearance time to 3-5 hours to significantly improve contrast and 2) improved kinetic imaging with short-lived radioisotopes such as C-11, crucial for drug development studies. Frequent imaging studies of the same subject to study disease progression or to track response to therapy will be possible with the low dose capabilities of the EXPLORER scanner. The low dose capabilities will also open up new imaging possibilities in pediatrics and adolescents to better study developmental disorders. This talk will review the basis for developing total-body PET, potential applications, and review progress to date in developing EXPLORER, the first total-body PET scanner.

  8. Hybrid plasmonic magnetic nanoparticles as molecular specific agents for MRI/optical imaging and photothermal therapy of cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Timothy A [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States); Bankson, James [Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Aaron, Jesse [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States); Sokolov, Konstantin [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States)

    2007-08-15

    Nanoparticles which consist of a plasmonic layer and an iron oxide moiety could provide a promising platform for development of multimodal imaging and therapy approaches in future medicine. However, the feasibility of this platform has yet to be fully explored. In this study we demonstrated the use of gold-coated iron oxide hybrid nanoparticles for combined molecular specific MRI/optical imaging and photothermal therapy of cancer cells. The gold layer exhibits a surface plasmon resonance that provides optical contrast due to light scattering in the visible region and also presents a convenient surface for conjugating targeting moieties, while the iron oxide cores give strong T{sub 2} (spin-spin relaxation time) contrast. The strong optical absorption of the plasmonic gold layer also makes these nanoparticles a promising agent for photothermal therapy. We synthesized hybrid nanoparticles which specifically target epidermal growth factor receptor (EGFR), a common biomarker for many epithelial cancers. We demonstrated molecular specific MRI and optical imaging in MDA-MB-468 breast cancer cells. Furthermore, we showed that receptor-mediated aggregation of anti-EGFR hybrid nanoparticles allows selective destruction of highly proliferative cancer cells using a nanosecond pulsed laser at 700 nm wavelength, a significant shift from the peak absorbance of isolated hybrid nanoparticles at 532 nm.

  9. Hybrid plasmonic magnetic nanoparticles as molecular specific agents for MRI/optical imaging and photothermal therapy of cancer cells

    International Nuclear Information System (INIS)

    Nanoparticles which consist of a plasmonic layer and an iron oxide moiety could provide a promising platform for development of multimodal imaging and therapy approaches in future medicine. However, the feasibility of this platform has yet to be fully explored. In this study we demonstrated the use of gold-coated iron oxide hybrid nanoparticles for combined molecular specific MRI/optical imaging and photothermal therapy of cancer cells. The gold layer exhibits a surface plasmon resonance that provides optical contrast due to light scattering in the visible region and also presents a convenient surface for conjugating targeting moieties, while the iron oxide cores give strong T2 (spin-spin relaxation time) contrast. The strong optical absorption of the plasmonic gold layer also makes these nanoparticles a promising agent for photothermal therapy. We synthesized hybrid nanoparticles which specifically target epidermal growth factor receptor (EGFR), a common biomarker for many epithelial cancers. We demonstrated molecular specific MRI and optical imaging in MDA-MB-468 breast cancer cells. Furthermore, we showed that receptor-mediated aggregation of anti-EGFR hybrid nanoparticles allows selective destruction of highly proliferative cancer cells using a nanosecond pulsed laser at 700 nm wavelength, a significant shift from the peak absorbance of isolated hybrid nanoparticles at 532 nm

  10. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  11. Secondary Ion Mass Spectrometry Imaging of Molecular Distributions in Cultured Neurons and Their Processes: Comparative Analysis of Sample Preparation

    Science.gov (United States)

    Tucker, Kevin R.; Li, Zhen; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-11-01

    Neurons often exhibit a complex chemical distribution and topography; therefore, sample preparation protocols that preserve structures ranging from relatively large cell somata to small neurites and growth cones are important factors in secondary ion mass spectrometry (SIMS) imaging studies. Here, SIMS was used to investigate the subcellular localization of lipids and lipophilic species in neurons from Aplysia californica. Using individual neurons cultured on silicon wafers, we compared and optimized several SIMS sampling approaches. After an initial step to remove the high salt culturing media, formaldehyde, paraformaldehyde, and glycerol, and various combinations thereof, were tested for their ability to achieve cell stabilization during and after the removal of extracellular media. These treatments improved the preservation of cellular morphology as visualized with SIMS imaging. For analytes >250 Da, coating the cell surface with a 3.2 nm-thick gold layer increased the ion intensity; multiple analytes previously not observed or observed at low abundance were detected, including intact cholesterol and vitamin E molecular ions. However, once a sample was coated, many of the lower molecular mass (cultured neurons over a broad mass range with enhanced image contrast.

  12. Gone with the heat: a fundamental constraint on the imaging of dust and molecular gas in the early Universe.

    Science.gov (United States)

    Zhang, Zhi-Yu; Papadopoulos, Padelis P; Ivison, R J; Galametz, Maud; Smith, M W L; Xilouris, Emmanuel M

    2016-06-01

    Images of dust continuum and carbon monoxide (CO) line emission are powerful tools for deducing structural characteristics of galaxies, such as disc sizes, H2 gas velocity fields and enclosed H2 and dynamical masses. We report on a fundamental constraint set by the cosmic microwave background (CMB) on the observed structural and dynamical characteristics of galaxies, as deduced from dust continuum and CO-line imaging at high redshifts. As the CMB temperature rises in the distant Universe, the ensuing thermal equilibrium between the CMB and the cold dust and H2 gas progressively erases all spatial and spectral contrasts between their brightness distributions and the CMB. For high-redshift galaxies, this strongly biases the recoverable H2 gas and dust mass distributions, scale lengths, gas velocity fields and dynamical mass estimates. This limitation is unique to millimetre/submillimetre wavelengths and unlike its known effect on the global dust continuum and molecular line emission of galaxies, it cannot be addressed simply. We nevertheless identify a unique signature of CMB-affected continuum brightness distributions, namely an increasing rather than diminishing contrast between such brightness distributions and the CMB when the cold dust in distant galaxies is imaged at frequencies beyond the Raleigh-Jeans limit. For the molecular gas tracers, the same effect makes the atomic carbon lines maintain a larger contrast than the CO lines against the CMB.

  13. Development and Evaluation of an Open-Source Software Package “CGITA” for Quantifying Tumor Heterogeneity with Molecular Images

    Directory of Open Access Journals (Sweden)

    Yu-Hua Dean Fang

    2014-01-01

    Full Text Available Background. The quantification of tumor heterogeneity with molecular images, by analyzing the local or global variation in the spatial arrangements of pixel intensity with texture analysis, possesses a great clinical potential for treatment planning and prognosis. To address the lack of available software for computing the tumor heterogeneity on the public domain, we develop a software package, namely, Chang-Gung Image Texture Analysis (CGITA toolbox, and provide it to the research community as a free, open-source project. Methods. With a user-friendly graphical interface, CGITA provides users with an easy way to compute more than seventy heterogeneity indices. To test and demonstrate the usefulness of CGITA, we used a small cohort of eighteen locally advanced oral cavity (ORC cancer patients treated with definitive radiotherapies. Results. In our case study of ORC data, we found that more than ten of the current implemented heterogeneity indices outperformed SUVmean for outcome prediction in the ROC analysis with a higher area under curve (AUC. Heterogeneity indices provide a better area under the curve up to 0.9 than the SUVmean and TLG (0.6 and 0.52, resp.. Conclusions. CGITA is a free and open-source software package to quantify tumor heterogeneity from molecular images. CGITA is available for free for academic use at http://code.google.com/p/cgita.

  14. In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met

    Directory of Open Access Journals (Sweden)

    Sharon Moshitch-Moshkovitz

    2006-05-01

    Full Text Available The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor/scatter factor (HGF/SF, play an important role in normal developmental processes, as well as in tumorigenicity and metastasis. We constructed a green fluorescent protein (GFP Met chimeric molecule that functions similarly to the wild-type Met receptor and generated GFP-Met transgenic mice. These mice ubiquitously expressed GFP-Met in specific epithelial and endothelial cells and displayed enhanced GFP-Met fluorescence in sebaceous glands. Thirty-two percent of males spontaneously developed adenomas, adenocarcinomas, and angiosarcomas in their lower abdominal sebaceous glands. Approximately 70% of adenocarcinoma tumors metastasized to the kidneys, lungs, or liver. Quantitative subcellularresolution intravital imaging revealed very high levels of GFP-Met in tumor lesions and in single isolated cells surrounding them, relative to normal sebaceous glands. These single cells preceded the formation of local and distal metastases. Higher GFP-Met levels correlated with earlier tumor onset and aggressiveness, further demonstrating the role of Met-HGF/SF signaling in cellular transformation and acquisition of invasive and metastatic phenotypes. Our novel mouse model and high-resolution intravital molecular imaging create a powerful tool that enables direct realtime molecular imaging of receptor expression and localization during primary events of tumorigenicity and metastasis at single-cell resolution.

  15. Molekularbiologische Analyse von Her2/neu-Nanostrukturen in unterschiedlichen Brustkrebszelllinien auf Gen- und Proteinebene basierend auf hochaufgelösten fluoreszenzmikroskopischen Darstellungen

    OpenAIRE

    Müller, Patrick

    2011-01-01

    Untersuchungen zur Her2/neu-Amplifikation und -Expression, die im Zusammenhang mit der Entstehung von Brustkrebs und seiner Diagnostik stehen, sind für eine zusätzliche Verfeinerung der Diagnoseparameter und damit einer Verbesserung der Therapieansätze von enormer Bedeutung. In dieser Arbeit wurden durch hochauflösende lichtmikroskopische Verfahren grundlegende Untersuchungen zu Her2/neu sowohl auf Gen-, als auch auf Proteinebene durchgeführt, um neue und unterstützende Ansätze für einen bess...

  16. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

    International Nuclear Information System (INIS)

    To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications

  17. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao; Li, Ke [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China); Xu, Liang [The University of Kansas, Department of Molecular Biosciences (United States); Wu, Daocheng, E-mail: wudaocheng@mail.xjtu.edu.cn [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China)

    2014-12-15

    To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications.

  18. Synthesis and Bioconjugation of Gold Nanoparticles as Potential Molecular Probes for Light-Based Imaging Techniques

    NARCIS (Netherlands)

    Rayavarapu, Raja Gopal; Petersen, Wilma; Ungureanu, Constantin; Post, Janine N.; Leeuwen, van Ton G.; Manohar, Srirang

    2007-01-01

    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 techniqu

  19. Neuroendocrine tumours of the head and neck: anatomical, functional and molecular imaging and contemporary management

    Science.gov (United States)

    Subedi, Navaraj; Prestwich, Robin; Chowdhury, Fahmid; Patel, Chirag

    2013-01-01

    Abstract Neuroendocrine tumours (NETs) of the head and neck are rare neoplasms and can be of epithelial or non-epithelial differentiation. Although the natural history of NETs is variable, it is crucial to establish an early diagnosis of these tumours as they can be potentially curable. Conventional anatomical imaging and functional imaging using radionuclide scintigraphy and positron emission tomography/computed tomography can be complementary for the diagnosis, staging and monitoring of treatment response. This article describes and illustrates the imaging features of head and neck NETs, discusses the potential future role of novel positron-emitting tracers that are emerging into clinical practice and reviews contemporary management of these tumours. Familiarity with the choice of imaging techniques and the variety of imaging patterns and treatment options should help guide radiologists in the management of this rare but important subgroup of head and neck neoplasms. PMID:24240099

  20. One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular brain imaging

    International Nuclear Information System (INIS)

    Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes. (orig.)