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Sample records for integrated molecular imaging

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

    PubMed

    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

  2. Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging

    PubMed Central

    Constantinides, Christakis; Murphy, Kathy

    2016-01-01

    To-this-date, the exact molecular, cellular, and integrative physiological mechanisms of anesthesia remain largely unknown. Published evidence indicates that anesthetic effects are multifocal and occur in a time-dependent and coordinated manner, mediated via central, local, and peripheral pathways. Their effects can be modulated by a range of variables, and their elicited end-effect on the integrative physiological response is highly variable. This review summarizes the major cellular and molecular sites of anesthetic action with a focus on the paradigm of isoflurane (ISO) – the most commonly used anesthetic nowadays – and its use in prolonged in vivo rodent studies using imaging modalities, such as magnetic resonance imaging (MRI). It also presents established evidence for normal ranges of global and regional physiological cardiac function under ISO, proposes optimal, practical methodologies relevant to the use of anesthetic protocols for MRI and outlines the beneficial effects of nitrous oxide supplementation. PMID:27525256

  3. Performance evaluation of integrating detectors for near-infrared fluorescence molecular imaging

    NASA Astrophysics Data System (ADS)

    Zhu, Banghe; Rasmussen, John C.; Sevick-Muraca, Eva M.

    2014-05-01

    Although there has been a plethora of devices advanced for clinical translation, there has been no standards to compare and determine the optical device for fluorescence molecular imaging. In this work, we compare different CCD configurations using a solid phantom developed to mimic pM - fM concentrations of near-infrared fluorescent dyes in tissues. Our results show that intensified CCD systems (ICCDs) offer greater contrast at larger signal-tonoise ratios (SNRs) in comparison to their un-intensified CCD systems operated at clinically reasonable, sub-second acquisition times. Furthermore, we compared our investigational ICCD device to the commercial NOVADAQ SPY system, demonstrating different performance in both SNR and contrast.

  4. Applications of Molecular Imaging

    PubMed Central

    Galbán, Craig; Galbán, Stefanie; Van Dort, Marcian; Luker, Gary D.; Bhojani, Mahaveer S.; Rehemtualla, Alnawaz; Ross, Brian D.

    2015-01-01

    Today molecular imaging technologies play a central role in clinical oncology. The use of imaging techniques in early cancer detection, treatment response and new therapy development is steadily growing and has already significantly impacted clinical management of cancer. In this chapter we will overview three different molecular imaging technologies used for the understanding of disease biomarkers, drug development, or monitoring therapeutic outcome. They are (1) optical imaging (bioluminescence and fluorescence imaging) (2) magnetic resonance imaging (MRI), and (3) nuclear imaging (e.g, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). We will review the use of molecular reporters of biological processes (e.g. apoptosis and protein kinase activity) for high throughput drug screening and new cancer therapies, diffusion MRI as a biomarker for early treatment response and PET and SPECT radioligands in oncology. PMID:21075334

  5. EDITORIAL: Molecular Imaging Technology

    NASA Astrophysics Data System (ADS)

    Asai, Keisuke; Okamoto, Koji

    2006-06-01

    'Molecular Imaging Technology' focuses on image-based techniques using nanoscale molecules as sensor probes to measure spatial variations of various species (molecular oxygen, singlet oxygen, carbon dioxide, nitric monoxide, etc) and physical properties (pressure, temperature, skin friction, velocity, mechanical stress, etc). This special feature, starting on page 1237, contains selected papers from The International Workshop on Molecular Imaging for Interdisciplinary Research, sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, which was held at the Sendai Mediatheque, Sendai, Japan, on 8 9 November 2004. The workshop was held as a sequel to the MOSAIC International Workshop that was held in Tokyo in 2003, to summarize the outcome of the 'MOSAIC Project', a five-year interdisciplinary project supported by Techno-Infrastructure Program, the Special Coordination Fund for Promotion of Science Technology to develop molecular sensor technology for aero-thermodynamic research. The workshop focused on molecular imaging technology and its applications to interdisciplinary research areas. More than 110 people attended this workshop from various research fields such as aerospace engineering, automotive engineering, radiotechnology, fluid dynamics, bio-science/engineering and medical engineering. The purpose of this workshop is to stimulate intermixing of these interdisciplinary fields for further development of molecular sensor and imaging technology. It is our pleasure to publish the seven papers selected from our workshop as a special feature in Measurement and Science Technology. We will be happy if this issue inspires people to explore the future direction of molecular imaging technology for interdisciplinary research.

  6. Integrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation.

    PubMed

    Boxman, Jonathan; Sagy, Naor; Achanta, Sirisha; Vadigepalli, Rajanikanth; Nachman, Iftach

    2016-01-01

    Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a 'developmental clock' using the Brachyury-GFP signal onset timing. Mapping snapshot gene expression measurements to this clock revealed their temporal trends, indicating that loss of pluripotency, formation of primitive streak and mesodermal lineage progression are synchronized in EBs. Exogenous activation of Wnt or BMP signaling accelerated the intrinsic clock. CHIR down-regulated Wnt3, allowing insights into dependency mechanisms between canonical Wnt signaling and multiple genes. Our findings reveal a developmental clock characteristic of an early differentiation program common to all EBs, further establishing them as an in vitro developmental model. PMID:27530599

  7. Integrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation

    PubMed Central

    Boxman, Jonathan; Sagy, Naor; Achanta, Sirisha; Vadigepalli, Rajanikanth; Nachman, Iftach

    2016-01-01

    Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a ‘developmental clock’ using the Brachyury-GFP signal onset timing. Mapping snapshot gene expression measurements to this clock revealed their temporal trends, indicating that loss of pluripotency, formation of primitive streak and mesodermal lineage progression are synchronized in EBs. Exogenous activation of Wnt or BMP signaling accelerated the intrinsic clock. CHIR down-regulated Wnt3, allowing insights into dependency mechanisms between canonical Wnt signaling and multiple genes. Our findings reveal a developmental clock characteristic of an early differentiation program common to all EBs, further establishing them as an in vitro developmental model. PMID:27530599

  8. Photoacoustic molecular imaging

    NASA Astrophysics Data System (ADS)

    Kiser, William L., Jr.; Reinecke, Daniel; DeGrado, Timothy; Bhattacharyya, Sibaprasad; Kruger, Robert A.

    2007-02-01

    It is well documented that photoacoustic imaging has the capability to differentiate tissue based on the spectral characteristics of tissue in the optical regime. The imaging depth in tissue exceeds standard optical imaging techniques, and systems can be designed to achieve excellent spatial resolution. A natural extension of imaging the intrinsic optical contrast of tissue is to demonstrate the ability of photoacoustic imaging to detect contrast agents based on optically absorbing dyes that exhibit well defined absorption peaks in the infrared. The ultimate goal of this project is to implement molecular imaging, in which Herceptin TM, a monoclonal antibody that is used as a therapeutic agent in breast cancer patients that over express the HER2 gene, is labeled with an IR absorbing dye, and the resulting in vivo bio-distribution is mapped using multi-spectral, infrared stimulation and subsequent photoacoustic detection. To lay the groundwork for this goal and establish system sensitivity, images were collected in tissue mimicking phantoms to determine maximum detection depth and minimum detectable concentration of Indocyanine Green (ICG), a common IR absorbing dye, for a single angle photoacoustic acquisition. A breast mimicking phantom was constructed and spectra were also collected for hemoglobin and methanol. An imaging schema was developed that made it possible to separate the ICG from the other tissue mimicking components in a multiple component phantom. We present the results of these experiments and define the path forward for the detection of dye labeled Herceptin TM in cell cultures and mice models.

  9. Molecular Imaging in Genetic Medicine

    PubMed Central

    Jacob, Ayden; Van Gestel, Frederick; Yaghoubi, Shahriar

    2016-01-01

    The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine.  PMID:27186447

  10. Molecular imaging in atherosclerosis

    PubMed Central

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

    2010-01-01

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

  11. Molecular probes for cardiovascular imaging.

    PubMed

    Liang, Grace; Nguyen, Patricia K

    2016-08-01

    Molecular probes provide imaging signal and contrast for the visualization, characterization, and measurement of biological processes at the molecular level. These probes can be designed to target the cell or tissue of interest and must be retained at the imaging site until they can be detected by the appropriate imaging modality. In this article, we will discuss the basic design of molecular probes, differences among the various types of probes, and general strategies for their evaluation of cardiovascular disease. PMID:27189171

  12. Time-resolved molecular imaging

    NASA Astrophysics Data System (ADS)

    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.

  13. Molecular imaging in ovarian cancer.

    PubMed

    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

  14. Integration methods for molecular dynamics

    SciTech Connect

    Leimkuhler, B.J.; Reich, S.; Skeel, R.D.

    1996-12-31

    Classical molecular dynamics simulation of a macromolecule requires the use of an efficient time-stepping scheme that can faithfully approximate the dynamics over many thousands of timesteps. Because these problems are highly nonlinear, accurate approximation of a particular solution trajectory on meaningful time intervals is neither obtainable nor desired, but some restrictions, such as symplecticness, can be imposed on the discretization which tend to imply good long term behavior. The presence of a variety of types and strengths of interatom potentials in standard molecular models places severe restrictions on the timestep for numerical integration used in explicit integration schemes, so much recent research has concentrated on the search for alternatives that possess (1) proper dynamical properties, and (2) a relative insensitivity to the fastest components of the dynamics. We survey several recent approaches. 48 refs., 2 figs.

  15. Molecular SPECT Imaging: An Overview

    PubMed Central

    Khalil, Magdy M.; Tremoleda, Jordi L.; Bayomy, Tamer B.; Gsell, Willy

    2011-01-01

    Molecular imaging has witnessed a tremendous change over the last decade. Growing interest and emphasis are placed on this specialized technology represented by developing new scanners, pharmaceutical drugs, diagnostic agents, new therapeutic regimens, and ultimately, significant improvement of patient health care. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. Moreover, the last section covers several application, of μSPECT imaging in many areas of disease detection and diagnosis. PMID:21603240

  16. Targeted molecular imaging in oncology.

    PubMed

    Yang, David J; Kim, E Edmund; Inoue, Tomio

    2006-01-01

    Improvement of scintigraphic tumor imaging is extensively determined by the development of more tumor specific radiopharmaceuticals. Thus, to improve the differential diagnosis, prognosis, planning and monitoring of cancer treatment, several functional pharmaceuticals have been developed. Application of molecular targets for cancer imaging, therapy and prevention using generator-produced isotopes is the major focus of ongoing research projects. Radionuclide imaging modalities (positron emission tomography, PET; single photon emission computed tomography, SPECT) are diagnostic cross-sectional imaging techniques that map the location and concentration of radionuclide-labeled radiotracers. 99mTc- and 68Ga-labeled agents using ethylenedicysteine (EC) as a chelator were synthesized and their potential uses to assess tumor targets were evaluated. 99mTc (t1/2 = 6 hr, 140 keV) is used for SPECT and 68Ga (t1/2 = 68 min, 511 keV) for PET. Molecular targets labeled with Tc-99m and Ga-68 can be utilized for prediction of therapeutic response, monitoring tumor response to treatment and differential diagnosis. Molecular targets for oncological research in (1) cell apoptosis, (2) gene and nucleic acid-based approach, (3) angiogenesis (4) tumor hypoxia, and (5) metabolic imaging are discussed. Numerous imaging ligands in these categories have been developed and evaluated in animals and humans. Molecular targets were imaged and their potential to redirect optimal cancer diagnosis and therapeutics were demonstrated. PMID:16485568

  17. Design and Development of Molecular Imaging Probes

    PubMed Central

    Chen, Kai; Chen, Xiaoyuan

    2013-01-01

    Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living subjects, has rapidly gained importance in the dawning era of personalized medicine. Molecular imaging takes advantage of the traditional diagnostic imaging techniques and introduces molecular imaging probes to determine the expression of indicative molecular markers at different stages of diseases and disorders. As a key component of molecular imaging, molecular imaging probe must be able to specifically reach the target of interest in vivo while retaining long enough to be detected. A desirable molecular imaging probe with clinical translation potential is expected to have unique characteristics. Therefore, design and development of molecular imaging probe is frequently a challenging endeavor for medicinal chemists. This review summarizes the general principles of molecular imaging probe design and some fundamental strategies of molecular imaging probe development with a number of illustrative examples. PMID:20388106

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

    PubMed Central

    Chen, Zhi-Yi; Wang, Yi-Xiang; Lin, Yan; Zhang, Jin-Shan; Yang, Feng; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    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. PMID:24689058

  19. [Molecular imaging in neurological diseases].

    PubMed

    Reimold, M; la Fougère, C

    2016-07-01

    In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, (18)F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma. PMID:27306201

  20. Genome Clone Libraries and Data from the Integrated Molecular Analysis of Genomes and their Expression (I.M.A.G.E.) Consortium

    DOE Data Explorer

    The I.M.A.G.E. Consortium was initiated in 1993 by four academic groups on a collaborative basis after informal discussions led to a common vision of how to achieve an important goal in the study of the human genome: the Integrated Molecular Analysis of Genomes and their Expression Consortium's primary goal is to create arrayed cDNA libraries and associated bioinformatics tools, and make them publicly available to the research community. The primary organisms of interest include intensively studied mammalian species, including human, mouse, rat and non-human primate species. The Consortium has also focused on several commonly studied model organisms; as part of this effort it has arrayed cDNAs from zebrafish, and Fugu (pufferfish) as well as Xenopus laevis and X. tropicalis (frog). Utilizing high speed robotics, over nine million individual cDNA clones have been arrayed into 384-well microtiter plates, and sufficient replicas have been created to distribute copies both to sequencing centers and to a network of five distributors located worldwide. The I.M.A.G.E. Consortium represents the world's largest public cDNA collection, and works closely with the National Institutes of Health's Mammalian Gene Collection(MGC) to help it achieve its goal of creating a full-length cDNA clone for every human and mouse gene. I.M.A.G.E. is also a member of the ORFeome Collaboration, working to generate a complete set of expression-ready open reading frame clones representing each human gene. Custom informatics tools have been developed in support of these projects to better allow the research community to select clones of interest and track and collect all data deposited into public databases about those clones and their related sequences. I.M.A.G.E. clones are publicly available, free of any royalties, and may be used by anyone agreeing with the Consortium's guidelines.

  1. Optical molecular imaging in PDT

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya; Snyder, John W.; Foster, Thomas H.

    2007-02-01

    Motivated by recent successes in fluorescence imaging of whole mount tissue preparations and by rapid progress in the fields of molecular imaging and molecular biology, we are exploring a number of applications of optical fluorescence imaging in superficial murine tumor models in vivo. Imaging the PDT-induced expression of the heat shock protein 70 (HSP70) in cells and in vivo is accomplished using stably transfected EMT6 cells in which the gene for GFP is under the control of the HSP70 promoter. These cells readily form solid tumors in BALB/c mice, enabling the direct imaging of the extent and time course of the activation of this promoter, with each mouse serving as its own control. Imaging of similarly transfected EMT6 cells with a HIF-1α/GFP fusion protein vector enables visualization of HIF-1α translocation to the nucleus. Recently, we have accomplished fluorescent labeling of surface antigens in vivo using intratumor and intravenous injection of fluorophore-conjugated antibodies. Injection of deep-red fluorophore-conjugated-anti-CD31 enables confocal fluorescence imaging of the tumor vasculature to depths of at least 100 microns. With the vessels rendered fluorescent in this way, a number of interesting studies become possible in the living mouse, including the direct visualization of photosensitizer distribution from perfused vessels. Using the appropriate fluorophore-conjugated antibodies, we have also been able to image infiltrating granulocytes in EMT6 tumors in response to PDT in vivo.

  2. The evolving role of nuclear molecular imaging in cancer

    PubMed Central

    Kurdziel, KA; Ravizzini, G; Croft, BY; Tatum, JL; Choyke, PL; Kobayashi, H

    2008-01-01

    Background Novel therapies targeted to specific tumor pathways are entering the clinic. The need for in vivo monitoring of resulting molecular changes, particularly with respect to the tumor microenvironment, is growing. Molecular imaging is evolving to include a variety of imaging methods to enable in vivo monitoring of cellular and molecular processes. Objectives This article reviews the emerging role of molecular imaging in the development of improved therapeutic strategies that provide better patient selection for therapeutic personalization (i.e. determine which therapies have the greatest chance of success given the individual patient’s disease genetic, and phenotypical profile). Methods In order to illustrate the utility of integrating molecular imaging into therapy development strategies, current and emerging applications of nuclear molecular imaging strategies will be compared with conventional strategies. Proposed methods of integrating molecular imaging techniques into cancer therapeutic development and limitations of these techniques will be discussed. Results/Conclusion Molecular imaging provides a variety of new tools to accelerate the development of cancer therapies. The recent drive to develop molecular imaging probes and standardize molecular imaging techniques is creating the scaffolding for the evolving paradigm shift to personalized cancer therapy. PMID:19122861

  3. Molecular Imaging of Plaque Vulnerability

    PubMed Central

    Tavakoli, Sina; Vashist, Aseem; Sadeghi, Mehran M.

    2014-01-01

    Over the past decade significant progress has been made in the development of novel imaging strategies focusing on the biology of the vessel wall for identification of vulnerable plaques. While the majority of these studies are still in the preclinical stage, few techniques (e.g., 18F-FDG and 18F-NaF PET imaging) have already been evaluated in clinical studies with promising results. Here, we will briefly review the pathobiology of atherosclerosis and discuss molecular imaging strategies that have been developed to target these events, with an emphasis on mechanisms that are associated with atherosclerotic plaque vulnerability. PMID:25124827

  4. Molecular imaging in cervical cancer.

    PubMed

    Khan, Sairah R; Rockall, Andrea G; Barwick, Tara D

    2016-06-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID:26859085

  5. Imaging molecular orbitals using photoionization

    NASA Astrophysics Data System (ADS)

    Santra, Robin

    2006-10-01

    The interpretation of a recent experiment using high-order harmonic generation [Itatani et al., Nature 432 (2004) 867] as a measurement of the highest occupied molecular orbital of a molecule is conceptually problematic, even if the independent-particle picture is taken seriously. Guided by the relationship between the amplitude for one-photon-induced electron emission and the electron-ion recombination amplitude in the three-step model of high-order harmonic generation, it is argued that synchrotron-based photoionization might be a superior approach to imaging molecular orbitals. Within the Hartree-Fock independent-particle picture, the molecular-frame photoelectron angular distributions, measured as a function of photon energy, could be used to reconstruct all orbitals occupied in the Hartree-Fock ground state of the molecule investigated. It is suggested that laser alignment techniques could be employed to facilitate the measurement of the molecular-frame photoelectron angular distributions.

  6. Cancer Stratification by Molecular Imaging

    PubMed Central

    Weber, Justus; Haberkorn, Uwe; Mier, Walter

    2015-01-01

    The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2). Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter), as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers. PMID:25749472

  7. Molecular Imaging with Theranostic Nanoparticles

    PubMed Central

    Jokerst, Jesse V.; Gambhir, Sanjiv S.

    2011-01-01

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

  8. Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research

    PubMed Central

    2008-01-01

    learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA. PMID:18831773

  9. Molecular Imaging of Pituitary Pathology.

    PubMed

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID:27002335

  10. Advances in multimodality molecular imaging

    PubMed Central

    Zaidi, Habib; Prasad, Rameshwar

    2009-01-01

    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. PMID:20098557

  11. SYMPOSIUM ON MULTIMODALITY CARDIOVASCULAR MOLECULAR IMAGING IMAGING TECHNOLOGY - PART 2

    PubMed Central

    de Kemp, Robert A.; Epstein, Frederick H.; Catana, Ciprian; Tsui, Benjamin M.W.; Ritman, Erik L.

    2013-01-01

    Rationale The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components and tracing of solute transport mechanisms. With the increasing use of small animals for research such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Methods Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI and CT, are increasingly applicable due to recent advances in novel scanner hardware, image reconstruction software and availability of novel molecules which have enhanced sensitivity in these methodologies. Results Micro-PET has been advanced by development of detector arrays that provide higher resolution and positron emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity by increased magnet field strength and development of special purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes which can be directly related to the molecular information. This is further strengthened by the synergistic integration of the PET with MRI. Micro-SPECT has been improved by use of coded aperture imaging approaches as well as image reconstruction algorithms which can better deal with the photon limited scan data. The limited spatial resolution can be partially overcome by integrating the SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments of high spatial resolution photon counting and spectrally-sensitive imaging arrays, combined with x-ray optical devices, have promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially of bio

  12. Targeted Molecular Imaging in Oncology: Focus on Radiation Therapy

    PubMed Central

    Nimmagadda, Sridhar; Ford, Eric C.; Wong, John W.; Pomper, Martin G.

    2008-01-01

    Anatomically based technologies (CT, MR, etc.) are in routine use in radiotherapy for planning and assessment purposes. Even with improvements in imaging, however, radiotherapy is still limited in efficacy and toxicity in certain applications. Further advances may be provided by technologies that image the molecular activities of tumors and normal tissues. Possible uses for molecular imaging include better localization of tumor regions and early assay for the radiation response of tumors and normal tissues. Critical to the success of this approach is the identification and validation of molecular probes that are suitable in the radiotherapy context. Recent developments in molecular imaging probes and integration of functional imaging with radiotherapy are promising. This review focuses on recent advances in molecular imaging strategies and probes that may aid in improving the efficacy of radiotherapy. PMID:18314068

  13. Molecular Imaging of Neuroendocrine Tumors

    PubMed Central

    Carrasquillo, Jorge A.; Chen, Clara C.

    2014-01-01

    Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals. PMID:21167384

  14. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; Burger, Irene A; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. PMID:26587888

  15. Flightspeed Integral Image Analysis Toolkit

    NASA Technical Reports Server (NTRS)

    Thompson, David R.

    2009-01-01

    The Flightspeed Integral Image Analysis Toolkit (FIIAT) is a C library that provides image analysis functions in a single, portable package. It provides basic low-level filtering, texture analysis, and subwindow descriptor for applications dealing with image interpretation and object recognition. Designed with spaceflight in mind, it addresses: Ease of integration (minimal external dependencies) Fast, real-time operation using integer arithmetic where possible (useful for platforms lacking a dedicated floatingpoint processor) Written entirely in C (easily modified) Mostly static memory allocation 8-bit image data The basic goal of the FIIAT library is to compute meaningful numerical descriptors for images or rectangular image regions. These n-vectors can then be used directly for novelty detection or pattern recognition, or as a feature space for higher-level pattern recognition tasks. The library provides routines for leveraging training data to derive descriptors that are most useful for a specific data set. Its runtime algorithms exploit a structure known as the "integral image." This is a caching method that permits fast summation of values within rectangular regions of an image. This integral frame facilitates a wide range of fast image-processing functions. This toolkit has applicability to a wide range of autonomous image analysis tasks in the space-flight domain, including novelty detection, object and scene classification, target detection for autonomous instrument placement, and science analysis of geomorphology. It makes real-time texture and pattern recognition possible for platforms with severe computational restraints. The software provides an order of magnitude speed increase over alternative software libraries currently in use by the research community. FIIAT can commercially support intelligent video cameras used in intelligent surveillance. It is also useful for object recognition by robots or other autonomous vehicles

  16. Companion Diagnostics and Molecular Imaging.

    PubMed

    Puranik, Ameya D; Kulkarni, Harshad R; Baum, Richard P

    2015-01-01

    Companion diagnostics (CDx) is a positive attempt in the direction of improving the drug development process, especially in the field of oncology, with the advent of newer targeted therapies. It helps the oncologist in deciding the choice of treatment for the individual patient. The role of CDx assays has attracted the attention of regulators, and especially the US Food and Drug Administration developed regulatory strategies for CDx and the drug-diagnostic codevelopment project. For an increasing number of cancer patients, the treatment selection will depend on the result generated by a CDx assay, and consequently this type of assay has become critical for the care and safety of the patients. In addition to the assay-based approach, molecular imaging with its ability to image at the genetic and receptor level has made foray into the field of drug development and personalized medicine. We shall review these aspects of CDx, with special focus on molecular imaging and the upcoming concept of Theranostics. PMID:26049701

  17. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  18. Molecular imaging probe development: a chemistry perspective

    PubMed Central

    Nolting, Donald D; Nickels, Michael L; Guo, Ning; Pham, Wellington

    2012-01-01

    Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed. PMID:22943038

  19. Molecular Imaging: Current Status and Emerging Strategies

    PubMed Central

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

    2011-01-01

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

  20. Molecular Imaging with Single-Walled Carbon Nanotubes

    PubMed Central

    Hong, Hao; Gao, Ting; Cai, Weibo

    2011-01-01

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

  1. Recent advances in ophthalmic molecular imaging.

    PubMed

    Ramos de Carvalho, J Emanuel; Verbraak, Frank D; Aalders, Maurice C; van Noorden, Cornelis J; Schlingemann, Reinier O

    2014-01-01

    The aim of molecular imaging techniques is the visualization of molecular processes and functional changes in living animals and human patients before morphological changes occur at the cellular and tissue level. Ophthalmic molecular imaging is still in its infancy and has mainly been used in small animals for pre-clinical research. The goal of most of these pre-clinical studies is their translation into ophthalmic molecular imaging techniques in clinical care. We discuss various molecular imaging techniques and their applications in ophthalmology. PMID:24529711

  2. Molecular Imaging System for Monitoring Tumor Angiogenesis

    NASA Astrophysics Data System (ADS)

    Aytac, Esra; Burcin Unlu, Mehmet

    2012-02-01

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

  3. Label-free molecular imaging

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  4. Effects of high hydrostatic pressure on Escherichia coli ultrastructure, membrane integrity and molecular composition as assessed by FTIR spectroscopy and microscopic imaging techniques.

    PubMed

    Prieto-Calvo, María; Prieto, Miguel; López, Mercedes; Alvarez-Ordóñez, Avelino

    2014-01-01

    High hydrostatic pressure (HHP) is a novel food processing technology that is considered as an attractive alternative to conventional heat treatments for the preservation of foods, due to its lethal effects on pathogenic and spoilage microorganisms, while causing minor effects on food quality and sensorial attributes. This study is aimed at investigating how HHP treatments at varying intensities in the range 50-900 MPa affect the viability, membrane integrity, ultrastructure and molecular composition of Escherichia coli. Results of membrane integrity tests (measurement of cellular leakage and monitoring of propidium iodide uptake through fluorescence microscopy) and ultrastructural observations by transmission electron microscopy demonstrated that HHP gave rise to cellular enlargement, membrane damage or detachment, DNA and protein denaturation and loss of intracellular contents. Fourier-transform infrared (FTIR) spectroscopy analyses evidenced minor changes in molecular composition in response to high pressures, which were mostly observed on the spectral region w4 (1200-900 cm-1), mainly informative of carbohydrates and polysaccharides of the cell wall. These findings suggest that exposure of E. coli cells to HHP causes alterations in their physical integrity while producing minor modifications in biochemical cellular composition. The current study increases the knowledge on the mechanisms of E. coli inactivation by HHP and provides valuable information for the design of more effective food preservation regimes based on the integration of mild HHP in combination with other food preservation strategies into a multi-target hurdle technology approach. PMID:25529018

  5. Integrating IR detector imaging systems

    NASA Technical Reports Server (NTRS)

    Bailey, G. C. (Inventor)

    1984-01-01

    An integrating IR detector array for imaging is provided in a hybrid circuit with InSb mesa diodes in a linear array, a single J-FET preamplifier for readout, and a silicon integrated circuit multiplexer. Thin film conductors in a fan out pattern deposited on an Al2O3 substrate connect the diodes to the multiplexer, and thick film conductors also connect the reset switch and preamplifier to the multiplexer. Two phase clock pulses are applied with a logic return signal to the multiplexer through triax comprised of three thin film conductors deposited between layers. A lens focuses a scanned image onto the diode array for horizontal read out while a scanning mirror provides vertical scan.

  6. Molecular imaging promotes progress in orthopedic research.

    PubMed

    Mayer-Kuckuk, Philipp; Boskey, Adele L

    2006-11-01

    Modern orthopedic research is directed towards the understanding of molecular mechanisms that determine development, maintenance and health of musculoskeletal tissues. In recent years, many genetic and proteomic discoveries have been made which necessitate investigation under physiological conditions in intact, living tissues. Molecular imaging can meet this demand and is, in fact, the only strategy currently available for noninvasive, quantitative, real-time biology studies in living subjects. In this review, techniques of molecular imaging are summarized, and applications to bone and joint biology are presented. The imaging modality most frequently used in the past was optical imaging, particularly bioluminescence and near-infrared fluorescence imaging. Alternate technologies including nuclear and magnetic resonance imaging were also employed. Orthopedic researchers have applied molecular imaging to murine models including transgenic mice to monitor gene expression, protein degradation, cell migration and cell death. Within the bone compartment, osteoblasts and their stem cells have been investigated, and the organic and mineral bone phases have been assessed. These studies addressed malignancy and injury as well as repair, including fracture healing and cell/gene therapy for skeletal defects. In the joints, molecular imaging has focused on the inflammatory and tissue destructive processes that cause arthritis. As described in this review, the feasibility of applying molecular imaging to numerous areas of orthopedic research has been demonstrated and will likely result in an increase in research dedicated to this powerful strategy. Molecular imaging holds great promise in the future for preclinical orthopedic research as well as next-generation clinical musculoskeletal diagnostics. PMID:16843078

  7. Molecular Imaging of Pancreatic Cancer with Antibodies

    PubMed Central

    2015-01-01

    Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

  8. Molecular-Genetic Imaging of Cancer

    PubMed Central

    Minn, Il; Menezes, Mitchell E.; Sarkar, Siddik; Yarlagadda, Keerthi; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.; Pomper, Martin G.

    2015-01-01

    Molecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer. Combination with therapy, namely, generating molecular-genetic theranostic constructs, will provide further impetus for clinical translation of this promising technology. PMID:25287688

  9. Anatomical and molecular imaging of skin cancer

    PubMed Central

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼ 5%) and nonmelanoma (∼ 95%), which can be further categorized into basal cell carcinoma, squamous cell carcinoma, and some rare skin cancer types. Biopsy is still the gold standard for skin cancer evaluation in the clinic. Various anatomical imaging techniques have been used to evaluate different types of skin cancer lesions, including laser scanning confocal microscopy, optical coherence tomography, high-frequency ultrasound, terahertz pulsed imaging, magnetic resonance imaging, and some other recently developed techniques such as photoacoustic microscopy. However, anatomical imaging alone may not be sufficient in guiding skin cancer diagnosis and therapy. Over the last decade, various molecular imaging techniques (in particular single photon emission computed tomography and positron emission tomography) have been investigated for skin cancer imaging. The pathways or molecular targets that have been studied include glucose metabolism, integrin αvβ3, melanocortin-1 receptor, high molecular weight melanoma-associated antigen, and several other molecular markers. Preclinical molecular imaging is thriving all over the world, while clinical molecular imaging has not lived up to the expectations because of slow bench-to-bedside translation. It is likely that this situation will change in the near future and molecular imaging will truly play an important role in personalized medicine of melanoma patients. PMID:21437135

  10. Molecular magnetic resonance imaging in cancer.

    PubMed

    Haris, Mohammad; Yadav, Santosh K; Rizwan, Arshi; Singh, Anup; Wang, Ena; Hariharan, Hari; Reddy, Ravinder; Marincola, Francesco M

    2015-01-01

    The ability to identify key biomolecules and molecular changes associated with cancer malignancy and the capacity to monitor the therapeutic outcome against these targets is critically important for cancer treatment. Recent developments in molecular imaging based on magnetic resonance (MR) techniques have provided researchers and clinicians with new tools to improve most facets of cancer care. Molecular imaging is broadly described as imaging techniques used to detect molecular signature at the cellular and gene expression levels. This article reviews both established and emerging molecular MR techniques in oncology and discusses the potential of these techniques in improving the clinical cancer care. It also discusses how molecular MR, in conjunction with other structural and functional MR imaging techniques, paves the way for developing tailored treatment strategies to enhance cancer care. PMID:26394751

  11. Molecular imaging of oncolytic viral therapy

    PubMed Central

    Haddad, Dana; Fong, Yuman

    2015-01-01

    Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy. PMID:27119098

  12. Molecular imaging of oncolytic viral therapy.

    PubMed

    Haddad, Dana; Fong, Yuman

    2015-01-01

    Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy. PMID:27119098

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Activatable Molecular Probes for Cancer Imaging

    PubMed Central

    Lee, Seulki; Xie, Jin; Chen, Xiaoyuan

    2013-01-01

    The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging. PMID:20388112

  15. Fluorescence lifetime-based optical molecular imaging.

    PubMed

    Kumar, Anand T N

    2011-01-01

    Fluorescence lifetime is a powerful contrast mechanism for in vivo molecular imaging. In this chapter, we describe instrumentation and methods to optimally exploit lifetime contrast using a time domain fluorescence tomography system. The key features of the system are the use of point excitation in free-space using ultrashort laser pulses and non-contact detection using a gated, intensified CCD camera. The surface boundaries of the imaging volume are acquired using a photogrammetric camera integrated with the imaging system, and implemented in theoretical models of light propagation in biological tissue. The time domain data are optimally analyzed using a lifetime-based tomography approach, which is based on extracting a tomographic set of lifetimes and decay amplitudes from the long time decay portion of the time domain data. This approach improves the ability to locate in vivo targets with a resolution better than conventional optical methods. The application of time domain lifetime multiplexing and tomography are illustrated using phantoms and tumor bearing mouse model of breast adenocarcinoma. In the latter application, the time domain approach allows an improved detection of fluorescent protein signals from intact nude mice in the presence of background autofluorescence. This feature has potential applications for longitudinal pre-clinical evaluation of drug treatment response as well as to address fundamental questions related to tumor physiology and metastasis. PMID:21153381

  16. Optical Molecular Imaging in the Gastrointestinal Tract

    PubMed Central

    Carns, Jennifer; Keahey, Pelham; Quang, Timothy; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2013-01-01

    Recent developments in optical molecular imaging allow for real-time identification of morphological and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high resolution imaging modalities currently in pre-clinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. Finally, new approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated. PMID:23735112

  17. Molecular Imaging of Healing After Myocardial Infarction

    PubMed Central

    Naresh, Nivedita K; Ben-Mordechai, Tamar; Leor, Jonathan

    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. However, new imaging methods can be used to assess biological processes at the cellular and molecular level. We review molecular imaging techniques for evaluating the biology of infarct healing and repair. Specifically, we cover recent advances in imaging the various phases of MI and infarct healing such as apoptosis, inflammation, angiogenesis, extracellular matrix deposition, and scar formation. Significant progress has been made in preclinical molecular imaging, and future challenges include translation of these methods to clinical practice. PMID:21869911

  18. Molecular Imaging of Proteases in Cancer

    PubMed Central

    Yang, Yunan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2010-01-01

    Proteases play important roles during tumor angiogenesis, invasion, and metastasis. Various molecular imaging techniques have been employed for protease imaging: optical (both fluorescence and bioluminescence), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). In this review, we will summarize the current status of imaging proteases in cancer with these techniques. Optical imaging of proteases, in particular with fluorescence, is the most intensively validated and many of the imaging probes are already commercially available. It is generally agreed that the use of activatable probes is the most accurate and appropriate means for measuring protease activity. Molecular imaging of proteases with other techniques (i.e. MRI, SPECT, and PET) has not been well-documented in the literature which certainly deserves much future effort. Optical imaging and molecular MRI of protease activity has very limited potential for clinical investigation. PET/SPECT imaging is suitable for clinical investigation; however the optimal probes for PET/SPECT imaging of proteases in cancer have yet to be developed. Successful development of protease imaging probes with optimal in vivo stability, tumor targeting efficacy, and desirable pharmacokinetics for clinical translation will eventually improve cancer patient management. Not limited to cancer, these protease-targeted imaging probes will also have broad applications in other diseases such as arthritis, atherosclerosis, and myocardial infarction. PMID:20234801

  19. Molecular imaging of movement disorders

    PubMed Central

    Lizarraga, Karlo J; Gorgulho, Alessandra; Chen, Wei; De Salles, Antonio A

    2016-01-01

    caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders. PMID:27029029

  20. Molecular imaging of movement disorders.

    PubMed

    Lizarraga, Karlo J; Gorgulho, Alessandra; Chen, Wei; De Salles, Antonio A

    2016-03-28

    -to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders. PMID:27029029

  1. Molecular Imaging in Optical Coherence Tomography

    PubMed Central

    Mattison, Scott P.; Kim, Wihan; Park, Jesung; Applegate, Brian E.

    2015-01-01

    Optical coherence tomography (OCT) is a medical imaging technique that provides tomographic images at micron scales in three dimensions and high speeds. The addition of molecular contrast to the available morphological image holds great promise for extending OCT’s impact in clinical practice and beyond. Fundamental limitations prevent OCT from directly taking advantage of powerful molecular processes such as fluorescence emission and incoherent Raman scattering. A wide range of approaches is being researched to provide molecular contrast to OCT. Here we review those approaches with particular attention to those that derive their molecular contrast directly from modulation of the OCT signal. We also provide a brief overview of the multimodal approaches to gaining molecular contrast coincident with OCT. PMID:25821718

  2. Optical imaging: Ultrafast buffering by molecular gas

    NASA Astrophysics Data System (ADS)

    Hertz, Edouard; Lavorel, Bruno; Faucher, Olivier

    2011-02-01

    A simple molecular gas sample can be used to achieve ultrafast optical buffering in two-dimensional optical imaging, thus serving as a promising extension of the well-developed liquid-crystal display technology.

  3. Oncological image analysis: medical and molecular image analysis

    NASA Astrophysics Data System (ADS)

    Brady, Michael

    2007-03-01

    This paper summarises the work we have been doing on joint projects with GE Healthcare on colorectal and liver cancer, and with Siemens Molecular Imaging on dynamic PET. First, we recall the salient facts about cancer and oncological image analysis. Then we introduce some of the work that we have done on analysing clinical MRI images of colorectal and liver cancer, specifically the detection of lymph nodes and segmentation of the circumferential resection margin. In the second part of the paper, we shift attention to the complementary aspect of molecular image analysis, illustrating our approach with some recent work on: tumour acidosis, tumour hypoxia, and multiply drug resistant tumours.

  4. Quantitative Molecular Thermochemistry Based on Path Integrals

    SciTech Connect

    Glaesemann, K R; Fried, L E

    2005-03-14

    The calculation of thermochemical data requires accurate molecular energies and heat capacities. Traditional methods rely upon the standard harmonic normal mode analysis to calculate the vibrational and rotational contributions. We utilize path integral Monte Carlo (PIMC) for going beyond the harmonic analysis, to calculate the vibrational and rotational contributions to ab initio energies. This is an application and extension of a method previously developed in our group.

  5. Atomic force microscope, molecular imaging, and analysis.

    PubMed

    Chen, Shu-wen W; Teulon, Jean-Marie; Godon, Christian; Pellequer, Jean-Luc

    2016-01-01

    Image visibility is a central issue in analyzing all kinds of microscopic images. An increase of intensity contrast helps to raise the image visibility, thereby to reveal fine image features. Accordingly, a proper evaluation of results with current imaging parameters can be used for feedback on future imaging experiments. In this work, we have applied the Laplacian function of image intensity as either an additive component (Laplacian mask) or a multiplying factor (Laplacian weight) for enhancing image contrast of high-resolution AFM images of two molecular systems, an unknown protein imaged in air, provided by AFM COST Action TD1002 (http://www.afm4nanomedbio.eu/), and tobacco mosaic virus (TMV) particles imaged in liquid. Based on both visual inspection and quantitative representation of contrast measurements, we found that the Laplacian weight is more effective than the Laplacian mask for the unknown protein, whereas for the TMV system the strengthened Laplacian mask is superior to the Laplacian weight. The present results indicate that a mathematical function, as exemplified by the Laplacian function, may yield varied processing effects with different operations. To interpret the diversity of molecular structure and topology in images, an explicit expression for processing procedures should be included in scientific reports alongside instrumental setups. PMID:26224520

  6. Molecular Imaging of Experimental Abdominal Aortic Aneurysms

    PubMed Central

    Ramaswamy, Aneesh K.; Hamilton, Mark; Joshi, Rucha V.; Kline, Benjamin P.; Li, Rui; Wang, Pu; Goergen, Craig J.

    2013-01-01

    Current laboratory research in the field of abdominal aortic aneurysm (AAA) disease often utilizes small animal experimental models induced by genetic manipulation or chemical application. This has led to the use and development of multiple high-resolution molecular imaging modalities capable of tracking disease progression, quantifying the role of inflammation, and evaluating the effects of potential therapeutics. In vivo imaging reduces the number of research animals used, provides molecular and cellular information, and allows for longitudinal studies, a necessity when tracking vessel expansion in a single animal. This review outlines developments of both established and emerging molecular imaging techniques used to study AAA disease. Beyond the typical modalities used for anatomical imaging, which include ultrasound (US) and computed tomography (CT), previous molecular imaging efforts have used magnetic resonance (MR), near-infrared fluorescence (NIRF), bioluminescence, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Mouse and rat AAA models will hopefully provide insight into potential disease mechanisms, and the development of advanced molecular imaging techniques, if clinically useful, may have translational potential. These efforts could help improve the management of aneurysms and better evaluate the therapeutic potential of new treatments for human AAA disease. PMID:23737735

  7. Molecular Imaging of Inflammation in Atherosclerosis

    PubMed Central

    Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

    2013-01-01

    Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

  8. Inorganic nanoparticle-based contrast agents for molecular imaging

    PubMed Central

    Cho, Eun Chul; Glaus, Charles; Chen, Jingyi; Welch, Michael J.; Xia, Younan

    2010-01-01

    Inorganic nanoparticles including semiconductor quantum dots, iron oxide nanoparticles, and gold nanoparticles have been developed as contrast agents for diagnostics by molecular imaging. Compared to traditional contrast agents, nanoparticles offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size, and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multi-modal imaging. Here, we review recent advances in the development of contrast agents based on inorganic nanoparticles for molecular imaging, with a touch on contrast enhancement, surface modification, tissue targeting, clearance, and toxicity. As research efforts intensify, contrast agents based on inorganic nanoparticles that are highly sensitive, target-specific, and safe to use are expected to enter clinical applications in the near future. PMID:21074494

  9. Molecular Imaging Probe Development using Microfluidics

    PubMed Central

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

    2012-01-01

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

  10. In Vivo Molecular Imaging in Retinal Disease

    PubMed Central

    Xie, Fang; Luo, Wenting; Zhang, Zhongyu; Sun, Dawei

    2012-01-01

    There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of ocular fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule upregulation, some novel imaging agents that target retinal endothelial molecules were generated. In vivo molecular imaging has a great potential to impact medicine by detecting diseases or screening disease in early stages, identifying extent of disease, selecting disease and patient-specific therapeutic treatment, applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:22363836

  11. Molecular Imaging of Urogenital Diseases

    PubMed Central

    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

  12. Viewing angle analysis of integral imaging

    NASA Astrophysics Data System (ADS)

    Wang, Hong-Xia; Wu, Chun-Hong; Yang, Yang; Zhang, Lan

    2007-12-01

    Integral imaging (II) is a technique capable of displaying 3D images with continuous parallax in full natural color. It is becoming the most perspective technique in developing next generation three-dimensional TV (3DTV) and visualization field due to its outstanding advantages. However, most of conventional integral images are restricted by its narrow viewing angle. One reason is that the range in which a reconstructed integral image can be displayed with consistent parallax is limited. The other is that the aperture of system is finite. By far many methods , an integral imaging method to enhance the viewing angle of integral images has been proposed. Nevertheless, except Ren's MVW (Maximum Viewing Width) most of these methods involve complex hardware and modifications of optical system, which usually bring other disadvantages and make operation more difficult. At the same time the cost of these systems should be higher. In order to simplify optical systems, this paper systematically analyzes the viewing angle of traditional integral images instead of modified ones. Simultaneously for the sake of cost the research was based on computer generated integral images (CGII). With the analysis result we can know clearly how the viewing angle can be enhanced and how the image overlap or image flipping can be avoided. The result also promotes the development of optical instruments. Based on theoretical analysis, preliminary calculation was done to demonstrate how the other viewing properties which are closely related with the viewing angle, such as viewing distance, viewing zone, lens pitch, and etc. affect the viewing angle.

  13. Integrative System of Fast Photoacoustic Imaging

    NASA Astrophysics Data System (ADS)

    Yi, Tan

    An integrative fast (Photoacoustic) PA imaging system based on multi-element linear ultrasonic transducer array was developed, which integrates laser delivery, photoacoustic excitation and photoacoustic detection into a portable system. It collects PA signals by a multi-element linear transducer array in a reflection mode. The PA images with high spatial resolution and high contrast were obtained. Compared to other existing PA imaging methods, the integrative PA imaging system is characterized by rapidness, convenience and high practicality. The integrative system is mobile and portable, and it is suitable for imaging samples in natural condition with various different shapes. It will provide a novel and effective PA imaging approach for clinic diagnosis of neoplasm and tissue functional imaging in vivo, and has potential to be developed into a practical apparatus used in the early non-invasive detection of breast-cancer.

  14. Molecular and Functional Imaging of Internet Addiction

    PubMed Central

    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. PMID:25879023

  15. Accommodation response for integral photography still images

    NASA Astrophysics Data System (ADS)

    Yano, Sumio; Park, Min-Chul

    2015-05-01

    In this paper the accommodation responses for integral photography still images were measured. The experimental results showed that the accommodation responses for integral photography images showed a linear change with images showing the depth position of integral photography, even if the integral photography images were located out of the depth of the field. Furthermore, the discrimination of depth perception, which relates to a blur effect in integral photography images, was subjectively evaluated for the examination of its influence on the accommodation response. As a result, the range of the discrimination of depth perception was narrow in comparison to the range of the rectilinear accommodation response. However, these results were consistent according to the propensity of statistical significance for the discrimination of depth perception in the out range of subjectively effective discriminations.

  16. Progress in molecular imaging in endoscopy and endomicroscopy for cancer imaging.

    PubMed

    Khondee, Supang; Wang, Thomas D

    2013-01-01

    Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes. PMID:23502247

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

    PubMed Central

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    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. PMID:22180839

  18. Molecular Imaging with SERS-Active Nanoparticles

    PubMed Central

    Zhang, Yin; Hong, Hao; Myklejord, Duane V.; Cai, Weibo

    2011-01-01

    Lead-in Raman spectroscopy has been explored for various biomedical applications (e.g. cancer diagnosis) because it can provide detailed information on the chemical composition of cells and tissues. For imaging applications, several variations of Raman spectroscopy have been developed to enhance its sensitivity. To date, a wide variety of molecular targets and biological events have been investigated using surface-enhanced Raman scattering (SERS)-active nanoparticles. The superb multiplexing capability of SERS-based Raman imaging, already successfully demonstrated in live animals, can be extremely powerful in future research where different agents can be attached to different Raman tags to enable the simultaneous interrogation of multiple biological events. Over the last several years, molecular imaging with SERS-active nanoparticles has advanced significantly and many pivotal proof-of-principle experiments have been successfully carried out. It is expected that SERS-based imaging will continue to be a dynamic research field over the next decade. PMID:21932216

  19. Molecular imaging of cerebrovascular lesions.

    PubMed

    Chalouhi, Nohra; Jabbour, Pascal; Magnotta, Vincent; Hasan, David

    2014-04-01

    Inflammation is a key component in the pathogenesis of cerebrovascular lesions. Two agents have emerged as promising possibilities for imaging cerebrovascular lesions. These agents are ferumoxytol and myeloperoxidase (MPO)-specific paramagnetic magnetic resonance (MR) contrast agent. Ferumoxytol is an iron oxide nanoparticle coated by a carbohydrate shell that is used in MRI studies as an inflammatory marker as it is cleared by macrophages. Ferumoxytol-enhanced MRI allows noninvasive assessment of the inflammatory status of cerebral aneurysms and arteriovenous malformations and, possibly, may differentiate "unstable" lesions that require early intervention from "stable" lesions that can be safely observed. Several pilot studies have also suggested that MPO-specific paramagnetic MR contrast agent, di-5-hydroxytryptamide of gadopentetate dimeglumine, may allow imaging of inflammation in the wall of saccular aneurysms in animal models. However, studies in human subjects have yet to be performed. In this paper, we review current data regarding ferumoxytol-enhanced MRI and MPO-specific paramagnetic MR contrast agent and discuss current and future applications. PMID:24323714

  20. Molecular Probes for Fluorescence Lifetime Imaging

    PubMed Central

    Sarder, Pinaki; Maji, Dolonchampa; Achilefu, Samuel

    2015-01-01

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

  1. Functionalized gold nanorods for molecular optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Eghtedari, Mohammad; Oraevsky, Alexander; Conjusteau, Andre; Copland, John A.; Kotov, Nicholas A.; Motamedi, Massoud

    2007-02-01

    The development of gold nanoparticles for molecular optoacoustic imaging is a very promising area of research and development. Enhancement of optoacoustic imaging for molecular detection of tumors requires the engineering of nanoparticles with geometrical and molecular features that can enhance selective targeting of malignant cells while optimizing the sensitivity of optoacoustic detection. In this article, cylindrical gold nanoparticles (i.e. gold nanorods) were fabricated with a plasmon resonance frequency in the near infra-red region of the spectrum, where deep irradiation of tissue is possible using an Alexandrite laser. Gold nanorods (Au-NRs) were functionalized by covalent attachment of Poly(ethylene glycol) to enhance their biocompatibility. These particles were further functionalized with the aim of targeting breast cancer cells using monoclonal antibodies that binds to Her2/neu receptors, which are over expressed on the surface of breast cancer cells. A custom Laser Optoacoustic Imaging System (LOIS) was designed and employed to image nanoparticle-targeted cancer cells in a phantom and PEGylated Au-NRs that were injected subcutaneously into a nude mouse. The results of our experiments show that functionalized Au-NRs with a plasmon resonance frequency at near infra-red region of the spectrum can be detected and imaged in vivo using laser optoacoustic imaging system.

  2. Pretargeted molecular imaging and radioimmunotherapy.

    PubMed

    Goldenberg, David M; Chang, Chien-Hsing; Rossi, Edmund A; J, William; McBride; Sharkey, Robert M

    2012-01-01

    Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-hapten antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors. PMID:22737190

  3. Pretargeted Molecular Imaging and Radioimmunotherapy

    PubMed Central

    Goldenberg, David M.; Chang, Chien-Hsing; Rossi, Edmund A.; J, William; McBride; Sharkey, Robert M.

    2012-01-01

    Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-hapten antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors. PMID:22737190

  4. Stereoscopic Integrated Imaging Goggles for Multimodal Intraoperative Image Guidance

    PubMed Central

    Mela, Christopher A.; Patterson, Carrie; Thompson, William K.; Papay, Francis; Liu, Yang

    2015-01-01

    We have developed novel stereoscopic wearable multimodal intraoperative imaging and display systems entitled Integrated Imaging Goggles for guiding surgeries. The prototype systems offer real time stereoscopic fluorescence imaging and color reflectance imaging capacity, along with in vivo handheld microscopy and ultrasound imaging. With the Integrated Imaging Goggle, both wide-field fluorescence imaging and in vivo microscopy are provided. The real time ultrasound images can also be presented in the goggle display. Furthermore, real time goggle-to-goggle stereoscopic video sharing is demonstrated, which can greatly facilitate telemedicine. In this paper, the prototype systems are described, characterized and tested in surgeries in biological tissues ex vivo. We have found that the system can detect fluorescent targets with as low as 60 nM indocyanine green and can resolve structures down to 0.25 mm with large FOV stereoscopic imaging. The system has successfully guided simulated cancer surgeries in chicken. The Integrated Imaging Goggle is novel in 4 aspects: it is (a) the first wearable stereoscopic wide-field intraoperative fluorescence imaging and display system, (b) the first wearable system offering both large FOV and microscopic imaging simultaneously, (c) the first wearable system that offers both ultrasound imaging and fluorescence imaging capacities, and (d) the first demonstration of goggle-to-goggle communication to share stereoscopic views for medical guidance. PMID:26529249

  5. A Semantic Image Annotation Model to Enable Integrative Translational Research

    PubMed Central

    Rubin, Daniel L.; Mongkolwat, Pattanasak; Channin, David S.

    2009-01-01

    Integrating and relating images with clinical and molecular data is a crucial activity in translational research, but challenging because the information in images is not explicit in standard computer-accessible formats. We have developed an ontology-based representation of the semantic contents of radiology images called AIM (Annotation and Image Markup). AIM specifies the quantitative and qualitative content that researchers extract from images. The AIM ontology enables semantic image annotation and markup, specifying the entities and relations necessary to describe images. AIM annotations, represented as instances in the ontology, enable key use cases for images in translational research such as disease status assessment, query, and inter-observer variation analysis. AIM will enable ontology-based query and mining of images, and integration of images with data in other ontology-annotated bioinformatics databases. Our ultimate goal is to enable researchers to link images with related scientific data so they can learn the biological and physiological significance of the image content. PMID:21347180

  6. A Targeting Microbubble for Ultrasound Molecular Imaging

    PubMed Central

    Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

    2015-01-01

    Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

  7. Molecular specific optoacoustic imaging with plasmonic nanoparticles

    NASA Astrophysics Data System (ADS)

    Mallidi, Srivalleesha; Larson, Timothy; Aaron, Jesse; Sokolov, Konstantin; Emelianov, Stanislav

    2007-05-01

    Gold nanoparticles functionalized with antibodies can specifically bind to molecular biomarkers such as epithelial growth factor receptor (EGFR). The molecule specific nature of the antibody-functionalized gold nanoparticles forms the basis for the developed optoacoustic imaging technique to detect cancer at an asymptotic stage. Optoacoustic imaging was performed with 532 nm and 680 nm pulsed laser irradiation on three-dimensional tissue phantoms prepared using a human keratinocyte cell line. The results of our study demonstrate that the combination of anti-EGFR gold ioconjugates and optoacoustic imaging can allow highly sensitive and selective detection of human epithelial cancer cells.

  8. Microelectromechanical systems integrating molecular spin crossover actuators

    NASA Astrophysics Data System (ADS)

    Manrique-Juarez, Maria D.; Rat, Sylvain; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine

    2016-08-01

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H2B(pz)2)2(phen)] (H2B(pz)2 = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δfr = -0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  9. Imaging performance of a miniature integrated microendoscope

    PubMed Central

    Rogers, Jeremy D.; Landau, Sara; Tkaczyk, Tomasz S.; Descour, Michael R.; Rahman, Mohammed S.; Richards-Kortum, Rebecca; Kärkäinen, Ari H. O.; Christenson, Todd

    2011-01-01

    An integrated miniature multi-modal microscope (4M device) for microendoscopy was built and tested. Imaging performance is evaluated and imaging results are presented for both fluorescence and reflectance samples. Images of biological samples show successful imaging of both thin layers of fixed cells prepared on a slide as well as thick samples of excised fixed porcine epithelial tissue, thus demonstrating the potential for in vivo use. PMID:19021400

  10. Protein-based tumor molecular imaging probes

    PubMed Central

    Lin, Xin; Xie, Jin

    2013-01-01

    Molecular imaging is an emerging discipline which plays critical roles in diagnosis and therapeutics. It visualizes and quantifies markers that are aberrantly expressed during the disease origin and development. Protein molecules remain to be one major class of imaging probes, and the option has been widely diversified due to the recent advances in protein engineering techniques. Antibodies are part of the immunosystem which interact with target antigens with high specificity and affinity. They have long been investigated as imaging probes and were coupled with imaging motifs such as radioisotopes for that purpose. However, the relatively large size of antibodies leads to a half-life that is too long for common imaging purposes. Besides, it may also cause a poor tissue penetration rate and thus compromise some medical applications. It is under this context that various engineered protein probes, essentially antibody fragments, protein scaffolds, and natural ligands have been developed. Compared to intact antibodies, they possess more compact size, shorter clearance time, and better tumor penetration. One major challenge of using protein probes in molecular imaging is the affected biological activity resulted from random labeling. Site-specific modification, however, allows conjugation happening in a stoichiometric fashion with little perturbation of protein activity. The present review will discuss protein-based probes with focus on their application and related site-specific conjugation strategies in tumor imaging. PMID:20232092

  11. Authenticity and integrity of digital mammography images.

    PubMed

    Zhou, X Q; Huang, H K; Lou, S L

    2001-08-01

    Data security becomes more and more important in telemammography which uses a public high-speed wide area network connecting the examination site with the mammography expert center. Generally, security is characterized in terms of privacy, authenticity and integrity of digital data. Privacy is a network access issue and is not considered in this paper. We present a method, authenticity and integrity of digital mammography, here which can meet the requirements of authenticity and integrity for mammography image (IM) transmission. The authenticity and integrity for mammography (AIDM) consists of the following four modules. 1) Image preprocessing: To segment breast pixels from background and extract patient information from digital imaging and communication in medicine (DICOM) image header. 2) Image hashing: To compute an image hash value of the mammogram using the MD5 hash algorithm. 3) Data encryption: To produce a digital envelope containing the encrypted image hash value (digital signature) and corresponding patient information. 4) Data embedding: To embed the digital envelope into the image. This is done by replacing the least significant bit of a random pixel of the mammogram by one bit of the digital envelope bit stream and repeating for all bits in the bit stream. Experiments with digital IMs demonstrate the following. 1) In the expert center, only the user who knows the private key can open the digital envelope and read the patient information data and the digital signature of the mammogram transmitted from the examination site. 2) Data integrity can be verified by matching the image hash value decrypted from the digital signature with that computed from the transmitted image. 3) No visual quality degradation is detected in the embedded image compared with the original. Our preliminary results demonstrate that AIDM is an effective method for image authenticity and integrity in telemammography application. PMID:11513029

  12. Dose reduction in molecular breast imaging

    NASA Astrophysics Data System (ADS)

    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.

  13. VA's Integrated Imaging System on three platforms.

    PubMed

    Dayhoff, R E; Maloney, D L; Majurski, W J

    1992-01-01

    The DHCP Integrated Imaging System provides users with integrated patient data including text, image and graphics data. This system has been transferred from its original two screen DOS-based MUMPS platform to an X window workstation and a Microsoft Windows-based workstation. There are differences between these various platforms that impact on software design and on software development strategy. Data structures and conventions were used to isolate hardware, operating system, imaging software, and user-interface differences between platforms in the implementation of functionality for text and image display and interaction. The use of an object-oriented approach greatly increased system portability. PMID:1482983

  14. Stereoscopic Integrated Imaging Goggles for Multimodal Intraoperative Image Guidance.

    PubMed

    Mela, Christopher A; Patterson, Carrie; Thompson, William K; Papay, Francis; Liu, Yang

    2015-01-01

    We have developed novel stereoscopic wearable multimodal intraoperative imaging and display systems entitled Integrated Imaging Goggles for guiding surgeries. The prototype systems offer real time stereoscopic fluorescence imaging and color reflectance imaging capacity, along with in vivo handheld microscopy and ultrasound imaging. With the Integrated Imaging Goggle, both wide-field fluorescence imaging and in vivo microscopy are provided. The real time ultrasound images can also be presented in the goggle display. Furthermore, real time goggle-to-goggle stereoscopic video sharing is demonstrated, which can greatly facilitate telemedicine. In this paper, the prototype systems are described, characterized and tested in surgeries in biological tissues ex vivo. We have found that the system can detect fluorescent targets with as low as 60 nM indocyanine green and can resolve structures down to 0.25 mm with large FOV stereoscopic imaging. The system has successfully guided simulated cancer surgeries in chicken. The Integrated Imaging Goggle is novel in 4 aspects: it is (a) the first wearable stereoscopic wide-field intraoperative fluorescence imaging and display system, (b) the first wearable system offering both large FOV and microscopic imaging simultaneously, PMID:26529249

  15. Cerenkov imaging - a new modality for molecular imaging

    PubMed Central

    Thorek, Daniel LJ; Robertson, Robbie; Bacchus, Wassifa A; Hahn, Jaeseung; Rothberg, Julie; Beattie, Bradley J; Grimm, Jan

    2012-01-01

    Cerenkov luminescence imaging (CLI) is an emerging hybrid modality that utilizes the light emission from many commonly used medical isotopes. Cerenkov radiation (CR) is produced when charged particles travel through a dielectric medium faster than the speed of light in that medium. First described in detail nearly 100 years ago, CR has only recently applied for biomedical imaging purposes. The modality is of considerable interest as it enables the use of widespread luminescence imaging equipment to visualize clinical diagnostic (all PET radioisotopes) and many therapeutic radionuclides. The amount of light detected in CLI applications is significantly lower than other that in other optical imaging techniques such as bioluminescence and fluorescence. However, significant advantages include the use of approved radiotracers and lack of an incident light source, resulting in high signal to background ratios. As well, multiple subjects may be imaged concurrently (up to 5 in common bioluminescent equipment), conferring both cost and time benefits. This review summarizes the field of Cerenkov luminescence imaging to date. Applications of CLI discussed include intraoperative radionuclide-guided surgery, monitoring of therapeutic efficacy, tomographic optical imaging capabilities, and the ability to perform multiplexed imaging using fluorophores excited by the Cerenkov radiation. While technical challenges still exist, Cerenkov imaging has materialized as an important molecular imaging modality. PMID:23133811

  16. Integrated image information management: research issues

    NASA Astrophysics Data System (ADS)

    Mehrotra, Rajiv; Pierson, William E., Jr.

    1995-06-01

    A vast number of applications including defense, medical, manufacturing, law enforcement, digital library, education, space exploration, weather forecasting, and entertainment require efficient management of huge collections of nonalphanumeric data. The most common and important nonalphanumeric data in most of these applications is image data. Owing to the availability of a variety of visual sensors, several large collections of images and related anciliary data exists and are rapidly growing. Examples of such collections include LANDSAT, weather, medical, and DoD target signature images. Unfortunately, in most cases only a fraction of the collected data is ever utilized to its full potential. The primary reason for this under-utilization is the lack of pictorial data management techniques/systems. Conventional data management systems are not designed to handle pictorial data in an integrated fashion, i.e., images and alphanumeric data are not treated equally. In such systems, an image is stored as a tag field in the description of some entity. Images are not entities and they cannot be key fields. Furthermore, content-based retrieval of images and related data is not possible. Therefore, new data management technologies need to be developed for an integrated management of textual and imagery data. This requires a clear understanding of the requirements and desireable characteristics of a pictorial data management system. In almost all image information management (or integrated image database) applications, image information modeling, content-based image information retrieval, and memeory management are the most important issues to be resolved. In this paper, the requirements of an integrated image information management system and the challenges posed by image data from the data modeling, the content-based retrieval, and the memory management viewpoints are discussed.

  17. Intelligent Design of Nano-Scale Molecular Imaging Agents

    PubMed Central

    Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

    2012-01-01

    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. PMID:23235326

  18. Integrated infrared and visible image sensors

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Pain, Bedabrata (Inventor)

    2000-01-01

    Semiconductor imaging devices integrating an array of visible detectors and another array of infrared detectors into a single module to simultaneously detect both the visible and infrared radiation of an input image. The visible detectors and the infrared detectors may be formed either on two separate substrates or on the same substrate by interleaving visible and infrared detectors.

  19. Three Dimensional Molecular Imaging for Lignocellulosic Materials

    SciTech Connect

    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.

  20. Translational Molecular Imaging of Prostate Cancer

    PubMed Central

    Kiess, Ana P.; Cho, Steve Y.; Pomper, Martin G.

    2013-01-01

    Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. 99mTc bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer. PMID:24159427

  1. Molecular Imaging of Biomarkers in Breast Cancer

    PubMed Central

    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

  2. Hybrid imaging is the future of molecular imaging

    PubMed Central

    Hicks, RJ; Lau, EWF; Binns, DS

    2007-01-01

    Correlative imaging has long been used in clinical practice and particularly for the interpretation of nuclear medicine studies wherein detailed anatomical information is often lacking. Previously, side-by-side comparison or software co-registration techniques were applied but suffered from technical limitations related to the differing geometries of the imaging equipment, differences in the positioning of patients and displacement of mobile structures between studies. The development of the first hybrid PET and CT device struck a chord with the medical imaging community that is still ringing loudly throughout the world. So successful has been the concept of PET-CT that none of the major medical imaging manufacturers now offers stand-alone PET scanners. Following close behind this success, SPECT-CT devices have recently been adopted by the nuclear medicine community, already compelled by the benefits of hybrid imaging through their experience with PET-CT. Recent reports of adaptation of PET detectors to operate within the strong magnetic field of MRI scanners have generated further enthusiasm. Prototype PET-MRI devices are now in development. The complementary anatomical, functional and molecular information provided by these techniques can now be presented in an intuitive and aesthetically-pleasing format. This has made end-users more comfortable with the results of functional imaging techniques than when the same information is presented independently. Despite the primacy of anatomical imaging for locoregional disease definition, the molecular characterisation available from PET and SPECT offers unique complementary information for cancer evaluation. A new era of cancer imaging, when hybrid imaging will be the primary diagnostic tool, is approaching. PMID:21614291

  3. MR Molecular Imaging of Tumor Vasculature and Vascular Targets

    PubMed Central

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

    2016-01-01

    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from “bench to bedside”. The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. PMID:20807600

  4. Molecular imaging with surface-enhanced Raman spectroscopy nanoparticle reporters

    PubMed Central

    Jokerst, Jesse V.; Pohling, Christoph; Gambhir, Sanjiv S.

    2013-01-01

    Molecular imaging scans cellular and molecular targets in living subjects through the introduction of imaging agents that bind to these targets and report their presence through a measurable signal. The picomolar sensitivity, signal stability, and high multiplexing capacity of Raman spectroscopy satisfies important needs within the field of molecular imaging, and several groups now utilize Raman and surface-enhanced Raman spectroscopy to image molecular targets in small animal models of human disease. This article details the role of Raman spectroscopy in molecular imaging, describes some substrates and imaging agents used in animal models, and illustrates some examples. PMID:24293809

  5. Precision Imaging: more descriptive, predictive and integrative imaging.

    PubMed

    Frangi, Alejandro F; Taylor, Zeike A; Gooya, Ali

    2016-10-01

    Medical image analysis has grown into a matured field challenged by progress made across all medical imaging technologies and more recent breakthroughs in biological imaging. The cross-fertilisation between medical image analysis, biomedical imaging physics and technology, and domain knowledge from medicine and biology has spurred a truly interdisciplinary effort that stretched outside the original boundaries of the disciplines that gave birth to this field and created stimulating and enriching synergies. Consideration on how the field has evolved and the experience of the work carried out over the last 15 years in our centre, has led us to envision a future emphasis of medical imaging in Precision Imaging. Precision Imaging is not a new discipline but rather a distinct emphasis in medical imaging borne at the cross-roads between, and unifying the efforts behind mechanistic and phenomenological model-based imaging. It captures three main directions in the effort to deal with the information deluge in imaging sciences, and thus achieve wisdom from data, information, and knowledge. Precision Imaging is finally characterised by being descriptive, predictive and integrative about the imaged object. This paper provides a brief and personal perspective on how the field has evolved, summarises and formalises our vision of Precision Imaging for Precision Medicine, and highlights some connections with past research and current trends in the field. PMID:27373145

  6. Compact integral three-dimensional imaging device

    NASA Astrophysics Data System (ADS)

    Arai, J.; Yamashita, T.; Hiura, H.; Miura, M.; Funatsu, R.; Nakamura, T.; Nakasu, E.

    2015-05-01

    A compact integral three-dimensional (3D) imaging device for capturing high resolution 3D images has been developed that positions the lens array and image sensor close together. Unlike the conventional scheme, where a camera lens is used to project the elemental images generated by the lens array onto the image sensor, the developed device combines the lens array and image sensor into one unit and makes no use of a camera lens. In order to capture high resolution 3D images, a high resolution imaging sensor and a lens array composed of many elemental lenses are required, and in an experimental setup, a CMOS image sensor circuit patterned with multiple exposures and a multiple lens array were used. Two types of optics were implemented for controlling the depth of 3D images. The first type was a convex lens that is suitable for compressing a relatively large object space, and the second was an afocal lens array that is suitable for capturing a relatively small object space without depth distortion. The objects captured with the imaging device and depth control optics were reconstructed as 3D images by using display equipment consisting of a liquid crystal panel and a lens array. The reconstructed images were found to have appropriate motion parallax.

  7. Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine

    PubMed Central

    Sevick-Muraca, Eva M.; Rasmussen, John C.

    2010-01-01

    We compare and contrast the development of optical molecular imaging techniques with nuclear medicine with a didactic emphasis for initiating readers into the field of molecular imaging. The nuclear imaging techniques of gamma scintigraphy, single-photon emission computed tomography, and positron emission tomography are first briefly reviewed. The molecular optical imaging techniques of bioluminescence and fluorescence using gene reporter/probes and gene reporters are described prior to introducing the governing factors of autofluorescence and excitation light leakage. The use of dual-labeled, near-infrared excitable and radio-labeled agents are described with comparative measurements between planar fluorescence and nuclear molecular imaging. The concept of time-independent and -dependent measurements is described with emphasis on integrating time-dependent measurements made in the frequency domain for 3-D tomography. Finally, we comment on the challenges and progress for translating near-infrared (NIR) molecular imaging agents for personalized medicine. PMID:19021311

  8. Molecular Breast Imaging Using Emission Tomosynthesis

    SciTech Connect

    Gopan, O.; Gilland, D.; Weisenberger, Andrew G.; Kross, Brian J.; Welch, Benjamin L.

    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

  9. Comprehensive phantom for interventional fluorescence molecular imaging.

    PubMed

    Anastasopoulou, Maria; Koch, Maximilian; Gorpas, Dimitris; Karlas, Angelos; Klemm, Uwe; Garcia-Allende, Pilar Beatriz; Ntziachristos, Vasilis

    2016-09-01

    Fluorescence imaging has been considered for over a half-century as a modality that could assist surgical guidance and visualization. The administration of fluorescent molecules with sensitivity to disease biomarkers and their imaging using a fluorescence camera can outline pathophysiological parameters of tissue invisible to the human eye during operation. The advent of fluorescent agents that target specific cellular responses and molecular pathways of disease has facilitated the intraoperative identification of cancer with improved sensitivity and specificity over nonspecific fluorescent dyes that only outline the vascular system and enhanced permeability effects. With these new abilities come unique requirements for developing phantoms to calibrate imaging systems and algorithms. We briefly review herein progress with fluorescence phantoms employed to validate fluorescence imaging systems and results. We identify current limitations and discuss the level of phantom complexity that may be required for developing a universal strategy for fluorescence imaging calibration. Finally, we present a phantom design that could be used as a tool for interlaboratory system performance evaluation. PMID:27304578

  10. PET Imaging - from Physics to Clinical Molecular Imaging

    NASA Astrophysics Data System (ADS)

    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.

  11. Combining Optical Coherence Tomography with Fluorescence Molecular Imaging: Towards Simultaneous Morphology and Molecular Imaging

    PubMed Central

    Yuan, Shuai; Roney, Celeste A.; Wierwille, Jerry; Chen, Chao-Wei; Xu, Biying; Jiang, James; Ma, Hongzhou; Cable, Alex; Summers, Ronald M.; Chen, Yu

    2010-01-01

    Optical coherence tomography (OCT) provides high-resolution, cross-sectional imaging of tissue microstructure in situ and in real-time, while fluorescence molecular imaging (FMI) enables the visualization of basic molecular processes. There are great interests in combining these two modalities so that the tissue's structural and molecular information can be obtained simultaneously. This could greatly benefit biomedical applications such as detecting early diseases and monitoring therapeutic interventions. In this research, an optical system that combines OCT and FMI was developed. The system demonstrated that it could co-register en face OCT and FMI images with a 2.4 × 2.4 mm field of view. The transverse resolutions of OCT and FMI of the system are both ~10 μm. Capillary tubes filled with fluorescent dye Cy 5.5 in different concentrations under a scattering medium are used as the phantom. En face OCT images of the phantoms were obtained and successfully co-registered with FMI images that were acquired simultaneously. A linear relationship between FMI intensity and dye concentration was observed. The relationship between FMI intensity and target fluorescence tube depth measured by OCT images was also observed and compared with theoretical modeling. This relationship could help in correcting reconstructed dye concentration. Imaging of colon polyps of APCmin mouse model is presented as an example of biological applications of this co-registered OCT/FMI system. PMID:20009192

  12. The system integration of image processing

    NASA Astrophysics Data System (ADS)

    Chen, Qi-xing; Wu, Qin-zhang; Gao, Xiao-dong; Ren, Guo-qiang

    2008-03-01

    An integration system was designed to apply to the remote communication of optics and electronics detection systems, which was integrated with programmable DSP and FPGA chirps in addition to a few Application Specific Integrated Circuits (ASICs). It could achieve image binarization, image enhancement, data encryption, image compression encoding, channel encoding, data interleaving, etc., and the algorithms of these functions might be renewed or updated easily. The CCD color camera being a signal source, experiments had been done on the platform with a DSP chirp and a FPGA one. The FPGA chirp mainly realized the reconstruction of image's brightness signal and the production of various timing signals, and the DSP chirp mainly accomplished the other functions. The algorithms to compress image data were based on discrete cosine transformation (DCT) and discrete wavelet transformation (DWT), respectively. The experiment results showed that the developed platform was characterized by flexibility, programmability and reconfigurability. The integration system is well suitable for the remote communication of optics and electronics detection systems.

  13. Molecular probes for malignant melanoma imaging.

    PubMed

    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

  14. Optimal integration time in OCT imaging

    NASA Astrophysics Data System (ADS)

    Martin, Lorenz; Gräub, Stephan; Meier, Christoph

    2015-07-01

    When measuring static objects with 3D OCT, two opposing trends occur: If the integration time is too short, the measurement is noisy resulting in granulated textures on measured objects. If the integration time is too long, drifts e.g. due to thermal effects or unstable laser sources lead to blurred images. The Allan variance is a scheme to find the optimal integration time in terms of reducing noise without picking up signal drift. A long-term measurement with short integration time of a reference target under realistic conditions is needed to obtain the database for the calculation of the Allan variance. Longer integration times are simulated by taking averages of subsequent samples. The Allan variance being the mean of the squared differences between two consecutive averages is calculated for different integration times. The optimal integration time is achieved for minimal Allan variance. First, the scheme is explained and discussed with simulated data. Then, reference measurements of layers of adhesive tape made with a 3D OCT device are analysed to find the optimal integration time of the device. Finally, the findings are applied to the detection of water inclusions in calcite. With too short integration time the water inclusions appear with a stained surface. With the integration time increased towards the optimal time, the surfaces of the water inclusions get smoother and easier to discriminate from the background. Ready-to-use Octave code for the computation of the Allan variance is provided.

  15. An Integrated Imaging Detector of Polarization and Spectral Content

    NASA Technical Reports Server (NTRS)

    Rust, D. M.; Thompson, K. E.

    1993-01-01

    A new type of image detector has been designed to simultaneously analyze the polarization of light at all picture elements in a scene. The Integrated Dual Imaging Detector (IDID) consists of a polarizing beamsplitter bonded to a charge-coupled device (CCD), with signal-analysis circuitry and analog-to-digital converters, all integrated on a silicon chip. It should be capable of 1:10(exp 4) polarization discrimination. The IDID should simplify the design and operation of imaging polarimeters and spectroscopic imagers used, for example, in atmospheric and solar research. Innovations in the IDID include (1) two interleaved 512 x 1024-pixel imaging arrays (one for each polarization plane); (2) large dynamic range (well depth of 10(exp 6) electrons per pixel); (3) simultaneous readout of both images at 10 million pixels per second each; (4) on-chip analog signal processing to produce polarization maps in real time; (5) on-chip 10-bit A/D conversion. When used with a lithium-niobate Fabry-Perot etalon or other color filter that can encode spectral information as polarization, the IDID can collect and analyze simultaneous images at two wavelengths. Precise photometric analysis of molecular or atomic concentrations in the atmosphere is one suggested application. When used in a solar telescope, the IDID will charge the polarization, which can then be converted to maps of the vector magnetic fields on the solar surface.

  16. Molecular imaging of in vivo gene expression

    PubMed Central

    Harney, Allison S.; Meade, Thomas J.

    2015-01-01

    Background Advances in imaging technologies have taken a prominent role in experimental and translational research and provide essential information on how changes in gene expression are related to downstream developmental and disease states. Discussion Magnetic resonance imaging contrast agents and optical probes developed to enhance signal intensity in the presence of a specific enzyme, genetic marker, second messenger or metabolite can prove a facile method of advancing the understanding of molecular events in disease progression. Conclusion The ability to detect changes in gene expression at the early stages of disease will lead to a greater understanding of disease progression, the use of early therapeutic intervention to increase patient survival, and tailored therapies to the detected genetic alterations in individual patients. PMID:21426178

  17. Integrated wavelets for medical image analysis

    NASA Astrophysics Data System (ADS)

    Heinlein, Peter; Schneider, Wilfried

    2003-11-01

    Integrated wavelets are a new method for discretizing the continuous wavelet transform (CWT). Independent of the choice of discrete scale and orientation parameters they yield tight families of convolution operators. Thus these families can easily be adapted to specific problems. After presenting the fundamental ideas, we focus primarily on the construction of directional integrated wavelets and their application to medical images. We state an exact algorithm for implementing this transform and present applications from the field of digital mammography. The first application covers the enhancement of microcalcifications in digital mammograms. Further, we exploit the directional information provided by integrated wavelets for better separation of microcalcifications from similar structures.

  18. Information and image integration: project spectrum

    NASA Astrophysics Data System (ADS)

    Blaine, G. James; Jost, R. Gilbert; Martin, Lori; Weiss, David A.; Lehmann, Ron; Fritz, Kevin

    1998-07-01

    The BJC Health System (BJC) and the Washington University School of Medicine (WUSM) formed a technology alliance with industry collaborators to develop and implement an integrated, advanced clinical information system. The industry collaborators include IBM, Kodak, SBC and Motorola. The activity, called Project Spectrum, provides an integrated clinical repository for the multiple hospital facilities of the BJC. The BJC System consists of 12 acute care hospitals serving over one million patients in Missouri and Illinois. An interface engine manages transactions from each of the hospital information systems, lab systems and radiology information systems. Data is normalized to provide a consistent view for the primary care physician. Access to the clinical repository is supported by web-based server/browser technology which delivers patient data to the physician's desktop. An HL7 based messaging system coordinates the acquisition and management of radiological image data and sends image keys to the clinical data repository. Access to the clinical chart browser currently provides radiology reports, laboratory data, vital signs and transcribed medical reports. A chart metaphor provides tabs for the selection of the clinical record for review. Activation of the radiology tab facilitates a standardized view of radiology reports and provides an icon used to initiate retrieval of available radiology images. The selection of the image icon spawns an image browser plug-in and utilizes the image key from the clinical repository to access the image server for the requested image data. The Spectrum system is collecting clinical data from five hospital systems and imaging data from two hospitals. Domain specific radiology imaging systems support the acquisition and primary interpretation of radiology exams. The spectrum clinical workstations are deployed to over 200 sites utilizing local area networks and ISDN connectivity.

  19. Symbolic programming language in molecular multicenter integral problem

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Bouferguene, Ahmed

    It is well known that in any ab initio molecular orbital (MO) calculation, the major task involves the computation of molecular integrals, among which the computation of three-center nuclear attraction and Coulomb integrals is the most frequently encountered. As the molecular system becomes larger, computation of these integrals becomes one of the most laborious and time-consuming steps in molecular systems calculation. Improvement of the computational methods of molecular integrals would be indispensable to further development in computational studies of large molecular systems. To develop fast and accurate algorithms for the numerical evaluation of these integrals over B functions, we used nonlinear transformations for improving convergence of highly oscillatory integrals. These methods form the basis of new methods for solving various problems that were unsolvable otherwise and have many applications as well. To apply these nonlinear transformations, the integrands should satisfy linear differential equations with coefficients having asymptotic power series in the sense of Poincaré, which in their turn should satisfy some limit conditions. These differential equations are very difficult to obtain explicitly. In the case of molecular integrals, we used a symbolic programming language (MAPLE) to demonstrate that all the conditions required to apply these nonlinear transformation methods are satisfied. Differential equations are obtained explicitly, allowing us to demonstrate that the limit conditions are also satisfied.

  20. See-through integral imaging display with background occlusion capability.

    PubMed

    Yamaguchi, Yuta; Takaki, Yasuhiro

    2016-01-20

    Background occlusion capability is provided to a flat-panel-type integral imaging display that has a transparent screen and can superimpose three-dimensional (3D) images on real scenes. A symmetric integral imaging system that comprises two integral imaging systems connected by an additional lens array, is proposed. Elementary images are displayed on a flat-panel display on one integral imaging system to generate 3D images, and the occlusion mask patterns are displayed on a flat-panel display on the other integral imaging system to selectively block rays from background scenes. The proposed system was constructed and experimentally verified. PMID:26835946

  1. Molecular Imaging with MRI: Potential Application in Pancreatic Cancer

    PubMed Central

    Chen, Chen; Wu, Chang Qiang; Chen, Tian Wu; Tang, Meng Yue; Zhang, Xiao Ming

    2015-01-01

    Despite the variety of approaches that have been improved to achieve a good understanding of pancreatic cancer (PC), the prognosis of PC remains poor, and the survival rates are dismal. The lack of early detection and effective interventions is the main reason. Therefore, considerable ongoing efforts aimed at identifying early PC are currently being pursued using a variety of methods. In recent years, the development of molecular imaging has made the specific targeting of PC in the early stage possible. Molecular imaging seeks to directly visualize, characterize, and measure biological processes at the molecular and cellular levels. Among different imaging technologies, the magnetic resonance (MR) molecular imaging has potential in this regard because it facilitates noninvasive, target-specific imaging of PC. This topic is reviewed in terms of the contrast agents for MR molecular imaging, the biomarkers related to PC, targeted molecular probes for MRI, and the application of MRI in the diagnosis of PC. PMID:26579537

  2. Current Progress of Aptamer-Based Molecular Imaging

    PubMed Central

    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. PMID:24525205

  3. Progress in 3D imaging and display by integral imaging

    NASA Astrophysics Data System (ADS)

    Martinez-Cuenca, R.; Saavedra, G.; Martinez-Corral, M.; Pons, A.; Javidi, B.

    2009-05-01

    Three-dimensionality is currently considered an important added value in imaging devices, and therefore the search for an optimum 3D imaging and display technique is a hot topic that is attracting important research efforts. As main value, 3D monitors should provide the observers with different perspectives of a 3D scene by simply varying the head position. Three-dimensional imaging techniques have the potential to establish a future mass-market in the fields of entertainment and communications. Integral imaging (InI), which can capture true 3D color images, has been seen as the right technology to 3D viewing to audiences of more than one person. Due to the advanced degree of development, InI technology could be ready for commercialization in the coming years. This development is the result of a strong research effort performed along the past few years by many groups. Since Integral Imaging is still an emerging technology, the first aim of the "3D Imaging and Display Laboratory" at the University of Valencia, has been the realization of a thorough study of the principles that govern its operation. Is remarkable that some of these principles have been recognized and characterized by our group. Other contributions of our research have been addressed to overcome some of the classical limitations of InI systems, like the limited depth of field (in pickup and in display), the poor axial and lateral resolution, the pseudoscopic-to-orthoscopic conversion, the production of 3D images with continuous relief, or the limited range of viewing angles of InI monitors.

  4. Molecular imaging probes derived from natural peptides.

    PubMed

    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

  5. Developing MR probes for molecular imaging.

    PubMed

    McMahon, Michael T; Chan, Kannie W Y

    2014-01-01

    Molecular imaging plays an important role in the era of personalized medicine, especially with recent advances in magnetic resonance (MR) probes. While the first generation of these probes focused on maximizing contrast enhancement, a second generation of probes has been developed to improve the accumulation within specific tissues or pathologies, and the newest generation of agents is also designed to report on changes in physiological status and has been termed "smart" agents. This represents a paradigm switch from the previously commercialized gadolinium and iron oxide probes to probes with new capabilities, and leads to new challenges as scanner hardware needs to be adapted for detecting these probes. In this chapter, we highlight the unique features for all five different categories of MR probes, including the emerging chemical exchange saturation transfer, (19)F, and hyperpolarized probes, and describe the key physical properties and features motivating their design. As part of this comparison, the strengths and weaknesses of each category are discussed. PMID:25287693

  6. Molecular hydrogen polarization images of OMC-1

    SciTech Connect

    Burton, M.G.; Minchin, N.R.; Hough, J.H.; Aspin, C.; Axon, D.J. California Univ., Irvine Hatfield Polytechnic Joint Astronomy Centre, Hilo, HI Nuffield Radio Astronomy Labs., Jodrell Bank )

    1991-07-01

    An image of the polarization of the shocked H2 v = 1-0 S(1) line emission in the core of OMC-1 has been obtained. Along the molecular outflow of the source, the line is dichroically polarized by a medium of aligned grains located between the earth and the shock fronts. The polarization pattern traces the magnetic field direction, which is parallel to the outflow axis and to the large-scale field direction determined from far-IR continuum measurements. Close to the IR source IRc2, the likely source of the outflow, the aligned vectors twist, indicating that the magnetic field direction changes. Modeling the line ratios of scattered H2 lines in the reflection nebula, it is concluded that the size distribution of grains there is typical of the small grains in the diffuse interstellar medium. By contrast, the scattered continuum radiation from the core region suggests that the grains there are larger than this. 33 refs.

  7. Molecular hydrogen polarization images of OMC-1

    NASA Technical Reports Server (NTRS)

    Burton, Michael G.; Minchin, N. R.; Hough, J. H.; Aspin, C.; Axon, D. J.

    1991-01-01

    An image of the polarization of the shocked H2 v = 1-0 S(1) line emission in the core of OMC-1 has been obtained. Along the molecular outflow of the source, the line is dichroically polarized by a medium of aligned grains located between the earth and the shock fronts. The polarization pattern traces the magnetic field direction, which is parallel to the outflow axis and to the large-scale field direction determined from far-IR continuum measurements. Close to the IR source IRc2, the likely source of the outflow, the aligned vectors twist, indicating that the magnetic field direction changes. Modeling the line ratios of scattered H2 lines in the reflection nebula, it is concluded that the size distribution of grains there is typical of the small grains in the diffuse interstellar medium. By contrast, the scattered continuum radiation from the core region suggests that the grains there are larger than this.

  8. Computational methods for optical molecular imaging

    PubMed Central

    Chen, Duan; Wei, Guo-Wei; Cong, Wen-Xiang; Wang, Ge

    2010-01-01

    Summary A new computational technique, the matched interface and boundary (MIB) method, is presented to model the photon propagation in biological tissue for the optical molecular imaging. Optical properties have significant differences in different organs of small animals, resulting in discontinuous coefficients in the diffusion equation model. Complex organ shape of small animal induces singularities of the geometric model as well. The MIB method is designed as a dimension splitting approach to decompose a multidimensional interface problem into one-dimensional ones. The methodology simplifies the topological relation near an interface and is able to handle discontinuous coefficients and complex interfaces with geometric singularities. In the present MIB method, both the interface jump condition and the photon flux jump conditions are rigorously enforced at the interface location by using only the lowest-order jump conditions. This solution near the interface is smoothly extended across the interface so that central finite difference schemes can be employed without the loss of accuracy. A wide range of numerical experiments are carried out to validate the proposed MIB method. The second-order convergence is maintained in all benchmark problems. The fourth-order convergence is also demonstrated for some three-dimensional problems. The robustness of the proposed method over the variable strength of the linear term of the diffusion equation is also examined. The performance of the present approach is compared with that of the standard finite element method. The numerical study indicates that the proposed method is a potentially efficient and robust approach for the optical molecular imaging. PMID:20485461

  9. Molecular Ultrasound Imaging: Current Status and Future Directions

    PubMed Central

    Deshpande, Nirupama; Needles, Andrew; Willmann, Jürgen K.

    2011-01-01

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionizing irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of preclinical and clinical ultrasound systems , the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic. PMID:20541656

  10. The advancing clinical impact of molecular imaging in CVD.

    PubMed

    Osborn, Eric A; Jaffer, Farouc A

    2013-12-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging), as well as in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in phase II clinical trials. Here, we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  11. Molecular breast imaging with gamma emitters.

    PubMed

    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

  12. 802GHz integrated horn antennas imaging array

    NASA Astrophysics Data System (ADS)

    Ali-Ahmad, Walid Y.; Rebeiz, Gabriel M.; Dave, Hemant; Chin, Gordon

    1991-05-01

    Pattern measurements at 802GHz of a single element in 256-element integrated horn imaging array are presented. The integrated-horn antenna consists of a dipole-antenna suspended on a 1-micron dielectric membrane inside a pyramidal cavity etched in silicon. The theoretical far-field patterns, calculated using reciprocity and Floquet-modes representation of the free-space field, agree well with the measured far-field patterns at 802GHz. The associated directivity for a 1.40 lambda horn aperture, calculated from the measured E and H-plane patterns is 12.3dB + or - 0.2dB. This work demonstrates that high-efficiency integrated-horn antennas are easily scalable to terahertz frequencies and could be used for radio-astronomical and plasma-diagnostic applications.

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

    PubMed

    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

  14. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

    PubMed Central

    Psaltis, Peter J.

    2016-01-01

    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 18Fluoride 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 18Fluoride 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-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093

  15. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  16. Development and integration of Raman imaging capabilities to Sandia National Laboratories hyperspectral fluorescence imaging instrument.

    SciTech Connect

    Timlin, Jerilyn Ann; Nieman, Linda T.

    2005-11-01

    Raman spectroscopic imaging is a powerful technique for visualizing chemical differences within a variety of samples based on the interaction of a substance's molecular vibrations with laser light. While Raman imaging can provide a unique view of samples such as residual stress within silicon devices, chemical degradation, material aging, and sample heterogeneity, the Raman scattering process is often weak and thus requires very sensitive collection optics and detectors. Many commercial instruments (including ones owned here at Sandia National Laboratories) generate Raman images by raster scanning a point focused laser beam across a sample--a process which can expose a sample to extreme levels of laser light and requires lengthy acquisition times. Our previous research efforts have led to the development of a state-of-the-art two-dimensional hyperspectral imager for fluorescence imaging applications such as microarray scanning. This report details the design, integration, and characterization of a line-scan Raman imaging module added to this efficient hyperspectral fluorescence microscope. The original hyperspectral fluorescence instrument serves as the framework for excitation and sample manipulation for the Raman imaging system, while a more appropriate axial transmissive Raman imaging spectrometer and detector are utilized for collection of the Raman scatter. The result is a unique and flexible dual-modality fluorescence and Raman imaging system capable of high-speed imaging at high spatial and spectral resolutions. Care was taken throughout the design and integration process not to hinder any of the fluorescence imaging capabilities. For example, an operator can switch between the fluorescence and Raman modalities without need for extensive optical realignment. The instrument performance has been characterized and sample data is presented.

  17. Integrated paleontological data base and image library

    SciTech Connect

    Goodman, D.K. ); Becker, R.C. ); Van Couvering, J. ); Ford, L.N. Jr. ); Albert, N.R. )

    1991-03-01

    MICROBASE (MICROpaleontology data BASE) is an integrated data base and image retrieval system designed to increase the efficiency and precision with which paleontologists access and interpret paleontological and biostratigraphic data. The project is funded by a consortium of oil companies and coordinated by the American Museum of Natural History with assistance from the American Association of Stratigraphic Palynologists. MICROBASE is a PC-based MS DOS-compatible system operating under Microsoft Windows 3.0 that takes advantage of the latest developments in both analog (video) and digital technology. Images are captured using a video camera mounted on a microscope or using a high-resolution scanner for photographic source material. The image is saved either as a digital file or as an analog 'frame' on a Panasonic optical disk recorder (OMDR). The OMDR can store 108,000 images on one 12-in disk with a retrieval and display time of less than 0.15 second. Microfossil data (nomenclature, synonomy, descriptions, stratigraphic distribution, etc.) are stored as relational tables in an ORACLE DBMS (PALeontological CATalog, or PALCAT), and these textural data are linked to multiple images for each taxon. MICROBASE is the first integrated and widely supported system to electronically archive paleontological data, regardless of fossil group. It provides rapid, easy access to paleontological data, resulting in standardized taxonomy, more efficient identification procedures, substantially reduced learning curves for persons unfamiliar with particular groups, and more effective retention of the cumulative expertise of experienced paleontologists. The Ellis and Messina Catalog of Foraminifera is the first paleontological catalog available on the MICROBASE system.

  18. Design of an integrated aerial image sensor

    NASA Astrophysics Data System (ADS)

    Xue, Jing; Spanos, Costas J.

    2005-05-01

    The subject of this paper is a novel integrated aerial image sensor (IAIS) system suitable for integration within the surface of an autonomous test wafer. The IAIS could be used as a lithography processing monitor, affording a "wafer's eye view" of the process, and therefore facilitating advanced process control and diagnostics without integrating (and dedicating) the sensor to the processing equipment. The IAIS is composed of an aperture mask and an array of photo-detectors. In order to retrieve nanometer scale resolution of the aerial image with a practical photo-detector pixel size, we propose a design of an aperture mask involving a series of spatial phase "moving" aperture groups. We demonstrate a design example aimed at the 65nm technology node through TEMPEST simulation. The optimized, key design parameters include an aperture width in the range of 30nm, aperture thickness in the range of 70nm, and offer a spatial resolution of about 5nm, all with comfortable fabrication tolerances. Our preliminary simulation work indicates the possibility of the IAIS being applied to the immersion lithography. A bench-top far-field experiment verifies that our approach of the spatial frequency down-shift through forming large Moire patterns is feasible.

  19. Molecular Imaging of Myocardial Injury: A Magnetofluorescent Approach

    PubMed Central

    Sosnovik, David E.

    2009-01-01

    The role of molecular imaging in enhancing the understanding of myocardial injury and repair is rapidly expanding. Moreover, in recent years magnetic resonance and fluorescence-based approaches have been added to the molecular imaging armamentarium and have been used to image selected molecular and cellular targets in the myocardium. Apoptosis, necrosis, macrophage infiltration, myeloperoxidase activity, cathepsin activity, and type 1 collagen have all been imaged in vivo with a magnetofluorescent (MRI and/or fluorescence) approach. This review highlights the potential of these and other magnetofluorescent agents, with particular focus on their role in ischemic heart disease. PMID:20090858

  20. Molecular imaging: spawning a new melting-pot for biomedical imaging

    PubMed Central

    Abdullah, BJJ

    2006-01-01

    Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas. PMID:21614327

  1. Image analysis by integration of disparate information

    NASA Technical Reports Server (NTRS)

    Lemoigne, Jacqueline

    1993-01-01

    Image analysis often starts with some preliminary segmentation which provides a representation of the scene needed for further interpretation. Segmentation can be performed in several ways, which are categorized as pixel based, edge-based, and region-based. Each of these approaches are affected differently by various factors, and the final result may be improved by integrating several or all of these methods, thus taking advantage of their complementary nature. In this paper, we propose an approach that integrates pixel-based and edge-based results by utilizing an iterative relaxation technique. This approach has been implemented on a massively parallel computer and tested on some remotely sensed imagery from the Landsat-Thematic Mapper (TM) sensor.

  2. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Jerzy Bernholc

    2011-02-03

    will some day reach a miniaturization limit, forcing designers of Si-based electronics to pursue increased performance by other means. Any other alternative approach would have the unenviable task of matching the ability of Si technology to pack more than a billion interconnected and addressable devices on a chip the size of a thumbnail. Nevertheless, the prospects of developing alternative approaches to fabricate electronic devices have spurred an ever-increasing pace of fundamental research. One of the promising possibilities is molecular electronics (ME), self-assembled molecular-based electronic systems composed of single-molecule devices in ultra dense, ultra fast molecular-sized components. This project focused on developing accurate, reliable theoretical modeling capabilities for describing molecular electronics devices. The participants in the project are given in Table 1. The primary outcomes of this fundamental computational science grant are publications in the open scientific literature. As listed below, 62 papers have been published from this project. In addition, the research has also been the subject of more than 100 invited talks at conferences, including several plenary or keynote lectures. Many of the goals of the original proposal were completed. Specifically, the multi-disciplinary group developed a unique set of capabilities and tools for investigating electron transport in fabricated and self-assembled nanostructures at multiple length and time scales.

  3. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Weinan E

    2012-03-29

    The main bottleneck in modeling transport in molecular devices is to develop the correct formulation of the problem and efficient algorithms for analyzing the electronic structure and dynamics using, for example, the time-dependent density functional theory. We have divided this task into several steps. The first step is to developing the right mathematical formulation and numerical algorithms for analyzing the electronic structure using density functional theory. The second step is to study time-dependent density functional theory, particularly the far-field boundary conditions. The third step is to study electronic transport in molecular devices. We are now at the end of the first step. Under DOE support, we have made subtantial progress in developing linear scaling and sub-linear scaling algorithms for electronic structure analysis. Although there has been a huge amount of effort in the past on developing linear scaling algorithms, most of the algorithms developed suffer from the lack of robustness and controllable accuracy. We have made the following progress: (1) We have analyzed thoroughly the localization properties of the wave-functions. We have developed a clear understanding of the physical as well as mathematical origin of the decay properties. One important conclusion is that even for metals, one can choose wavefunctions that decay faster than any algebraic power. (2) We have developed algorithms that make use of these localization properties. Our algorithms are based on non-orthogonal formulations of the density functional theory. Our key contribution is to add a localization step into the algorithm. The addition of this localization step makes the algorithm quite robust and much more accurate. Moreover, we can control the accuracy of these algorithms by changing the numerical parameters. (3) We have considerably improved the Fermi operator expansion (FOE) approach. Through pole expansion, we have developed the optimal scaling FOE algorithm.

  4. PETglove: a new technology for portable molecular imaging

    NASA Astrophysics Data System (ADS)

    Wong, Kenneth H.; Gruionu, Lucian G.; Cheng, Patrick; Abshire, Pamela; Saveliev, Valeri; Mun, Seong K.; Cleary, Kevin; Weinberg, Irving N.

    2007-03-01

    PET (Positron Emission Tomography) scanning has become a dominant force in oncology care because of its ability to identify regions of abnormal function. The current generation of PET scanners is focused on whole-body imaging, and does not address aspects that might be required by surgeons or other practitioners interested in the function of particular body parts. We are therefore developing and testing a new class of hand-operated molecular imaging scanners designed for use with physical examinations and intraoperative visualization. These devices integrate several technological advances, including (1) nanotechnology-based quantum photodetectors for high performance at low light levels, (2) continuous position tracking of the detectors so that they form a larger 'virtual detector', and (3) novel reconstruction algorithms that do not depend on a circular or ring geometry. The first incarnations of this device will be in the form of a glove with finger-mounted detectors or in a "sash" of detectors that can be draped over the patient. Potential applications include image-guided biopsy, surgical resection of tumors, assessment of inflammatory conditions, and early cancer detection. Our first prototype is in development now along with a clinical protocol for pilot testing.

  5. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    PubMed

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

  6. Integrated IVUS-OCT Imaging for Atherosclerotic Plaque Characterization

    PubMed Central

    Li, Xiang; Li, Jiawen; Jing, Joe; Ma, Teng; Liang, Shanshan; Zhang, Jun; Mohar, Dilbahar; Raney, Aidan; Mahon, Sari; Brenner, Matthew; Patel, Pranav; Shung, K. Kirk; Zhou, Qifa; Chen, Zhongping

    2014-01-01

    For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. Ex vivo and in vivo experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality. PMID:24771992

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

    PubMed

    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

  8. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  9. New Approaches to Molecular Imaging of Multiple Myeloma.

    PubMed

    Vij, Ravi; Fowler, Kathryn J; Shokeen, Monica

    2016-01-01

    Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal bone marrow plasma cells characterized by destructive bone lesions and is fatal in most patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Progressive biomedical imaging technologies such as low-dose CT, molecularly targeted PET, MRI, and the functional-anatomic hybrid versions (PET/CT and PET/MRI) provide incremental advancements in imaging MM. Imaging with PET and MRI using molecularly targeted probes is a promising precision medicine platform that might successfully address the clinical ambiguities of myeloma spectrum diseases. The intent of this focus article is to provide a concise review of the present status and promising developments on the horizon, such as the new molecular imaging biomarkers under investigation that can either complement or potentially supersede existing standards. PMID:26541780

  10. Molecular imaging in the framework of personalized cancer medicine.

    PubMed

    Belkić, Dzevad; Belkić, Karen

    2013-11-01

    With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers. PMID:24511645

  11. Image-guided surgery using multimodality strategy and molecular probes.

    PubMed

    Xi, Lei; Jiang, Hubei

    2016-01-01

    The ultimate goal of cancer surgery is to maximize the excision of tumorous tissue with minimal damage to the collateral normal tissues, reduce the postoperative recurrence, and improve the survival rate of patients. In order to locate tumor lesions, highlight tumor margins, visualize residual disease in the surgical wound, and map potential lymph node metastasis, various imaging techniques and molecular probes have been investigated to assist surgeons to perform more complete tumor resection. Combining imaging techniques with molecular probes is particularly promising as a new approach for image-guided surgery. Considering inherent limitations of different imaging techniques and insufficient sensitivity of nonspecific molecular probes, image-guided surgery with multimodality strategy and specific molecular probes appears to be an optimal choice. In this article, we briefly describe typical imaging techniques and molecular probes followed by a focused review on the current progress of multimodal image-guided surgery with specific molecular navigation. We also discuss optimal strategy that covers all stages of image-guided surgery including preoperative scanning of tumors, intraoperative inspection of surgical bed and postoperative care of patients. PMID:26053199

  12. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  13. Quantum tunneling splittings from path-integral molecular dynamics.

    PubMed

    Mátyus, Edit; Wales, David J; Althorpe, Stuart C

    2016-03-21

    We illustrate how path-integral molecular dynamics can be used to calculate ground-state tunnelling splittings in molecules or clusters. The method obtains the splittings from ratios of density matrix elements between the degenerate wells connected by the tunnelling. We propose a simple thermodynamic integration scheme for evaluating these elements. Numerical tests on fully dimensional malonaldehyde yield tunnelling splittings in good overall agreement with the results of diffusion Monte Carlo calculations. PMID:27004863

  14. Molecular imaging and personalized medicine: an uncertain future.

    PubMed

    Nunn, Adrian D

    2007-12-01

    The Food and Drug Administration has described their view of the role that imaging will play in the approval, and perhaps postapproval, use of new therapeutic drugs. The therapeutic drug industry and regulatory authorities have turned to imaging to help them achieve better efficiency and efficacy. We must extend this initiative by demonstrating that molecular imaging can also improve the efficiency and efficacy of routine treatment with these same drugs. The role of molecular imaging in personalized medicine, using targeted drugs in oncology, is very attractive because of the regional information that it provides (in many cases, with a functional or dynamic component), which cannot be provided by in vitro methods ("regional proteomics"). There is great potential for molecular imaging to play a major role in selecting appropriate patients and providing early proof of response, which is critical to addressing the conflict between the high price of treatment and limited reimbursement budgets. This is a new venture in both molecular imaging and targeted drugs. However, there are various regulatory, financial, and practical barriers that must be overcome to achieve this aim, in addition to the normal scientific challenges of drug discovery. There is an urgent need to reduce the cost (i.e., time and money) of developing imaging agents for routine clinical use. The mismatch between the current regulations and personalized medicine includes molecular imaging and requires the engagement of the regulatory authorities to correct. Therapeutic companies must be engaged early in the development of new targeted drugs and molecular imaging agents to improve the fit between the two drug types. Clinical trials must be performed to generate data that not only shows the efficacy of imaging plus therapy in a medical sense, but also in a financial sense. Molecular imaging must be accepted as not just good science but also as central to routine patient management in the personalized

  15. Image engine: an integrated multimedia clinical information system.

    PubMed

    Lowe, H J; Buchanan, B G; Cooper, G F; Kaplan, B; Vries, J K

    1995-01-01

    Image Engine is a microcomputer-based system for the integration, storage, retrieval, and sharing of digitized clinical images. The system seeks to address the problem of integrating a wide range of clinically important images with the text-based electronic patient record. Rather than create a single, integrated database system for all clinical data, we are developing a separate image database system that creates real-time, dynamic links to other network-based clinical databases. To the user, this system will present an integrated multimedia representation of the patient record, providing access to both the image and text-based data required for effective clinical decision making. PMID:8591216

  16. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  17. Translational Applications of Molecular Imaging and Radionuclide Therapy

    SciTech Connect

    Welch, Michael J.; Eckelman, William C.; Vera, David

    2005-06-17

    Molecular imaging is becoming a larger part of imaging research and practice. The Office of Biological and Environmental Research of the Department of Energy funds a significant number of researchers in this area. The proposal is to partially fund a workshop to inform scientists working in nuclear medicine and nuclear medicine practitioners of the recent advances of molecular imaging in nuclear medicine as well as other imaging modalities. A limited number of topics related to radionuclide therapy will also be discussed. The proposal is to request partial funds for the workshop entitled “Translational Applications of Molecular Imaging and Radionuclide Therapy” to be held prior to the Society of Nuclear Medicine Annual Meeting in Toronto, Canada in June 2005. The meeting will be held on June 17-18. This will allow scientists interested in all aspects of nuclear medicine imaging to attend. The chair of the organizing group is Dr. Michael J. Welch. The organizing committee consists of Dr. Welch, Dr. William C. Eckelman and Dr. David Vera. The goal is to invite speakers to discuss the most recent advances of modern molecular imaging and therapy. Speakers will present advances made in in vivo tagging imaging assays, technical aspects of small animal imaging, in vivo imaging and bench to bedside translational study – the role of a diagnostic scan on therapy selection. This latter topic will include discussions on α therapy and new approaches to dosimetry. Several of these topics are those funded by the Department of Energy Office of Biological and Environmental Research.

  18. Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

    SciTech Connect

    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.

  19. Molecular Imaging of Angiogenesis and Vascular Remodeling in Cardiovascular Pathology

    PubMed Central

    Golestani, Reza; Jung, Jae-Joon; Sadeghi, Mehran M.

    2016-01-01

    Angiogenesis and vascular remodeling are involved in a wide array of cardiovascular diseases, from myocardial ischemia and peripheral arterial disease, to atherosclerosis and aortic aneurysm. Molecular imaging techniques to detect and quantify key molecular and cellular players in angiogenesis and vascular remodeling (e.g., vascular endothelial growth factor and its receptors, αvβ3 integrin, and matrix metalloproteinases) can advance vascular biology research and serve as clinical tools for early diagnosis, risk stratification, and selection of patients who would benefit most from therapeutic interventions. To target these key mediators, a number of molecular imaging techniques have been developed and evaluated in animal models of angiogenesis and vascular remodeling. This review of the state of the art molecular imaging of angiogenesis and vascular (and valvular) remodeling, will focus mostly on nuclear imaging techniques (positron emission tomography and single photon emission tomography) that offer high potential for clinical translation. PMID:27275836

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

    PubMed Central

    Velikyan, Irina

    2012-01-01

    This theme issue presents current achievements in the development of radioactive agents, pre-clinical and clinical molecular imaging, and radiotherapy in the context of theranostics in the field of oncology. PMID:22768022

  1. Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis

    NASA Astrophysics Data System (ADS)

    Levin, Galit; Shirvan, Anat; Grimberg, Hagit; Reshef, Ayelet; Yogev-Falach, Merav; Cohen, Avi; Ziv, Ilan

    2009-09-01

    Chemotherapy-induced enteropathy (CIE) is one of the most serious complications of anticancer therapy, and tools for its early detection and monitoring are highly needed. We report on a novel fluorescence method for detection of CIE, based on molecular imaging of the related apoptotic process. The method comprises systemic intravenous administration of the ApoSense fluorescent biomarker (N,N'-didansyl-L-cystine DDC) in vivo and subsequent fluorescence imaging of the intestinal mucosa. In the reported proof-of-concept studies, mice were treated with either taxol+cyclophosphamide or doxil. DDC was administered in vivo at various time points after drug administration, and tracer uptake by ileum tissue was subsequently evaluated by ex vivo fluorescent microscopy. Chemotherapy caused marked and selective uptake of DDC in ileal epithelial cells, in correlation with other hallmarks of apoptosis (i.e., DNA fragmentation and Annexin-V binding). Induction of DDC uptake occurred early after chemotherapy, and its temporal profile was parallel to that of the apoptotic process, as assessed histologically. DDC may therefore serve as a useful tool for detection of CIE. Future potential integration of this method with fluorescent endoscopic techniques, or development of radio-labeled derivatives of DDC for emission tomography, may advance early diagnosis and monitoring of this severe adverse effect of chemotherapy.

  2. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  3. Molecular Imaging in Tumor Angiogenesis and Relevant Drug Research

    PubMed Central

    Ma, Xibo; Tian, Jie; Yang, Xin; Qin, Chenghu

    2011-01-01

    Molecular imaging, including fluorescence imaging (FMI), bioluminescence imaging (BLI), positron emission tomography (PET), single-photon emission-computed tomography (SPECT), and computed tomography (CT), has a pivotal role in the process of tumor and relevant drug research. CT, especially Micro-CT, can provide the anatomic information for a region of interest (ROI); PET and SPECT can provide functional information for the ROI. BLI and FMI can provide optical information for an ROI. Tumor angiogenesis and relevant drug development is a lengthy, high-risk, and costly process, in which a novel drug needs about 10–15 years of testing to obtain Federal Drug Association (FDA) approval. Molecular imaging can enhance the development process by understanding the tumor mechanisms and drug activity. In this paper, we focus on tumor angiogenesis, and we review the characteristics of molecular imaging modalities and their applications in tumor angiogenesis and relevant drug research. PMID:21808639

  4. Nanobody: The “Magic Bullet” for Molecular Imaging?

    PubMed Central

    Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

    2014-01-01

    Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases. PMID:24578722

  5. Molecular Imaging-Guided Interventional Hyperthermia in Treatment of Breast Cancer

    PubMed Central

    Zhou, Yurong; Sun, Jihong; Yang, Xiaoming

    2015-01-01

    Breast cancer is the most frequent malignancy in women worldwide. Although it is commonly treated via chemotherapy, responses vary among its subtypes, some of which are relatively insensitive to chemotherapeutic drugs. Recent studies have shown that hyperthermia can enhance the effects of chemotherapy in patients with refractory breast cancer or without surgical indications. Recent advances in molecular imaging may not only improve early diagnosis but may also facilitate the development and response assessment of targeted therapies. Combining advanced techniques such as molecular imaging and hyperthermia-integrated chemotherapy should open new avenues for effective management of breast cancer. PMID:26491673

  6. MRI Reporter Genes for Noninvasive Molecular Imaging.

    PubMed

    Yang, Caixia; Tian, Rui; Liu, Ting; Liu, Gang

    2016-01-01

    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. PMID:27213309

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Molecular Body Imaging: MR Imaging, CT, and US. Part I. Principles

    PubMed Central

    Kircher, Moritz F.

    2012-01-01

    Molecular imaging, generally defined as noninvasive imaging of cellular and subcellular events, has gained tremendous depth and breadth as a research and clinical discipline in recent years. The coalescence of major advances in engineering, molecular biology, chemistry, immunology, and genetics has fueled multi- and interdisciplinary innovations with the goal of driving clinical noninvasive imaging strategies that will ultimately allow disease identification, risk stratification, and monitoring of therapy effects with unparalleled sensitivity and specificity. Techniques that allow imaging of molecular and cellular events facilitate and go hand in hand with the development of molecular therapies, offering promise for successfully combining imaging with therapy. While traditionally nuclear medicine imaging techniques, in particular positron emission tomography (PET), PET combined with computed tomography (CT), and single photon emission computed tomography, have been the molecular imaging methods most familiar to clinicians, great advances have recently been made in developing imaging techniques that utilize magnetic resonance (MR), optical, CT, and ultrasonographic (US) imaging. In the first part of this review series, we present an overview of the principles of MR imaging-, CT-, and US-based molecular imaging strategies. © RSNA, 2012 PMID:22623690

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

    PubMed

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

    2007-06-01

    Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information. PMID:17084109

  10. Image force microscopy of molecular resonance: A microscope principle

    PubMed Central

    Rajapaksa, I.; Uenal, K.; Wickramasinghe, H. Kumar

    2010-01-01

    We demonstrate a technique in microscopy which extends the domain of atomic force microscopy to optical spectroscopy at the nanometer scale. We show that molecular resonance of feature sizes down to the single molecular level can be detected and imaged purely by mechanical detection of the force gradient between the interaction of the optically driven molecular dipole and its mirror image in a platinum coated scanning probe tip. This microscopy and spectroscopy technique is extendable to frequencies ranging from radio to infrared and the ultraviolet. PMID:20859536

  11. Human gesture recognition using three-dimensional integral imaging.

    PubMed

    Javier Traver, V; Latorre-Carmona, Pedro; Salvador-Balaguer, Eva; Pla, Filiberto; Javidi, Bahram

    2014-10-01

    Three-dimensional (3D) integral imaging allows one to reconstruct a 3D scene, including range information, and provides sectional refocused imaging of 3D objects at different ranges. This paper explores the potential use of 3D passive sensing integral imaging for human gesture recognition tasks from sequences of reconstructed 3D video scenes. As a preliminary testbed, the 3D integral imaging sensing is implemented using an array of cameras with the appropriate algorithms for 3D scene reconstruction. Recognition experiments are performed by acquiring 3D video scenes of multiple hand gestures performed by ten people. We analyze the capability and performance of gesture recognition using 3D integral imaging representations at given distances and compare its performance with the use of standard two-dimensional (2D) single-camera videos. To the best of our knowledge, this is the first report on using 3D integral imaging for human gesture recognition. PMID:25401260

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

    PubMed Central

    Huang, Hsuan-Ming; Shih, Yi-Yu

    2014-01-01

    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. PMID:24738056

  13. Molecular imaging in atherosclerosis, thrombosis and vascular inflammation

    PubMed Central

    Choudhury, Robin P.; Fisher, Edward A.

    2009-01-01

    Appreciation of the molecular and cellular processes of atherosclerosis, thrombosis and vascular inflammation has identified new targets for imaging. The common goals of molecular imaging approaches are to accelerate and refine diagnosis, provide insights that reveal disease diversity, guide specific therapies and monitor the effects of those therapies. Here we undertake a comparative analysis of imaging modalities that have been used in this disease area. We consider the elements of contrast agents, emphasizing how an understanding of the biology of atherosclerosis and its complications can inform optimal design. We address the potential and limitations of current contrast approaches in respect of translation to clinically usable agents and speculate on future applications. PMID:19213945

  14. On the potential for molecular imaging with Cerenkov luminescence

    PubMed Central

    Lewis, Matthew A.; Kodibagkar, Vikram D.; Öz, Orhan K.; Mason, Ralph P.

    2011-01-01

    Recent observation of optical luminescence due to beta decay from suitable radiotracers has led to the possible development of new preclinical optical imaging methods. The generation of photons that can be detected using instrumentation optimized for bioluminescence imaging has been putatively associated with the Cerenkov effect. We describe the simultaneous utilization of fluorescence reporters to convert the Cerenkov luminescence to longer wavelengths for better tissue penetration and also for modulating the luminescence spectrum for potential molecular imaging strategies. PMID:21124555

  15. Quantum dot imaging platform for single-cell molecular profiling

    NASA Astrophysics Data System (ADS)

    Zrazhevskiy, Pavel; Gao, Xiaohu

    2013-03-01

    Study of normal cell physiology and disease pathogenesis heavily relies on untangling the complexity of intracellular molecular mechanisms and pathways. To achieve this goal, comprehensive molecular profiling of individual cells within the context of microenvironment is required. Here we report the development of a multicolour multicycle in situ imaging technology capable of creating detailed quantitative molecular profiles for individual cells at the resolution of optical imaging. A library of stoichiometric fluorescent probes is prepared by linking target-specific antibodies to a universal quantum dot-based platform via protein A in a quick and simple procedure. Surprisingly, despite the potential for multivalent binding between protein A and antibody and the intermediate affinity of this non-covalent bond, fully assembled probes do not aggregate or exchange antibodies, facilitating highly multiplexed parallel staining. This single-cell molecular profiling technology is expected to open new opportunities in systems biology, gene expression studies, signalling pathway analysis and molecular diagnostics.

  16. Molecular Optical Coherence Tomography Contrast Enhancement and Imaging

    NASA Astrophysics Data System (ADS)

    Oldenburg, Amy L.; Applegate, Brian E.; Tucker-Schwartz, Jason M.; Skala, Melissa C.; Kim, Jongsik; Boppart, Stephen A.

    Histochemistry began as early as the nineteenth century, with the development of synthetic dyes that provided spatially mapped chemical contrast in tissue [1]. Stains such as hematoxylin and eosin, which contrast cellular nuclei and cytoplasm, greatly aid in the interpretation of microscopy images. An analogous development is currently taking place in biomedical imaging, whereby techniques adapted for MRI, CT, and PET now provide in vivo molecular imaging over the entire human body, aiding in both fundamental research discovery and in clinical diagnosis and treatment monitoring. Because OCT offers a unique spatial scale that is intermediate between microscopy and whole-body biomedical imaging, molecular contrast OCT (MCOCT) also has great potential for providing new insight into in vivo molecular processes. The strength of MCOCT lies in its ability to isolate signals from a molecule or contrast agent from the tissue scattering background over large scan areas at depths greater than traditional microscopy techniques while maintaining high resolution.

  17. Nanomedicine strategies for molecular targets with MRI and optical imaging

    PubMed Central

    Pan, Dipanjan; Caruthers, Shelton D; Chen, Junjie; Winter, Patrick M; SenPan, Angana; Schmieder, Anne H; Wickline, Samuel A

    2010-01-01

    The science of ‘theranostics’ plays a crucial role in personalized medicine, which represents the future of patient management. Over the last decade an increasing research effort has focused on the development of nanoparticle-based molecular-imaging and drug-delivery approaches, emerging as a multidisciplinary field that shows promise in understanding the components, processes, dynamics and therapies of a disease at a molecular level. The potential of nanometer-sized agents for early detection, diagnosis and personalized treatment of diseases is extraordinary. They have found applications in almost all clinically relevant biomedical imaging modality. In this review, a number of these approaches will be presented with a particular emphasis on MRI and optical imaging-based techniques. We have discussed both established molecular-imaging approaches and recently developed innovative strategies, highlighting the seminal studies and a number of successful examples of theranostic nanomedicine, especially in the areas of cardiovascular and cancer therapy. PMID:20485473

  18. Imaging in the era of molecular oncology

    PubMed Central

    Weissleder, Ralph; Pittet, Mikael J.

    2009-01-01

    New technologies for imaging molecules, particularly optical technologies, are increasingly being used to understand the complexity, diversity and in vivo behaviour of cancers. ‘Omic’ approaches are providing comprehensive ‘snapshots’ of biological indicators, or biomarkers, of cancer, but imaging can take this information a step further, showing the activity of these markers in vivo and how their location changes over time. Advances in experimental and clinical imaging are likely to improve how cancer is understood at a systems level and, ultimately, should enable doctors not only to locate tumours but also to assess the activity of the biological processes within these tumours and to provide ‘on the spot’ treatment. PMID:18385732

  19. The Integration of 3-D Cell-Printing and Mesoscopic Fluorescence Molecular Tomography of Vascular Constructs within Thick Hydrogel Scaffolds

    PubMed Central

    Zhao, Lingling; Lee, Vivian K.; Yoo, Seung-Schik; Dai, Guohao; Intes, Xavier

    2012-01-01

    Developing methods that provide adequate vascular perfusion is an important step toward engineering large functional tissues. Meanwhile, an imaging modality to assess the three-dimensional (3-D) structures and functions of the vascular channels is lacking for thick matrices (>2~3mm). Herein, we report on an original approach to construct and image 3-D dynamically perfused vascular structures in thick hydrogel scaffolds. In this work, we integrated a robotic 3-D cell-printing technology with a mesoscopic fluorescence molecular tomography imaging system, and demonstrated the capability of the platform to construct perfused collagen scaffolds with endothelial lining and to image both the fluid flow and fluorescent-labeled living endothelial cells at high-frame rates, with high sensitivity and accuracy. These results establish the potential of integrating both 3-D cell-printing and fluorescence mesoscopic imaging for functional and molecular studies in complex tissue engineered tissues. PMID:22531221

  20. Advances of Molecular Imaging in Epilepsy.

    PubMed

    Galovic, Marian; Koepp, Matthias

    2016-06-01

    Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the location of the epileptic focus. PET studies have examined the role of opioids, cannabinoids, acetylcholine, and dopamine in modulating neuronal hyperexcitability and seizure termination. In vivo analyses of drug transporters, e.g., P-glycoprotein, have increased our understanding of pharmacoresistance that could inform new therapeutic strategies. Finally, PET experiments targeting neuroinflammation and glutamate receptors might guide the development of novel biomarkers of epileptogenesis. PMID:27113252

  1. How have developments in molecular imaging techniques furthered schizophrenia research?

    PubMed Central

    Thompson, Judy L; Urban, Nina; Abi-Dargham, Anissa

    2010-01-01

    Molecular imaging techniques have led to significant advances in understanding the pathophysiology of schizophrenia and contributed to knowledge regarding potential mechanisms of action of the drugs used to treat this illness. The aim of this article is to provide a review of the major findings related to the application of molecular imaging techniques that have furthered schizophrenia research. This article focuses specifically on neuroreceptor imaging studies with PET and SPECT. After providing a brief overview of neuroreceptor imaging methodology, we consider relevant findings from studies of receptor availability, and dopamine synthesis and release. Results are discussed in the context of current hypotheses regarding neurochemical alterations in the illness. We then selectively review pharmacological occupancy studies and the role of neuroreceptor imaging in drug development for schizophrenia. PMID:21243081

  2. Advances in multimodality molecular imaging of bone structure and function

    PubMed Central

    Lambers, Floor M; Kuhn, Gisela; Müller, Ralph

    2012-01-01

    The skeleton is important to the body as a source of minerals and blood cells and provides a structural framework for strength, mobility and the protection of organs. Bone diseases and disorders can have deteriorating effects on the skeleton, but the biological processes underlying anatomical changes in bone diseases occurring in vivo are not well understood, mostly due to the lack of appropriate analysis techniques. Therefore, there is ongoing research in the development of novel in vivo imaging techniques and molecular markers that might help to gain more knowledge of these pathological pathways in animal models and patients. This perspective provides an overview of the latest developments in molecular imaging applied to bone. It emphasizes that multimodality imaging, the combination of multiple imaging techniques encompassing different image modalities, enhances the interpretability of data, and is imperative for the understanding of the biological processes and the associated changes in bone structure and function relationships in vivo. PMID:27127622

  3. jAMVLE, A new integrated molecular visualization learning environment*.

    PubMed

    Bottomley, Steven; Chandler, David; Morgan, Eleanor; Helmerhorst, Erik

    2006-09-01

    A new computer-based molecular visualization tool has been developed for teaching, and learning, molecular structure. This java-based jmol Amalgamated Molecular Visualization Learning Environment (jAMVLE) is platform-independent, integrated, and interactive. It has an overall graphical user interface that is intuitive and easy to use. The application can be downloaded free from the internet at wabri.org.au/jamvle. A cohort of 28 third year undergraduate molecular biotechnology degree students evaluated the new application through an essay-style project. These were analyzed to identify themes expressed by students in the content of their evaluations. Most students were positive about the new jAMVLE learning environment, and five major benefits emerged from the analysis. In particular, the students perceived that jAMVLE has an appealing interface, is interactive, provides a useful integrated environment, is user friendly, and is an excellent learning tool. Overall, students found that the jAMVLE application stimulated their interest, was a more active learning environment, provided better guidance, and made learning fun. PMID:21638712

  4. New strategy for monitoring targeted therapy: molecular imaging

    PubMed Central

    Teng, Fei-Fei; Meng, Xue; Sun, Xin-Dong; Yu, Jin-Ming

    2013-01-01

    Targeted therapy is becoming an increasingly important component in the treatment of cancer. How to accurately monitor targeted therapy has been crucial in clinical practice. The traditional approach to monitor treatment through imaging has relied on assessing the change of tumor size by refined World Health Organization criteria, or more recently, by the Response Evaluation Criteria in Solid Tumors. However, these criteria, which are based on the change of tumor size, show some limitations for evaluating targeted therapy. Currently, genetic alterations are identified with prognostic as well as predictive potential concerning the use of molecularly targeted drugs. Conversely, considering the limitations of invasiveness and the issue of expression heterogeneity, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively, and has been a particularly attractive tool for monitoring treatment in clinical cancer practice. This review focuses on the applications of different kinds of molecular imaging including positron emission tomography-, magnetic resonance imaging-, ultrasonography-, and computed tomography-based imaging strategies on monitoring targeted therapy. In addition, the key challenges of molecular imaging are addressed to successfully translate these promising techniques in the future. PMID:24124361

  5. Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques

    PubMed Central

    2014-01-01

    Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ3 integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein. PMID:25099015

  6. Fluorescent Molecular Imaging and Dosimetry Tools in Photodynamic Therapy

    PubMed Central

    Pogue, Brian W.; Samkoe, Kimberley S.; Gibbs-Strauss, Summer L.; Davis, Scott C.

    2013-01-01

    Measurement of fluorescence and phosphorescence in vivo is readily used to quantify the concentration of specific species that are relevant to photodynamic therapy. However, the tools to make the data quantitatively accurate vary considerably between different applications. Sampling of the signal can be done with point samples, such as specialized fiber probes or from bulk regions with either imaging or sampling, and then in broad region image-guided manner. Each of these methods is described below, the application to imaging photosensitizer uptake is discussed, and developing methods to image molecular responses to therapy are outlined. PMID:20552350

  7. Emerging Applications of Conjugated Polymers in Molecular Imaging

    PubMed Central

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

    2013-01-01

    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. PMID:23860904

  8. Molecular imaging by single-photon emission

    NASA Astrophysics Data System (ADS)

    Cusanno, F.; Accorsi, R.; Cinti, M. N.; Colilli, S.; Fortuna, A.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lanza, R. C.; Loizzo, A.; Lucentini, M.; Pani, R.; Pellegrini, R.; Santavenere, F.; Scopinaro, F.

    2004-07-01

    In vivo imaging of pharmaceuticals labeled with radionuclides has proven to be a powerful tool in human subjects. The same imaging methods have often been applied to small animal but usually only within the nuclear medicine (NM) community, and usually only to evaluate the efficacy of new radiopharmaceuticals. We have built a compact mini gamma camera, a pixellated array of NaI(Tl) crystals coupled to 3'' R2486 Hamamatsu Position Sensitive PMT; in combination with a pinhole collimator, which allows for high resolution in vivo SPECT imaging. Calculations show that reasonable counting rates are possible. The system has been tested and preliminary measurements on mice have been done. The performances of the camera are in the expectations. Improvements will be done both on the collimation technique and on the detector. Simulations have been performed to study a coded aperture collimator. The results show that the efficiency can be greatly improved without sacrificing the spatial resolution. A dedicated mask has been designed and will be used soon.

  9. 3D augmented reality with integral imaging display

    NASA Astrophysics Data System (ADS)

    Shen, Xin; Hua, Hong; Javidi, Bahram

    2016-06-01

    In this paper, a three-dimensional (3D) integral imaging display for augmented reality is presented. By implementing the pseudoscopic-to-orthoscopic conversion method, elemental image arrays with different capturing parameters can be transferred into the identical format for 3D display. With the proposed merging algorithm, a new set of elemental images for augmented reality display is generated. The newly generated elemental images contain both the virtual objects and real world scene with desired depth information and transparency parameters. The experimental results indicate the feasibility of the proposed 3D augmented reality with integral imaging.

  10. A Novel Method of Line Detection using Image Integration Method

    NASA Astrophysics Data System (ADS)

    Lin, Daniel; Sun, Bo

    2015-03-01

    We developed a novel line detection algorithm based on image integration method. Hough Transformation uses spatial image gradient method to detect lines on an image. This is problematic because if the image has a region of high noise intensity, the gradient would point towards the noisy region . Denoising the noisy image requires an application of sophisticated noise reduction algorithm which increases computation complexity. Our algorithm can remedy this problem by averaging the pixels around the image region of interest. We were able to detect collagen fiber lines on an image produced by confocal microscope.

  11. Molecular imaging of breast cancer: present and future directions

    PubMed Central

    Alcantara, David; Leal, Manuel Pernia; García-Bocanegra, Irene; García-Martín, Maria L.

    2014-01-01

    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 tumor 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 tumor 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. PMID:25566530

  12. Molecular breast imaging using a dedicated high-performance instrument

    NASA Astrophysics Data System (ADS)

    O'Connor, Michael K.; Wagenaar, Douglas; Hruska, Carrie B.; Phillips, Stephen; Caravaglia, Gina; Rhodes, Deborah

    2006-08-01

    In women with radiographically dense breasts, the sensitivity of mammography is less than 50%. With the increase in the percent of women with dense breasts, it is important to look at alternative screening techniques for this population. This article reviews the strengths and weaknesses of current imaging techniques and focuses on recent developments in semiconductor-based gamma camera systems that offer significant improvements in image quality over that achievable with single-crystal sodium iodide systems. We have developed a technique known as Molecular Breast Imaging (MBI) using small field of view Cadmium Zinc Telluride (CZT) gamma cameras that permits the breast to be imaged in a similar manner to mammography, using light pain-free compression. Computer simulations and experimental studies have shown that use of low-energy high sensitivity collimation coupled with the excellent energy resolution and intrinsic spatial resolution of CZT detectors provides optimum image quality for the detection of small breast lesions. Preliminary clinical studies with a prototype dual-detector system have demonstrated that Molecular Breast Imaging has a sensitivity of ~90% for the detection of breast tumors less than 10 mm in diameter. By comparison, conventional scintimammography only achieves a sensitivity of 50% in the detection of lesions < 10 mm. Because Molecular Breast Imaging is not affected by breast density, this technique may offer an important adjunct to mammography in the evaluation of women with dense breast parenchyma.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Integrative molecular profiling of routine clinical prostate cancer specimens

    PubMed Central

    Grasso, C. S.; Cani, A. K.; Hovelson, D. H.; Quist, M. J.; Douville, N. J.; Yadati, V.; Amin, A. M.; Nelson, P. S.; Betz, B. L.; Liu, C-J.; Knudsen, K. E.; Cooney, K. A.; Feng, F. Y.; McDaniel, A. S.; Tomlins, S. A.

    2015-01-01

    Background Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. Patients and methods We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. Results We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. Conclusions Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized

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

    NASA Astrophysics Data System (ADS)

    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 < 3 mm depth. Unfortunately, patient 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.

  16. Integrated computational imaging system for enhanced polarimetric measurements

    NASA Astrophysics Data System (ADS)

    Haider, Shahid A.; Kazemzadeh, Farnoud; Clausi, David A.; Wong, Alexander

    2015-09-01

    Polarimetry is a common technique used in chemistry for solution characterization and analysis, giving insight into the molecular structure of a solution measured through the rotation of linearly polarized light. This rotation is characterized by the Boits law. Without large optical path lengths, or high concentrations of solution, these optical rotations are typically very small, requiring elaborate and costly apparatuses. To ensure that the rotation measurements are accurate, these devices usually perform complex optical procedures or time-averaged point measurements to ensure that any intensity variation seen is a product of optical rotation and not from inherent noise sources in the system, such as sensor or shot noise. Time averaging is a lengthy process and rarely utilizes all of the information available on the sensor. To this end, we have developed a novel integrated, miniature, computational imaging system that enhances polarimetric measurements by taking advantage of the full spot size observed on an array detector. This computational imaging system is capable of using a single acquisition at unity gain to enhance the polarimetric measurements using a probabilistic framework, which accounts for inherent noise and optical characteristics in the acquisition process, to take advantage of spatial intensity relations. This approach is faster than time-averaging methods and can better account for any measurement uncertainties. In preliminary experiments, this system has produced comparably consistent measurements across multiple trials with the same chemical solution than time averaging techniques.

  17. Imprints of Molecular Clouds in Radio Continuum Images

    NASA Astrophysics Data System (ADS)

    Yusef-Zadeh, F.

    2012-11-01

    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 path lengths 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 demonstrates an anti-correlation between the distributions of radio continuum and molecular line and dust emission. Radio dark clouds are identified in Green Bank Telescope maps and Very Large Array images taken with uniform sampling of uv coverage. The level at which the continuum flux is suppressed in these sources suggests that the depth of the molecular cloud is similar to the size of the continuum emission within a factor of two. These examples suggest that high-resolution, high-dynamic-range continuum images can be powerful probes of interacting molecular clouds with massive stars and supernova remnants in regions where the kinematic distance estimates are ambiguous as well as in the nuclei of active galaxies.

  18. Multimodality molecular imaging--from target description to clinical studies.

    PubMed

    Schober, O; Rahbar, K; Riemann, B

    2009-02-01

    This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations. PMID:19130054

  19. Multiphoton and photothermal imaging of molecular events in cancer

    NASA Astrophysics Data System (ADS)

    Skala, Melissa

    2010-10-01

    Optical techniques are attractive for monitoring disease processes in living tissues because they are relatively cheap, non-invasive and provide a wealth of functional information. Multiphoton microscopy (MPM) and Optical Coherence Tomography (OCT) are two types of three-dimensional optical imaging modalities that have demonstrated great utility in pre-clinical models of disease. These techniques are particularly useful for identifying metabolic and molecular biomarkers in cancer. These biomarkers can be used to identify the mechanisms of tumor growth, and to predict the response of a particular tumor to treatment. Specifically, MPM of the co-enzymes NADH and FAD was used to quantify metabolic changes associated with developing cancers in vivo. This imaging technique exploits intrinsic sources of tissue contrast and thus does not require contrast agents. Ongoing work combines this metabolic imaging technique with vascular imaging to provide a comprehensive picture of oxygen supply and demand with tumor therapy. Molecular signaling represents a third critical component in tumor physiology. To this end we have recently developed photothermal OCT, which combines coherent detection with laser-heated gold nanoparticles to achieve high-resolution molecular contrast at deeper depths than MPM. This multi-functional imaging platform will provide unprecedented insight into oxygen supply and demand, and molecular signaling in response to tumor growth and targeted cancer therapies in pre-clinical models.

  20. Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

    PubMed Central

    Shuhendler, Adam J.; Ye, Deju; Brewer, Kimberly D.; Bazalova-Carter, Magdalena; Lee, Kyung-Hyun; Kempen, Paul; Dane Wittrup, K.; Graves, Edward E.; Rutt, Brian; Rao, Jianghong

    2015-01-01

    Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring. PMID:26440059

  1. Recent Advances in Molecular, Multimodal and Theranostic Ultrasound Imaging

    PubMed Central

    Kiessling, Fabian; Fokong, Stanley; Bzyl, Jessica; Lederle, Wiltrud; Palmowski, Moritz; Lammers, Twan

    2014-01-01

    Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or hard shells. By conjugating antibodies to the microbubble (MB) surface, and by incorporating diagnostic agents, drugs or nucleic acids into or onto the MB shell, molecular, multimodal and theranostic MB can be generated. We here summarize recent advances in molecular, multimodal and theranostic US imaging, and introduce concepts how such advanced MB can be generated, applied and imaged. Examples are given for their use to image and treat oncological, cardiovascular and neurological diseases. Furthermore, we discuss for which therapeutic entities incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB destruction can increase their extravasation, penetration, internalization and efficacy. PMID:24316070

  2. Molecular imaging: a promising tool to monitor islet transplantation.

    PubMed

    Wang, Ping; Medarova, Zdravka; Moore, Anna

    2011-01-01

    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. PMID:22013504

  3. [Performance analysis and radiometric correction of novel molecular hyperspectral imaging system].

    PubMed

    Liu, Hong-Ying; Li, Qing-Li; Gu, Bin; Wang, Yi-Ting; Xue, Yong-Qi

    2012-11-01

    Integrating molecular imaging technology and hyperspectral technology, a novel molecular hyperspectral imaging (MHSI) system based on AOTF was presented. The system consists of microscope, spectrometer, matrix CCD, image collection card and computer. The system's performance was synthetically evaluated referring every part's performance. The spectral range of the MHSI system is from 550 to 1 000 nm. Two hundred twenty five bands can be continuously captured at a time. The spectral resolution is less than 2 nm. The spatial resolution is about 0.061 5 microm. CCD acquisition speed achieved 2.612 5 s x B(-1) in the integration mode and about 0.11 micros x B(-1) in the non-integration mode. Due to the infection of lamp, a spectral curve extracted directly from the original hyperspectral data can not truly present biochemical character and needs to be corrected. The paper proposes the gray correction coefficient algorithm with spatial dimension and spectral dimension, and gives concrete realization of the algorithm. Taking the sample of leukemia blood, by comparing the single-band images, pseudo-color images and spectra before and after correction, the results indicate the effectiveness of correction algorithm. The corrected data is effective for subsequent analysis. PMID:23387200

  4. Ultrafast molecular imaging by laser-induced electron diffraction

    SciTech Connect

    Peters, M.; Nguyen-Dang, T. T.; Cornaggia, C.; Saugout, S.; Charron, E.; Keller, A.; Atabek, O.

    2011-05-15

    We address the feasibility of imaging geometric and orbital structures of a polyatomic molecule on an attosecond time scale using the laser-induced electron diffraction (LIED) technique. We present numerical results for the highest molecular orbitals of the CO{sub 2} molecule excited by a near-infrared few-cycle laser pulse. 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.

  5. Imaging the molecular dynamics of dissociative electron attachment to water

    SciTech Connect

    Adaniya, Hidihito; Rudek, B.; Osipov, Timur; Haxton, Dan; Weber, Thorsten; Rescigno, Thomas N.; McCurdy, C.W.; Belkacem, Ali

    2009-10-19

    Momentum imaging experiments on dissociative electron attachment to the water molecule are combined with ab initio theoretical calculations of the angular dependence of the quantum mechanical amplitude for electron attachment to provide a detailed picture of the molecular dynamics of dissociation attachment via the two lowest energy Feshbach resonances. The combination of momentum imaging experiments and theory can reveal dissociation dynamics for which the axial recoil approximation breaks down and thus provides a powerful reaction microscope for DEA to polyatomics.

  6. Numerical solution of boundary-integral equations for molecular electrostatics.

    PubMed

    Bardhan, Jaydeep P

    2009-03-01

    Numerous molecular processes, such as ion permeation through channel proteins, are governed by relatively small changes in energetics. As a result, theoretical investigations of these processes require accurate numerical methods. In the present paper, we evaluate the accuracy of two approaches to simulating boundary-integral equations for continuum models of the electrostatics of solvation. The analysis emphasizes boundary-element method simulations of the integral-equation formulation known as the apparent-surface-charge (ASC) method or polarizable-continuum model (PCM). In many numerical implementations of the ASC/PCM model, one forces the integral equation to be satisfied exactly at a set of discrete points on the boundary. We demonstrate in this paper that this approach to discretization, known as point collocation, is significantly less accurate than an alternative approach known as qualocation. Furthermore, the qualocation method offers this improvement in accuracy without increasing simulation time. Numerical examples demonstrate that electrostatic part of the solvation free energy, when calculated using the collocation and qualocation methods, can differ significantly; for a polypeptide, the answers can differ by as much as 10 kcal/mol (approximately 4% of the total electrostatic contribution to solvation). The applicability of the qualocation discretization to other integral-equation formulations is also discussed, and two equivalences between integral-equation methods are derived. PMID:19275391

  7. Multimodality 3-Dimensional Image Integration for Congenital Cardiac Catheterization

    PubMed Central

    2014-01-01

    Cardiac catheterization procedures for patients with congenital and structural heart disease are becoming more complex. New imaging strategies involving integration of 3-dimensional images from rotational angiography, magnetic resonance imaging (MRI), computerized tomography (CT), and transesophageal echocardiography (TEE) are employed to facilitate these procedures. We discuss the current use of these new 3D imaging technologies and their advantages and challenges when used to guide complex diagnostic and interventional catheterization procedures in patients with congenital heart disease. PMID:25114757

  8. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    PubMed Central

    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

  9. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    SciTech Connect

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

    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.

  10. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    SciTech Connect

    Baba, Justin S; Endres, Christopher; Foss, Catherine; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard Jr, James Samuel; Lee, Seung Joon; McKisson, John; Smith, Mark F.; Stolin, Alexander; Weisenberger, Andrew G.; Pomper, Martin

    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.

  11. Polarimetric 3D integral imaging in photon-starved conditions.

    PubMed

    Carnicer, Artur; Javidi, Bahram

    2015-03-01

    We develop a method for obtaining 3D polarimetric integral images from elemental images recorded in low light illumination conditions. Since photon-counting images are very sparse, calculation of the Stokes parameters and the degree of polarization should be handled carefully. In our approach, polarimetric 3D integral images are generated using the Maximum Likelihood Estimation and subsequently reconstructed by means of a Total Variation Denoising filter. In this way, polarimetric results are comparable to those obtained in conventional illumination conditions. We also show that polarimetric information retrieved from photon starved images can be used in 3D object recognition problems. To the best of our knowledge, this is the first report on 3D polarimetric photon counting integral imaging. PMID:25836861

  12. Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

    PubMed Central

    Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

    2011-01-01

    The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

  13. Biomedical Applications of Functionalized Hollow Mesoporous Silica Nanoparticles: Focusing on Molecular Imaging

    PubMed Central

    Shi, Sixiang; Chen, Feng; Cai, Weibo

    2013-01-01

    Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle (MSN), have recently gained increasing interest due to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in engineering of functionalized HMSNs (i.e. f-HMSNs) with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this review article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, positron emission tomography, magnetic resonance, and ultrasound imaging in preclinical studies. Lastly, we also discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy. PMID:24279491

  14. Imaging vector fields using Line Integral Convolution

    SciTech Connect

    Cabral, B.; Leedom, L.C.

    1993-03-01

    Imaging vector fields has applications in science, art, image processing and special effects. An effective new approach is to use linear and curvilinear filtering techniques to locally blur textures along a vector field. This approach builds on several previous texture generation and filtering techniques. It is, however, unique because it is local, one-dimensional and independent of any predefined geometry or texture. The technique is general and capable of imaging arbitrary two- and three-dimensional vector fields. The local one-dimensional nature of the algorithm lends itself to highly parallel and efficient implementations. Furthermore, the curvilinear filter is capable of rendering detail on very intricate vector fields. Combining this technique with other rendering and image processing techniques -- like periodic motion filtering -- results in richly informative and striking images. The technique can also produce novel special effects.

  15. Image integrity verification in medical information systems.

    PubMed

    Lenti, Jozsef; Lovanyi, Istvan

    2003-01-01

    In nowadays it is a major objective to protect healthcare information against unauthorized access. Comparing conventional and electronic management of medical images the later one demands much more complex security measures. We propose a new scenario for watermark data buildup and embedding which is independent from the applied watermarking technology. In our proposed method the embedded watermark data is dependant on image and patient information too. The proposed watermark buildup method provides watermark information where it is small in size and represents a unique digest of the image and image related data. The embedded data can be considered unique with high probability even if the same algorithm was used in different medical information systems. Described procedures ensure new, more secure links between image and related data, offering further perspectives in smartcard implementations. PMID:14664001

  16. Recent Progress in Molecular Recognition Imaging Using Atomic Force Microscopy.

    PubMed

    Senapati, Subhadip; Lindsay, Stuart

    2016-03-15

    Atomic force microscopy (AFM) is an extremely powerful tool in the field of bionanotechnology because of its ability to image single molecules and make measurements of molecular interaction forces with piconewton sensitivity. It works in aqueous media, enabling studies of molecular phenomenon taking place under physiological conditions. Samples can be imaged in their near-native state without any further modifications such as staining or tagging. The combination of AFM imaging with the force measurement added a new feature to the AFM technique, that is, molecular recognition imaging. Molecular recognition imaging enables mapping of specific interactions between two molecules (one attached to the AFM tip and the other to the imaging substrate) by generating simultaneous topography and recognition images (TREC). Since its discovery, the recognition imaging technique has been successfully applied to different systems such as antibody-protein, aptamer-protein, peptide-protein, chromatin, antigen-antibody, cells, and so forth. Because the technique is based on specific binding between the ligand and receptor, it has the ability to detect a particular protein in a mixture of proteins or monitor a biological phenomenon in the native physiological state. One key step for recognition imaging technique is the functionalization of the AFM tips (generally, silicon, silicon nitrides, gold, etc.). Several different functionalization methods have been reported in the literature depending on the molecules of interest and the material of the tip. Polyethylene glycol is routinely used to provide flexibility needed for proper binding as a part of the linker that carries the affinity molecule. Recently, a heterofunctional triarm linker has been synthesized and successfully attached with two different affinity molecules. This novel linker, when attached to AFM tip, helped to detect two different proteins simultaneously from a mixture of proteins using a so-called "two

  17. Veni, vidi, vici: in vivo molecular imaging of immune response.

    PubMed

    Gross, Shimon; Moss, Britney L; Piwnica-Worms, David

    2007-10-01

    "I came, I saw, I conquered," Julius Caesar proclaimed, highlighting the importance of direct visualization as a winning strategy. Continuing the "From the Field" series (see Editorial [2007] 26, 131), Gross et al. summarize how modern molecular imaging techniques can successfully dissect the complexities of immune response in vivo. PMID:17967405

  18. Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.

    PubMed

    Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

    2014-10-29

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, (64)Cu(2+), Fe(3+)). Therefore, MNP can serve not only as a photoacoustic contrast agent, but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation. PMID:25292385

  19. Transferring Biomarker into Molecular Probe: Melanin Nanoparticle as a Naturally Active Platform for Multimodality Imaging

    PubMed Central

    2015-01-01

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, 64Cu2+, Fe3+). Therefore, MNP can serve not only as a photoacoustic contrast agent, but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation. PMID:25292385

  20. Multi-modality systems for molecular tomographic imaging

    NASA Astrophysics Data System (ADS)

    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.

  1. Compression of 3D integral images using wavelet decomposition

    NASA Astrophysics Data System (ADS)

    Mazri, Meriem; Aggoun, Amar

    2003-06-01

    This paper presents a wavelet-based lossy compression technique for unidirectional 3D integral images (UII). The method requires the extraction of different viewpoint images from the integral image. A single viewpoint image is constructed by extracting one pixel from each microlens, then each viewpoint image is decomposed using a Two Dimensional Discrete Wavelet Transform (2D-DWT). The resulting array of coefficients contains several frequency bands. The lower frequency bands of the viewpoint images are assembled and compressed using a 3 Dimensional Discrete Cosine Transform (3D-DCT) followed by Huffman coding. This will achieve decorrelation within and between 2D low frequency bands from the different viewpoint images. The remaining higher frequency bands are Arithmetic coded. After decoding and decompression of the viewpoint images using an inverse 3D-DCT and an inverse 2D-DWT, each pixel from every reconstructed viewpoint image is put back into its original position within the microlens to reconstruct the whole 3D integral image. Simulations were performed on a set of four different grey level 3D UII using a uniform scalar quantizer with deadzone. The results for the average of the four UII intensity distributions are presented and compared with previous use of 3D-DCT scheme. It was found that the algorithm achieves better rate-distortion performance, with respect to compression ratio and image quality at very low bit rates.

  2. Molecular Imaging of Apoptosis: From Micro to Macro

    PubMed Central

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

    2015-01-01

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

  3. Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

    PubMed Central

    Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

    2015-01-01

    Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

  4. Practical Methods for Molecular In Vivo Optical Imaging

    PubMed Central

    Chen, Hannah; Thorne, Stephen H

    2011-01-01

    Traditional approaches for translating observations of molecular events into the context of a living organism have suffered from the requirements for either sacrificing animals at multiple time points prior to labor-intensive analyses of multiple tissues, or have relied on subjective observations or measurements of the animals over time. Recently an explosion of dedicated animal imaging modalities and the release of modified clinical imaging devices dedicated for animal imaging have allowed for the design of quantitative real time experiments incorporating fewer animals and providing whole animal analyses. Of these modalities, optical imaging (bioluminescence and fluorescence) has emerged as a powerful research tool, allowing investigators with limited whole animal imaging expertise to rapidly and inexpensively translate models produced in cellular assays into the context of a living animal. Here we will outline the steps necessary for translation of models established in culture systems into rodents. PMID:25419262

  5. Silicon sample holder for molecular beam epitaxy on pre-fabricated integrated circuits

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E. (Inventor); Grunthaner, Paula J. (Inventor); Grunthaner, Frank J. (Inventor)

    1994-01-01

    The sample holder of the invention is formed of the same semiconductor crystal as the integrated circuit on which the molecular beam expitaxial process is to be performed. In the preferred embodiment, the sample holder comprises three stacked micro-machined silicon wafers: a silicon base wafer having a square micro-machined center opening corresponding in size and shape to the active area of a CCD imager chip, a silicon center wafer micro-machined as an annulus having radially inwardly pointing fingers whose ends abut the edges of and center the CCD imager chip within the annulus, and a silicon top wafer micro-machined as an annulus having cantilevered membranes which extend over the top of the CCD imager chip. The micro-machined silicon wafers are stacked in the order given above with the CCD imager chip centered in the center wafer and sandwiched between the base and top wafers. The thickness of the center wafer is about 20% less than the thickness of the CCD imager chip. Preferably, four titanium wires, each grasping the edges of the top and base wafers, compress all three wafers together, flexing the cantilever fingers of the top wafer to accommodate the thickness of the CCD imager chip, acting as a spring holding the CCD imager chip in place.

  6. Design and Applications of Bispecific Heterodimers: Molecular Imaging and beyond

    PubMed Central

    2015-01-01

    Ligand-based molecular imaging probes have been designed with high affinity and specificity for monitoring biological process and responses. Single-target recognition by traditional probes can limit their applicability for disease detection and therapy because synergistic action between disease mediators and different receptors is often involved in disease progression. Consequently, probes that can recognize multiple targets should demonstrate higher targeting efficacy and specificity than their monospecific peers. This concept has been validated by multiple bispecific heterodimer-based imaging probes that have demonstrated promising results in several animal models. This review summarizes the design strategies for bispecific peptide- and antibody-based heterodimers and their applications in molecular targeting and imaging. The design and application of bispecific heterodimer-conjugated nanomaterials are also discussed. PMID:24738564

  7. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    SciTech Connect

    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.

  8. Noninvasive tumor oxygen imaging by photoacoustic lifetime imaging integrated with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Shao, Qi; Biel, Merrill A.; Ashkenazi, Shai

    2014-03-01

    Oxygen plays a major role in cancer biology and tumor progression. In PDT, the reduction in efficacy is directly related to lack of oxygen because its molecular mechanism relies on oxygen as an energy mediator. Measuring tumor oxygenation can provide physicians with better diagnosis and optimization of treatment plans. However, clinical tools for directly assessing tissue oxygenation are limited. The gold standard is oxygen needle electrode, which is invasive and measures oxygen level at a single location. We present our work on developing a combined treatment-imaging modality that integrates PDT and photoacoustic oxygen imaging. We propose a system designed for clinical treatments of cancer of the oral cavity. Tissue oxygen imaging is performed by applying Photoacoustic Lifetime Imaging (PALI). This technology relies on photoacoustic probing of oxygen-dependent excitation lifetime of Methylene Blue. The dye is excited by the same wavelength of illumination source for PDT. Once excited, the population of photosensitizer molecules at triplet state has a lifetime depending on the oxygen level. The transition from excited triplet state to ground state can be probe by another laser, which generate photoacoustic signal that is used to map the lifetime. The lifetime map is then converted to pO2 distribution. We expect that PDT efficacy can be improved by applying PALI imaging feedback in real-time to determine, and individually optimize, O2-enriched gas breathing parameters and PDT light-dose during treatment. Successful implementation of PALI in PDT can also drive its application in guiding other cancer treatments that are affected by hypoxia.

  9. Integrating X-ray fluorescence and infrared imaging microspectroscopies for comprehensive characterization of an acetaminophen model pharmaceutical.

    PubMed

    Patterson, Brian M; Havrilla, George J

    2006-05-01

    The integration of full spectral images using the complementary microspectroscopic imaging techniques X-ray fluorescence and Fourier transform infrared is demonstrated. This effort surpasses previous work in that a single chemometric software package is used to elicit chemical information from the integrated spectroscopic images. Integrating these two complementary spectroscopic methods provides both elemental and molecular spatial distribution within a specimen. The critical aspect in this work is using full spectral maps from each pixel within the image and subsequent processing with chemometric tools to provide integrated chemical information. This integration enables a powerful approach to more comprehensive materials characterization. Issues addressed include sample registration and beam penetration depth and how each affects post-processing. An inorganic salt and an acetaminophen pharmaceutical model mixture demonstrate the power of integrating these techniques with chemometric software. PMID:16756696

  10. TOPICAL REVIEW: In vivo molecular and genomic imaging: new challenges for imaging physics

    NASA Astrophysics Data System (ADS)

    Cherry, Simon R.

    2004-02-01

    The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

  11. Optical slicing of large scenes by synthetic aperture integral imaging

    NASA Astrophysics Data System (ADS)

    Navarro, Héctor; Saavedra, Genaro; Molina, Ainhoa; Martínez-Corral, Manuel; Martínez-Cuenca, Raúl; Javidi, Bahram

    2010-04-01

    Integral imaging (InI) technology was created with the aim of providing the binocular observers of monitors, or matrix display devices, with auto-stereoscopic images of 3D scenes. However, along the last few years the inventiveness of researches has allowed to find many other interesting applications of integral imaging. Examples of this are the application of InI in object recognition, the mapping of 3D polarization distributions, or the elimination of occluding signals. One of the most interesting applications of integral imaging is the production of views focused at different depths of the 3D scene. This application is the natural result of the ability of InI to create focal stacks from a single input image. In this contribution we present new algorithm for this optical slicing application, and show that it is possible the 3D reconstruction with improved lateral resolution.

  12. CMOS Time-Resolved, Contact, and Multispectral Fluorescence Imaging for DNA Molecular Diagnostics

    PubMed Central

    Guo, Nan; Cheung, Ka Wai; Wong, Hiu Tung; Ho, Derek

    2014-01-01

    Instrumental limitations such as bulkiness and high cost prevent the fluorescence technique from becoming ubiquitous for point-of-care deoxyribonucleic acid (DNA) detection and other in-field molecular diagnostics applications. The complimentary metal-oxide-semiconductor (CMOS) technology, as benefited from process scaling, provides several advanced capabilities such as high integration density, high-resolution signal processing, and low power consumption, enabling sensitive, integrated, and low-cost fluorescence analytical platforms. In this paper, CMOS time-resolved, contact, and multispectral imaging are reviewed. Recently reported CMOS fluorescence analysis microsystem prototypes are surveyed to highlight the present state of the art. PMID:25365460

  13. Molecular structure and elastic properties of thermotropic liquid crystals: Integrated molecular dynamics—Statistical mechanical theory vs molecular field approach

    NASA Astrophysics Data System (ADS)

    Capar, M. Ilk; Nar, A.; Ferrarini, A.; Frezza, E.; Greco, C.; Zakharov, A. V.; Vakulenko, A. A.

    2013-03-01

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio.

  14. Molecular structure and elastic properties of thermotropic liquid crystals: integrated molecular dynamics--statistical mechanical theory vs molecular field approach.

    PubMed

    Ilk Capar, M; Nar, A; Ferrarini, A; Frezza, E; Greco, C; Zakharov, A V; Vakulenko, A A

    2013-03-21

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio

  15. Multi-modality molecular imaging: pre-clinical laboratory configuration

    NASA Astrophysics Data System (ADS)

    Wu, Yanjun; Wellen, Jeremy W.; Sarkar, Susanta K.

    2006-02-01

    In recent years, the prevalence of in vivo molecular imaging applications has rapidly increased. Here we report on the construction of a multi-modality imaging facility in a pharmaceutical setting that is expected to further advance existing capabilities for in vivo imaging of drug distribution and the interaction with their target. The imaging instrumentation in our facility includes a microPET scanner, a four wavelength time-domain optical imaging scanner, a 9.4T/30cm MRI scanner and a SPECT/X-ray CT scanner. An electronics shop and a computer room dedicated to image analysis are additional features of the facility. The layout of the facility was designed with a central animal preparation room surrounded by separate laboratory rooms for each of the major imaging modalities to accommodate the work-flow of simultaneous in vivo imaging experiments. This report will focus on the design of and anticipated applications for our microPET and optical imaging laboratory spaces. Additionally, we will discuss efforts to maximize the daily throughput of animal scans through development of efficient experimental work-flows and the use of multiple animals in a single scanning session.

  16. ADVANCES IN MOLECULAR IMAGING OF PANCREATIC BETA CELLS

    PubMed Central

    Lin, Mai; Lubag, Angelo; McGuire, Michael J.; Seliounine, Serguei Y.; Tsyganov, Edward N.; Antich, Peter P.; Sherry, A. Dean; Brown, Kathlynn C.; Sun, Xiankai

    2009-01-01

    The development of non-invasive imaging methods for early diagnosis of the beta cell associated metabolic diseases, including type 1 and type 2 diabetes (T1D and T2D), has recently drawn considerable interest from the molecular imaging community as well as clinical investigators. Due to the challenges imposed by the location of the pancreas, the sparsely dispersed beta cell population within the pancreas, and the poor understanding of the pathogenesis of the diseases, clinical diagnosis of beta cell abnormalities is still limited. Current diagnostic methods are invasive, often inaccurate, and usually performed post-onset of the disease. Advances in imaging techniques for probing beta cell mass and function are needed to address this critical health care problem. A variety of currently available imaging techniques have been tested for the assessment of the pancreatic beta cell islets. Here we discuss the current advances in magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and nuclear imaging for the study of beta cell diseases. Spurred by early successes in nuclear imaging techniques for beta cells, especially positron emission tomography (PET), the need for beta cell specific ligands has expanded. Progress in the field for obtaining such ligands is presented. Additionally, we report our preliminary efforts of developing such a peptidic ligand for PET imaging of the pancreatic beta cells. PMID:18508529

  17. OsiriX plugin for integrated cardiac imaging research

    NASA Astrophysics Data System (ADS)

    Hüllebrand, Markus; Hennemuth, Anja; Messroghli, Daniel; Kühne, Titus

    2014-03-01

    Strongly evolving imaging technologies such as magnetic resonance imaging (MRI) nowadays provide a multitude of new complementary techniques for the analysis of cardiovascular tissue properties, function, and hemodynamics. The purpose of the presented work is to provide a research tool, which enables a quick validation of newly developed imaging techniques and supports the co-development of clinically usable analysis tools, which allow an integration with existing complementary examination methods. The concepts combined to this end consist of an integration with the open source research PACS OsiriX, an advanced heuristic DICOM classification and preprocessing as well as an integrative data model, which accumulates patient-specific image data, results and the data relations. Specific processing and analysis plugins can easily be integrated in such a way that they use the data integration and visualization infrastructure as well as results from other existing plugins. The presented example applications, such as the evaluation of slice orientations for cardiac function quantification or the integrated analysis of different types of image data for diagnosis of myocarditis show that the provided tool can be successfully used for a multitude of research applications in cardiovascular imaging.

  18. Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography

    NASA Astrophysics Data System (ADS)

    Maji, Dolonchampa; Solomon, Metasebya; Nguyen, Annie; Pierce, Richard A.; Woodard, Pamela K.; Akers, Walter J.; Achilefu, Samuel; Culver, Joseph P.; Abendschein, Dana R.; Shokeen, Monica

    2014-11-01

    Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture.

  19. Angular momentum in molecular quantum mechanical integral evaluation

    NASA Astrophysics Data System (ADS)

    Dunlap, Brett I.

    2005-01-01

    Solid-harmonic derivatives of quantum-mechanical integrals over Gaussian transforms of scalar, or radial, atomic basis functions create angular momentum about each center. Generalized Gaunt coefficients limit the amount of cross differentiation for multi-center integrals to ensure that cross differentiation does not affect the total angular momentum. The generalized Gaunt coefficients satisfy a number of other selection rules, which are exploited in a new computer code for computing forces in analytic density-functional theory based on robust and variational fitting of the Kohn-Sham potential. Two-center exponents are defined for four or more solid-harmonic differentiations of matrix elements. Those differentiations can either build up angular momentum about the centers or give forces on molecular potential-energy surfaces, thus generalized Gaunt coefficients of order greater than the number of centers are considered. These 4- j generalized Gaunt coefficients and two-center exponents are used to compute the first derivatives of all integrals involving all the Gaussian exponents on a triplet of centers at once. First all angular factors are contracted with the corresponding part of the linear-combination-of-atomic-orbitals density matrix. This intermediate quantity is then reused for the nuclear attraction integral and the integrals corresponding to each basis function in the analytic fit of the Kohn-Sham potential in the muffin-tin-like, but analytic, Slater-Roothaan method that allows molecules to dissociate into atoms having any desired energy, including the experimental electronic energy. The energy is stationary in all respects and all forces precisely agree with a previous code in tests on small molecules. During geometry optimization of an icosahedral C 720 fullerene computing these angular factors and transforming them via the 4- j generalized Gaunt coefficient takes more than sixty percent of the total computer time. These same angular factors could be used

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Integration of virtual and real scenes within an integral 3D imaging environment

    NASA Astrophysics Data System (ADS)

    Ren, Jinsong; Aggoun, Amar; McCormick, Malcolm

    2002-11-01

    The Imaging Technologies group at De Montfort University has developed an integral 3D imaging system, which is seen as the most likely vehicle for 3D television avoiding psychological effects. To create real fascinating three-dimensional television programs, a virtual studio that performs the task of generating, editing and integrating the 3D contents involving virtual and real scenes is required. The paper presents, for the first time, the procedures, factors and methods of integrating computer-generated virtual scenes with real objects captured using the 3D integral imaging camera system. The method of computer generation of 3D integral images, where the lens array is modelled instead of the physical camera is described. In the model each micro-lens that captures different elemental images of the virtual scene is treated as an extended pinhole camera. An integration process named integrated rendering is illustrated. Detailed discussion and deep investigation are focused on depth extraction from captured integral 3D images. The depth calculation method from the disparity and the multiple baseline method that is used to improve the precision of depth estimation are also presented. The concept of colour SSD and its further improvement in the precision is proposed and verified.

  2. Molecular Imaging Using Nanoparticle Quenchers of Cerenkov Luminescence

    PubMed Central

    Thorek, Daniel L.J.; Das, Sudeep; Grimm, Jan

    2014-01-01

    Cerenkov luminescence (CL) imaging is an emerging technique that collects the visible photons produced by radioisotopes. Here, we have investigated molecular imaging strategies by modulating CL signal off. Utilizing a combination of clinically approved agents, and their analogues, we demonstrate the noninvasive molecularly specific detection of cancer. CL was modulated in vitro in a dose dependent manner using approved small molecules (Lymphazurin), as well as the clinically approved Feraheme and other preclinical superparamagnetic iron oxide nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies were pursued. [18F]-FDG was imaged by PET and CL in tumors prior to and following accumulation of nanoparticles. Initially, non-targeted particles were administered to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a control negative cell line) was used. Targeting hSSTr2 with octreotate-conjugated SPIO, we demonstrate quenched CL enabling non-invasive distinction between tumors’ molecular expression profiles. In this work, we demonstrate quenching of Cerenkov emissions in several proof of principle models using a combination of approved agents and nanoparticle platforms to provide disease relevant information including tumor vascularity and specific antigen expression. PMID:24861843

  3. Molecular imaging using nanoparticle quenchers of Cerenkov luminescence.

    PubMed

    Thorek, Daniel L J; Das, Sudeep; Grimm, Jan

    2014-09-24

    Cerenkov luminescence (CL) imaging is an emerging technique that collects the visible photons produced by radioisotopes. Here, molecular imaging strategies are investigated that switch the CL signal off. The noninvasive molecularly specific detection of cancer is demonstrated utilizing a combination of clinically approved agents, and their analogues. CL is modulated in vitro in a dose dependent manner using approved small molecules (Lymphazurin), as well as the clinically approved Feraheme and other preclinical superparamagnetic iron oxide nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies are pursued. [(18) F]-FDG is imaged by PET and CL in tumors prior to and following accumulation of nanoparticles. Initially, non-targeted particles are administered to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a control negative cell line) is used. Targeting hSSTr2 with octreotate-conjugated SPIO, quenched CL enabling non-invasive distinction between tumors' molecular expression profiles is demonstrated. In this work, the quenching of Cerenkov emissions is demonstrated in several proof of principle models using a combination of approved agents and nanoparticle platforms to provide disease relevant information including tumor vascularity and specific antigen expression. PMID:24861843

  4. X-ray diffraction topography image materials by molecular probe

    NASA Astrophysics Data System (ADS)

    Hentschel, Manfred P.; Lange, Axel; Schors, Joerg; Wald, Oliver

    2005-05-01

    Crystallinity, composition, homogeneity and anisotropy determine the mechanical properties of materials significantly, but the performance of most non-destructive techniques is too poor for measuring these micro structures as they are optimized for finding individual flaws/defects. X-ray (wide angle) Diffraction Topography by single beam scanning images molecular information at a spatial resolution of several ten micrometers even in three dimensions. Especially for the non-destructive characterization of composite materials, they provide additional capabilities by crystallographic contrast by the molecular/atomic probe. The different material phases of compounds and their molecular orientation can be imaged e.g. fibers or polymer chain orientation in composites: A sample is scanned or rotated, while only part of the scattering pattern is pointing at an X-ray detector area. Three different methods have been developed: i) planar X-ray Scanning Topography at one or more pre-selected scattering angles provides high contrast of different phases of components. ii) X-Ray Rotation Topography reveals the texture angle of composite fibers and chain polymers. iii) X-ray Diffraction Microscopy images the texture and phase distribution of transversal sections of the material. The principles of Wide Angle X-Ray Diffraction Topography are explained and examples of investigations will be presented. They combine the advantages of radiographic imaging and crystal structure information. The applied X-ray energies are much lower than in NDT radiography, which recommends preferably the application to light weight materials.

  5. Network of fully integrated multispecialty hospital imaging systems

    NASA Astrophysics Data System (ADS)

    Dayhoff, Ruth E.; Kuzmak, Peter M.

    1994-05-01

    The Department of Veterans Affairs (VA) DHCP Imaging System records clinically significant diagnostic images selected by medical specialists in a variety of departments, including radiology, cardiology, gastroenterology, pathology, dermatology, hematology, surgery, podiatry, dental clinic, and emergency room. These images are displayed on workstations located throughout a medical center. All images are managed by the VA's hospital information system, allowing integrated displays of text and image data across medical specialties. Clinicians can view screens of `thumbnail' images for all studies or procedures performed on a selected patient. Two VA medical centers currently have DHCP Imaging Systems installed, and others are planned. All VA medical centers and other VA facilities are connected by a wide area packet-switched network. The VA's electronic mail software has been modified to allow inclusion of binary data such as images in addition to the traditional text data. Testing of this multimedia electronic mail system is underway for medical teleconsultation.

  6. Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology

    PubMed Central

    Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

    2014-01-01

    Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. PMID:25250092

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

    NASA Astrophysics Data System (ADS)

    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

  8. Inter-subject MR-PET image registration and integration

    SciTech Connect

    Lin, K.P.; Chen, T.S.; Yao, W.F.

    1996-12-31

    A MR-PET inter-subject image integration technique is developed to provide more precise anatomical location based on a template MR image, and to examine the anatomical variation in sensory-motor stimulation or to obtain cross-subject signal averaging to enhance the delectability of focal brain activity detected by different subject PET images. In this study, a multimodality intrasubject image registration procedure is firstly applied to align MR and PET images of the same subject. The second procedure is to estimate an elastic image transformation that can nonlinearly deform each 3D brain MR image and map them to the template MR image. The estimation procedure of the elastic image transformation is based on a strategy that searches the best local image match to achieve an optimal global image match, iteratively. The final elastic image transformation estimated for each subject will then be used to deform the MR-PET registered PET image. After the nonlinear PET image deformation, MR-PET intersubject mapping, averaging, and fusing are simultaneously accomplished. The developed technique has been implemented to an UNIX based workstation with Motif window system. The software named Elastic-IRIS has few requirements of user interaction. The registered anatomical location of 10 different subjects has a standard deviation of {approximately}2mm. in the x, y, and z directions. The processing time for one MR-PET inter-subject registration ranged from 20 to 30 minutes on a SUN SPARC-20.

  9. Integration of content-based image retrieval system with PACS

    NASA Astrophysics Data System (ADS)

    Ghanem, Ahmed M.; Rasmy, M. Emad M.; Kadah, Yasser M.

    2001-08-01

    Content-based image retrieval (CBIR) provides a flexible means of searching a digital image library based on the description of the desired image. In this paper, we integrate CBIR, RIS, and HIS in PACS to allow retrieving images of similar features. Once the system finds the related images, the embedded CBIR retrieves the radiological reports and medical records of the output images, which can be used to increase diagnostic accuracy. The CBIR system is implemented on a separate server based on multi-resolution image matching. To reduce the retrieval loading on the server and network shanks, a procedure to use copies of images that are temporarily located in some workstations in the PACS is applied. These copies are stored on a temporary database space created on the different workstations. A new image retrieval management server contains image IDs in the database and the IP addresses of the workstations containing temporary image copies. Data on the management server are continuously updated with each addition or retrieval operation. When a display workstation needs a specific image, it sends a request with the required image ID to the management server, which in turn replies with the IP of the workstation containing the inquired image ID.

  10. Multiview image integration system for glassless 3D display

    NASA Astrophysics Data System (ADS)

    Ando, Takahisa; Mashitani, Ken; Higashino, Masahiro; Kanayama, Hideyuki; Murata, Haruhiko; Funazou, Yasuo; Sakamoto, Naohisa; Hazama, Hiroshi; Ebara, Yasuo; Koyamada, Koji

    2005-03-01

    We have developed a multi-view image integration system, which combines seven parallax video images into a single video image so that it fits the parallax barrier. The apertures of this barrier are not stripes but tiny rectangles that are arranged in the shape of stairs. Commodity hardware is used to satisfy a specification which requires that the resolution of each parallax video image is SXGA(1645×800 pixel resolution), the resulting integrated image is QUXGA-W(3840×2400 pixel resolution), and the frame rate is fifteen frames per second. The point is that the system can provide with QUXGA-W video image, which corresponds to 27MB, at 15fps, that is about 2Gbps. Using the integration system and a Liquid Crystal Display with the parallax barrier, we can enjoy an immersive live video image which supports seven viewpoints without special glasses. In addition, since the system can superimpose the CG images of the relevant seven viewpoints into the live video images, it is possible to communicate with remote users by sharing a virtual object.

  11. Compressive spectral integral imaging using a microlens array

    NASA Astrophysics Data System (ADS)

    Feng, Weiyi; Rueda, Hoover; Fu, Chen; Qian, Chen; Arce, Gonzalo R.

    2016-05-01

    In this paper, a compressive spectral integral imaging system using a microlens array (MLA) is proposed. This system can sense the 4D spectro-volumetric information into a compressive 2D measurement image on the detector plane. In the reconstruction process, the 3D spatial information at different depths and the spectral responses of each spatial volume pixel can be obtained simultaneously. In the simulation, sensing of the 3D objects is carried out by optically recording elemental images (EIs) using a scanned pinhole camera. With the elemental images, a spectral data cube with different perspectives and depth information can be reconstructed using the TwIST algorithm in the multi-shot compressive spectral imaging framework. Then, the 3D spatial images with one dimensional spectral information at arbitrary depths are computed using the computational integral imaging method by inversely mapping the elemental images according to geometrical optics. The simulation results verify the feasibility of the proposed system. The 3D volume images and the spectral information of the volume pixels can be successfully reconstructed at the location of the 3D objects. The proposed system can capture both 3D volumetric images and spectral information in a video rate, which is valuable in biomedical imaging and chemical analysis.

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

    NASA Astrophysics Data System (ADS)

    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

  13. [Molecular hyperspectral imaging (MHSI) system and application in biochemical medicine].

    PubMed

    Liu, Hong-Ying; Li, Qing-Li; Wang, Yi-Ting; Liu, Jin-Gao; Xue, Yong-Qi

    2011-10-01

    A novel molecular hyperspectral imaging (MHSI) system based on AOTF (acousto-optic tunable filters) was presented. The system consists of microscope, AOTF-based spectrometer, matrix CCD, image collection card and computer. The spectral range of the MHSI is from 550 to 1 000 nm. The spectral resolution is less than 2 nm, and the spatial resolution is about 0.3 microm. This paper has also presented that spectral curves extracted from the corrected hyperspectral data of the sample, which have been preprocessed by the gray correction coefficient, can more truly represent biochemical characteristic of the sample. The system can supply not only single band images in the visible range, but also spectrum curve of random pixel of sample image. This system can be widely used in various fields of biomedicine, clinical medicine, material science and microelectronics. PMID:22250515

  14. Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

    PubMed Central

    Lawler, James; Paragas, Jason; Jahrling, Peter B.; Mollura, Daniel J.

    2011-01-01

    Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. PMID:21422476

  15. Optimizing Central Nervous System Drug Development Using Molecular Imaging.

    PubMed

    Hargreaves, R J; Hoppin, J; Sevigny, J; Patel, S; Chiao, P; Klimas, M; Verma, A

    2015-07-01

    Advances in multimodality fusion imaging technologies promise to accelerate the understanding of the systems biology of disease and help in the development of new therapeutics. The use of molecular imaging biomarkers has been proven to shorten cycle times for central nervous system (CNS) drug development and thereby increase the efficiency and return on investment from research. Imaging biomarkers can be used to help select the molecules, doses, and patients most likely to test therapeutic hypotheses by stopping those that have little chance of success and accelerating those with potential to achieve beneficial clinical outcomes. CNS imaging biomarkers have the potential to drive new medical care practices for patients in the latent phases of progressive neurodegenerative disorders by enabling the detection, preventative treatment, and tracking of disease in a paradigm shift from today's approaches that have to see the overt symptoms of disease before treating it. PMID:25869938

  16. Growth, modification and integration of carbon nanotubes into molecular electronics

    NASA Astrophysics Data System (ADS)

    Moscatello, Jason P.

    Molecules are the smallest possible elements for electronic devices, with active elements for such devices typically a few Angstroms in footprint area. Owing to the possibility of producing ultra-high density devices, tremendous effort has been invested in producing electronic junctions by using various types of molecules. The major issues for molecular electronics include (1) developing an effective scheme to connect molecules with the present micro- and nano-technology, (2) increasing the lifetime and stabilities of the devices, and (3) increasing their performance in comparison to the state-of-the-art devices. In this work, we attempt to use carbon nanotubes (CNTs) as the interconnecting nanoelectrodes between molecules and microelectrodes. The ultimate goal is to use two individual CNTs to sandwich molecules in a cross-bar configuration while having these CNTs connected with microelectrodes such that the junction displays the electronic character of the molecule chosen. We have successfully developed an effective scheme to connect molecules with CNTs, which is scalable to arrays of molecular electronic devices. To realize this far reaching goal, the following technical topics have been investigated. (1) Synthesis of multi-walled carbon nanotubes (MWCNTs) by thermal chemical vapor deposition (T-CVD) and plasma-enhanced chemical vapor deposition (PECVD) techniques (Chapter 3). We have evaluated the potential use of tubular and bamboo-like MWCNTs grown by T-CVD and PE-CVD in terms of their structural properties. (2) Horizontal dispersion of MWCNTs with and without surfactants, and the integration of MWCNTs to microelectrodes using deposition by dielectrophoresis (DEP) (Chapter 4). We have systematically studied the use of surfactant molecules to disperse and horizontally align MWCNTs on substrates. In addition, DEP is shown to produce impurityfree placement of MWCNTs, forming connections between microelectrodes. We demonstrate the deposition density is tunable by

  17. Integrated molecular portrait of non-small cell lung cancers

    PubMed Central

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers

  18. A 128 x 128 CMOS Active Pixel Image Sensor for Highly Integrated Imaging Systems

    NASA Technical Reports Server (NTRS)

    Mendis, Sunetra K.; Kemeny, Sabrina E.; Fossum, Eric R.

    1993-01-01

    A new CMOS-based image sensor that is intrinsically compatible with on-chip CMOS circuitry is reported. The new CMOS active pixel image sensor achieves low noise, high sensitivity, X-Y addressability, and has simple timing requirements. The image sensor was fabricated using a 2 micrometer p-well CMOS process, and consists of a 128 x 128 array of 40 micrometer x 40 micrometer pixels. The CMOS image sensor technology enables highly integrated smart image sensors, and makes the design, incorporation and fabrication of such sensors widely accessible to the integrated circuit community.

  19. Recent Advances in Molecular Magnetic Resonance Imaging of Liver Fibrosis

    PubMed Central

    Li, Zhiming; Sun, Jihong; Yang, Xiaoming

    2015-01-01

    Liver fibrosis is a life-threatening disease with high morbidity and mortality owing to its diverse causes. Liver biopsy, as the current gold standard for diagnosing and staging liver fibrosis, has a number of limitations, including sample variability, relatively high cost, an invasive nature, and the potential of complications. Most importantly, in clinical practice, patients often reject additional liver biopsies after initiating treatment despite their being necessary for long-term follow-up. To resolve these problems, a number of different noninvasive imaging-based methods have been developed for accurate diagnosis of liver fibrosis. However, these techniques only reflect morphological or perfusion-related alterations in the liver, and thus they are generally only useful for the diagnosis of late-stage liver fibrosis (liver cirrhosis), which is already characterized by “irreversible” anatomic and hemodynamic changes. Thus, it is essential that new approaches are developed for accurately diagnosing early-stage liver fibrosis as at this stage the disease may be “reversed” by active treatment. The development of molecular MR imaging technology has potential in this regard, as it facilitates noninvasive, target-specific imaging of liver fibrosis. We provide an overview of recent advances in molecular MR imaging for the diagnosis and staging of liver fibrosis and we compare novel technologies with conventional MR imaging techniques. PMID:25874221

  20. Volumetric feature extraction and visualization of tomographic molecular imaging.

    PubMed

    Bajaj, Chandrajit; Yu, Zeyun; Auer, Manfred

    2003-01-01

    Electron tomography is useful for studying large macromolecular complex within their cellular context. The associate problems include crowding and complexity. Data exploration and 3D visualization of complexes require rendering of tomograms as well as extraction of all features of interest. We present algorithms for fully automatic boundary segmentation and skeletonization, and demonstrate their applications in feature extraction and visualization of cell and molecular tomographic imaging. We also introduce an interactive volumetric exploration and visualization tool (Volume Rover), which encapsulates implementations of the above volumetric image processing algorithms, and additionally uses efficient multi-resolution interactive geometry and volume rendering techniques for interactive visualization. PMID:14643216

  1. Molecular imaging with surface-enhanced CARS on nanostructures

    NASA Astrophysics Data System (ADS)

    Steuwe, Christian; Kaminski, Clemens F.; Baumberg, Jeremy J.; Mahajan, Sumeet

    2012-03-01

    Strongly localized electromagnetic fields in the vicinity of nanoparticles and nanogaps greatly enhance spectroscopic signals near them such as in surface-enhanced Raman spectroscopy (SERS). In this work we combine this plasmonic surface enhancement with coherent anti-Stokes Raman spectroscopy (CARS) on reproducible nanostructured surfaces. Surface-enhanced CARS (SECARS) gives rise to very strong enhancements and we find that an enhancement of ~105 can be obtained over standard CARS. Using our nanostructured surfaces, we demonstrate strong correlation between plasmon resonances and surface-enhanced CARS intensities. Furthermore, fast imaging of molecular monolayers is performed. Our work paves the way for reliable single molecule Raman spectroscopy and fast molecular imaging on plasmonic surfaces.

  2. Molecular imaging using a targeted magnetic resonance hyperpolarized biosensor.

    PubMed

    Schröder, Leif; Lowery, Thomas J; Hilty, Christian; Wemmer, David E; Pines, Alexander

    2006-10-20

    A magnetic resonance approach is presented that enables high-sensitivity, high-contrast molecular imaging by exploiting xenon biosensors. These sensors link xenon atoms to specific biomolecular targets, coupling the high sensitivity of hyperpolarized nuclei with the specificity of biochemical interactions. We demonstrated spatial resolution of a specific target protein in vitro at micromolar concentration, with a readout scheme that reduces the required acquisition time by >3300-fold relative to direct detection. This technique uses the signal of free hyperpolarized xenon to dramatically amplify the sensor signal via chemical exchange saturation transfer (CEST). Because it is approximately 10,000 times more sensitive than previous CEST methods and other molecular magnetic resonance imaging techniques, it marks a critical step toward the application of xenon biosensors as selective contrast agents in biomedical applications. PMID:17053143

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

    PubMed

    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. Multiple ray cluster rendering for interactive integral imaging system.

    PubMed

    Jiao, Shaohui; Wang, Xiaoguang; Zhou, Mingcai; Li, Weiming; Hong, Tao; Nam, Dongkyung; Lee, Jin-Ho; Wu, Enhua; Wang, Haitao; Kim, Ji-Yeun

    2013-04-22

    In this paper, we present an efficient Computer Generated Integral Imaging (CGII) method, called multiple ray cluster rendering (MRCR). Based on the MRCR, an interactive integral imaging system is realized, which provides accurate 3D image satisfying the changeable observers' positions in real time. The MRCR method can generate all the elemental image pixels within only one rendering pass by ray reorganization of multiple ray clusters and 3D content duplication. It is compatible with various graphic contents including mesh, point cloud, and medical data. Moreover, multi-sampling method is embedded in MRCR method for acquiring anti-aliased 3D image result. To our best knowledge, the MRCR method outperforms the existing CGII methods in both the speed performance and the display quality. Experimental results show that the proposed CGII method can achieve real-time computational speed for large-scale 3D data with about 50,000 points. PMID:23609712

  5. Non-invasive Optical Molecular Imaging for Cancer Detection

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

    Wachsmann, Jason; Peng, Fangyu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

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

    PubMed Central

    Wachsmann, Jason; Peng, Fangyu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

  8. Excited states of ribosome translocation revealed through integrative molecular modeling

    PubMed Central

    Whitford, Paul C.; Ahmed, Aqeel; Yu, Yanan; Hennelly, Scott P.; Tama, Florence; Spahn, Christian M. T.; Onuchic, José N.; Sanbonmatsu, Karissa Y.

    2011-01-01

    The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them. PMID:22080606

  9. Excited states of ribosome translocation revealed through integrative molecular modeling.

    PubMed

    Whitford, Paul C; Ahmed, Aqeel; Yu, Yanan; Hennelly, Scott P; Tama, Florence; Spahn, Christian M T; Onuchic, José N; Sanbonmatsu, Karissa Y

    2011-11-22

    The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them. PMID:22080606

  10. Quantum Thermal Bath for Path Integral Molecular Dynamics Simulation.

    PubMed

    Brieuc, Fabien; Dammak, Hichem; Hayoun, Marc

    2016-03-01

    The quantum thermal bath (QTB) method has been recently developed to account for the quantum nature of the nuclei by using standard molecular dynamics (MD) simulation. QTB-MD is an efficient but approximate method when dealing with strongly anharmonic systems, while path integral molecular dynamics (PIMD) gives exact results but in a huge amount of computation time. The QTB and PIMD methods have been combined in order to improve the PIMD convergence or correct the failures of the QTB-MD technique. Therefore, a new power spectral density of the random force within the QTB has been developed. A modified centroid-virial estimator of the kinetic energy, especially adapted to QTB-PIMD, has also been proposed. The method is applied to selected systems: a one-dimensional double-well system, a ferroelectric phase transition, and the position distribution of an hydrogen atom in a fuel cell material. The advantage of the QTB-PIMD method is its ability to give exact results with a more reasonable computation time for strongly anharmonic systems. PMID:26799437

  11. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  12. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    PubMed

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

    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

  15. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    PubMed Central

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  16. A method for assurance of image integrity in CAD-PACS integration

    NASA Astrophysics Data System (ADS)

    Zhou, Zheng

    2007-03-01

    Computer Aided Detection/Diagnosis (CAD) can greatly assist in the clinical decision making process, and therefore, has drawn tremendous research efforts. However, integrating independent CAD workstation results with the clinical diagnostic workflow still remains challenging. We have presented a CAD-PACS integration toolkit that complies with DICOM standard and IHE profiles. One major issue in CAD-PACS integration is the security of the images used in CAD post-processing and the corresponding CAD result images. In this paper, we present a method for assuring the integrity of both DICOM images used in CAD post-processing and the CAD image results that are in BMP or JPEG format. The method is evaluated in a PACS simulator that simulates clinical PACS workflow. It can also be applied to multiple CAD applications that are integrated with the PACS simulator. The successful development and evaluation of this method will provide a useful approach for assuring image integrity of the CAD-PACS integration in clinical diagnosis.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. A virtualized infrastructure for molecular imaging research using a data grid model

    NASA Astrophysics Data System (ADS)

    Lee, Jasper; Dagliyan, Grant; Liu, Brent

    2009-02-01

    The animal-to-researcher workflow in many of today's small animal imaging center is burdened with proprietary data limitations, inaccessible back-up methods, and imaging results that are not easily viewable across campus. Such challenges decrease the amount of scans performed per day at the center and requires researchers to wait longer for their images and quantified results. Furthermore, data mining at the small animal imaging center is often limited to researcher names and date-labelled archiving hard-drives. To gain efficiency and reliable access to small animal imaging data, such a center needs to move towards an integrated workflow with file format normalization services, metadata databases, expandable archiving infrastructure, and comprehensive user interfaces for query / retrieval tools - achieving all in a cost-effective manner. This poster presentation demonstrates how grid technology can support such a molecular imaging and small animal imaging research community to bridge the needs between imaging modalities and clinical researchers. Existing projects have utilized the Data Grid in PACS tier 2 backup solutions, where fault-tolerance is a high priority, as well as imagingbased clinical trials where data security and auditing are primary concerns. Issues to be addressed include, but are not limited to, novel database designs, file format standards, virtual archiving and distribution workflows, and potential grid computing for 3-D reconstructions, co-registration, and post-processing analysis.

  19. Deep-UV biological imaging by lanthanide ion molecular protection

    PubMed Central

    Kumamoto, Yasuaki; Fujita, Katsumasa; Smith, Nicholas Isaac; Kawata, Satoshi

    2015-01-01

    Deep-UV (DUV) light is a sensitive probe for biological molecules such as nucleobases and aromatic amino acids due to specific absorption. However, the use of DUV light for imaging is limited because DUV can destroy or denature target molecules in a sample. Here we show that trivalent ions in the lanthanide group can suppress molecular photodegradation under DUV exposure, enabling a high signal-to-noise ratio and repetitive DUV imaging of nucleobases in cells. Underlying mechanisms of the photodegradation suppression can be excitation relaxation of the DUV-absorptive molecules due to energy transfer to the lanthanide ions, and/or avoiding ionization and reactions with surrounding molecules, including generation of reactive oxygen species, which can modify molecules that are otherwise transparent to DUV light. This approach, directly removing excited energy at the fundamental origin of cellular photodegradation, indicates an important first step towards the practical use of DUV imaging in a variety of biological applications. PMID:26819825

  20. Bioconjugated Quantum Dots for In Vivo Molecular and Cellular Imaging

    PubMed Central

    Smith, Andrew M.; Duan, Hongwei; Mohs, Aaron M.; Nie, Shuming

    2008-01-01

    Semiconductor quantum dots (QDs) are tiny light-emitting particles on the nanometer scale, and are emerging as a new class of fluorescent labels for biology and medicine. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties, with size-tunable light emission, superior signal brightness, resistance to photobleaching, and broad absorption spectra for simultaneous excitation of multiple fluorescence colors. QDs also provide a versatile nanoscale scaffold for designing multifunctional nanoparticles with both imaging and therapeutic functions. When linked with targeting ligands such as antibodies, peptides or small molecules, QDs can be used to target tumor biomarkers as well as tumor vasculatures with high affinity and specificity. Here we discuss the synthesis and development of state-of-the-art QD probes and their use for molecular and cellular imaging. We also examine key issues for in vivo imaging and therapy, such as nanoparticle biodistribution, pharmacokinetics, and toxicology. PMID:18495291

  1. Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification.

    PubMed

    Toczek, Jakub; Meadows, Judith L; Sadeghi, Mehran M

    2016-01-01

    Selection of patients for abdominal aortic aneurysm repair is currently based on aneurysm size, growth rate, and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, for example, inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in abdominal aortic aneurysm morbidity and mortality. (18)F-fluorodeoxyglucose-positron emission tomography and ultrasmall superparamagnetic particles of iron oxide magnetic resonance imaging are 2 novel approaches to abdominal aortic aneurysm imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (eg, integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of abdominal aortic aneurysm and show great potential for clinical translation. PMID:26763279

  2. Deep-UV biological imaging by lanthanide ion molecular protection.

    PubMed

    Kumamoto, Yasuaki; Fujita, Katsumasa; Smith, Nicholas Isaac; Kawata, Satoshi

    2016-01-01

    Deep-UV (DUV) light is a sensitive probe for biological molecules such as nucleobases and aromatic amino acids due to specific absorption. However, the use of DUV light for imaging is limited because DUV can destroy or denature target molecules in a sample. Here we show that trivalent ions in the lanthanide group can suppress molecular photodegradation under DUV exposure, enabling a high signal-to-noise ratio and repetitive DUV imaging of nucleobases in cells. Underlying mechanisms of the photodegradation suppression can be excitation relaxation of the DUV-absorptive molecules due to energy transfer to the lanthanide ions, and/or avoiding ionization and reactions with surrounding molecules, including generation of reactive oxygen species, which can modify molecules that are otherwise transparent to DUV light. This approach, directly removing excited energy at the fundamental origin of cellular photodegradation, indicates an important first step towards the practical use of DUV imaging in a variety of biological applications. PMID:26819825

  3. A novel SPECT camera for molecular imaging of the prostate

    NASA Astrophysics Data System (ADS)

    Cebula, Alan; Gilland, David; Su, Li-Ming; Wagenaar, Douglas; Bahadori, Amir

    2011-10-01

    The objective of this work is to develop an improved SPECT camera for dedicated prostate imaging. Complementing the recent advancements in agents for molecular prostate imaging, this device has the potential to assist in distinguishing benign from aggressive cancers, to improve site-specific localization of cancer, to improve accuracy of needle-guided prostate biopsy of cancer sites, and to aid in focal therapy procedures such as cryotherapy and radiation. Theoretical calculations show that the spatial resolution/detection sensitivity of the proposed SPECT camera can rival or exceed 3D PET and further signal-to-noise advantage is attained with the better energy resolution of the CZT modules. Based on photon transport simulation studies, the system has a reconstructed spatial resolution of 4.8 mm with a sensitivity of 0.0001. Reconstruction of a simulated prostate distribution demonstrates the focal imaging capability of the system.

  4. Photoacoustic molecular imaging for in vivo liver iron quantitation

    NASA Astrophysics Data System (ADS)

    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.

  5. Lens customization method to minimize aberration in integral imaging

    NASA Astrophysics Data System (ADS)

    Miranda, Matheus; Kim, Jonghyun; Hong, Keehoon; Lee, Byoungho

    2015-10-01

    Conventionally the elemental lenses of the lens-array used in integral imaging have spherical surface profiles, thus they suffer from intrinsic lens aberrations such as spherical aberration and astigmatism. Aberrations affect the ability of the lens to focus light in a single point, or to collimate light from a point source. In integral imaging, this results in a loss of image quality of the reconstructed image due to distortions. The viewing characteristics of the integral imaging system, such as viewing angle and image resolution, are also affected by aberrations. We propose the use of a custom made aspherical lens-array which was specifically designed to minimize distortions due to aberrations and hence improve the reconstructed image quality. Ray optics calculations are used in order to analyze the aberrations and find the initial lens surface profile. Lens optimization is performed with the aid of numerical simulation software. The designed lens-array is compared to a conventional spherical lens-array of same properties. The design, optimization, and fabrication processes are described and the experiments are presented and compared with the computer simulations.

  6. Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging.

    PubMed

    Zhang, Jing

    2015-01-01

    Recent findings have led to a renewed interest and support for an active role of inflammation in neurodegenerative dementias and related neurologic disorders. Detection of neuroinflammation in vivo throughout the course of neurodegenerative diseases is of great clinical interest. Studies have shown that microglia activation (an indicator of neuroinflammation) may present at early stages of frontotemporal dementia (FTD), but the role of neuroinflammation in the pathogenesis of FTD is largely unknown. The first-generation translocator protein (TSPO) ligand ([(11)C]-PK11195) has been used to detect microglia activation in FTD, and the second-generation TSPO ligands have imaged neuroinflammation in vivo with improved pharmacokinetic properties. This paper reviews related literature and technical issues on mapping neuroinflammation in FTD with positron-emission tomography (PET) imaging. Early detection of neuroinflammation in FTD may identify new tools for diagnosis, novel treatment targets, and means to monitor therapeutic efficacy. More studies are needed to image and track neuroinflammation in FTD. It is anticipated that the advances of TSPO PET imaging will overcome technical difficulties, and molecular imaging of neuroinflammation will aid in the characterization of neuroinflammation in FTD. Such knowledge has the potential to shed light on the poorly understood pathogenesis of FTD and related dementias, and provide imaging markers to guide the development and assessment of new therapies. PMID:26022249

  7. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

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

    2016-01-01

    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 behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead 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 tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization 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. PMID:25693661

  8. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging

    PubMed Central

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E.; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  9. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging.

    PubMed

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von Zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  10. Therapeutic Evaluation of microRNAs by Molecular Imaging

    PubMed Central

    Sekar, Thillai V.; Mohanram, Ramkumar Kunga; Foygel, Kira; Paulmurugan, Ramasamy

    2013-01-01

    MicroRNAs (miRNAs) function as regulatory molecules of gene expression with multifaceted activities that exhibit direct or indirect oncogenic properties, which promote cell proliferation, differentiation, and the development of different types of cancers. Because of their extensive functional involvement in many cellular processes, under both normal and pathological conditions such as various cancers, this class of molecules holds particular interest for cancer research. MiRNAs possess the ability to act as tumor suppressors or oncogenes by regulating the expression of different apoptotic proteins, kinases, oncogenes, and other molecular mechanisms that can cause the onset of tumor development. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a large number of oncogenic factors, and therefore are anticipated to be highly efficacious. Given their unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics for a variety of cancers. More than thousand miRNAs have been identified to date, and their molecular mechanisms and functions are well studied. Furthermore, they are established as compelling therapeutic targets in a variety of cellular complications. However, the notion of using them as therapeutic tool was proposed only recently, given that modern imaging methods are just beginning to be deployed for miRNA research. In this review, we present a summary of various molecular imaging methods, which are instrumental in revealing the therapeutic potential of miRNAs, especially in various cancers. Imaging methods have recently been developed for monitoring the expression levels of miRNAs and their target genes by fluorescence-, bioluminescence- and chemiluminescence-based imaging techniques. Mature miRNAs bind to the untranslated regions (UTRs) of the target mRNAs and regulate target genes expressions. This concept has been used for the development of fluorescent reporter

  11. Note: Raman microspectroscopy integrated with fluorescence and dark field imaging

    NASA Astrophysics Data System (ADS)

    Li, Haibo; Wang, Hailong; Huang, Dianshuai; Liang, Lijia; Gu, Yuejiao; Liang, Chongyang; Xu, Shuping; Xu, Weiqing

    2014-05-01

    A Raman detection platform integrated with both fluorescence and dark field microscopes was built for in situ Raman detection with the assistance of fluorescence and dark field imaging to locate the target micro regions. Cells and organelles can be easily found via fluorescence imaging with labeling techniques. Besides, nano-sized particles could be observed and located by dark field microscopes. Therefore, comparing with the commercial Raman spectrometers, much more researches based on Raman spectroscopy could be carried out on this integrated Raman platform, especially in the fields of analyzing biological tissues and subwavelength samples.

  12. Integral imaging for anti-access/area denial environments

    NASA Astrophysics Data System (ADS)

    Chen, Kenny; Mahalanobis, Abhijit; Stanfill, Robert; Javidi, Bahram

    2015-05-01

    There is a growing interest in target detection and tracking in Anti-Access/Area Denial (A2AD) environments, where sensor platforms are at low altitudes and imagery are collected at oblique angles. Targets that are of interest in these scenarios are typically partially or mostly occluded by foliage or other objects. We present experiments to illustrate reconstruction of obscured targets using Integral Imaging, in both synthetically generated data and data collected using a multi-sensor system. We also explore the effects of Integral Imaging on Aided Target Recognition (AiTR), as well as performance improvement on target tracking.

  13. Integrating Radar Image Data with Google Maps

    NASA Technical Reports Server (NTRS)

    Chapman, Bruce D.; Gibas, Sarah

    2010-01-01

    A public Web site has been developed as a method for displaying the multitude of radar imagery collected by NASA s Airborne Synthetic Aperture Radar (AIRSAR) instrument during its 16-year mission. Utilizing NASA s internal AIRSAR site, the new Web site features more sophisticated visualization tools that enable the general public to have access to these images. The site was originally maintained at NASA on six computers: one that held the Oracle database, two that took care of the software for the interactive map, and three that were for the Web site itself. Several tasks were involved in moving this complicated setup to just one computer. First, the AIRSAR database was migrated from Oracle to MySQL. Then the back-end of the AIRSAR Web site was updated in order to access the MySQL database. To do this, a few of the scripts needed to be modified; specifically three Perl scripts that query that database. The database connections were then updated from Oracle to MySQL, numerous syntax errors were corrected, and a query was implemented that replaced one of the stored Oracle procedures. Lastly, the interactive map was designed, implemented, and tested so that users could easily browse and access the radar imagery through the Google Maps interface.

  14. Convexity properties of images under nonlinear integral operators

    SciTech Connect

    Kokurin, M Yu

    2014-12-31

    Conditions are obtained for the image of a given set under a general completely continuous nonlinear integral operator to have convex closure. These results are used to establish the uniqueness of quasi-solutions of nonlinear integral equations of the first kind and to prove the solvability of equations of the first kind on a dense subset of the right-hand sides. Bibliography: 11 titles.

  15. Portal dosimetry for VMAT using integrated images obtained during treatment

    SciTech Connect

    Bedford, James L. Hanson, Ian M.; Hansen, Vibeke Nordmark

    2014-02-15

    Purpose: Portal dosimetry provides an accurate and convenient means of verifying dose delivered to the patient. A simple method for carrying out portal dosimetry for volumetric modulated arc therapy (VMAT) is described, together with phantom measurements demonstrating the validity of the approach. Methods: Portal images were predicted by projecting dose in the isocentric plane through to the portal image plane, with exponential attenuation and convolution with a double-Gaussian scatter function. Appropriate parameters for the projection were selected by fitting the calculation model to portal images measured on an iViewGT portal imager (Elekta AB, Stockholm, Sweden) for a variety of phantom thicknesses and field sizes. This model was then used to predict the portal image resulting from each control point of a VMAT arc. Finally, all these control point images were summed to predict the overall integrated portal image for the whole arc. The calculated and measured integrated portal images were compared for three lung and three esophagus plans delivered to a thorax phantom, and three prostate plans delivered to a homogeneous phantom, using a gamma index for 3% and 3 mm. A 0.6 cm{sup 3} ionization chamber was used to verify the planned isocentric dose. The sensitivity of this method to errors in monitor units, field shaping, gantry angle, and phantom position was also evaluated by means of computer simulations. Results: The calculation model for portal dose prediction was able to accurately compute the portal images due to simple square fields delivered to solid water phantoms. The integrated images of VMAT treatments delivered to phantoms were also correctly predicted by the method. The proportion of the images with a gamma index of less than unity was 93.7% ± 3.0% (1SD) and the difference between isocenter dose calculated by the planning system and measured by the ionization chamber was 0.8% ± 1.0%. The method was highly sensitive to errors in monitor units and

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

    PubMed

    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

  17. Molecular magnetic resonance imaging of brain–immune interactions

    PubMed Central

    Gauberti, Maxime; Montagne, Axel; Quenault, Aurélien; Vivien, Denis

    2014-01-01

    Although the blood–brain barrier (BBB) was thought to protect the brain from the effects of the immune system, immune cells can nevertheless migrate from the blood to the brain, either as a cause or as a consequence of central nervous system (CNS) diseases, thus contributing to their evolution and outcome. Accordingly, as the interface between the CNS and the peripheral immune system, the BBB is critical during neuroinflammatory processes. In particular, endothelial cells are involved in the brain response to systemic or local inflammatory stimuli by regulating the cellular movement between the circulation and the brain parenchyma. While neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted and resolved, cellular mechanisms of neuroinflammation are probably similar. Accordingly, neuroinflammation is a hallmark and a decisive player of many CNS diseases. Thus, molecular magnetic resonance imaging (MRI) of inflammatory processes is a central theme of research in several neurological disorders focusing on a set of molecules expressed by endothelial cells, such as adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin, …), which emerge as therapeutic targets and biomarkers for neurological diseases. In this review, we will present the most recent advances in the field of preclinical molecular MRI. Moreover, we will discuss the possible translation of molecular MRI to the clinical setting with a particular emphasis on myeloperoxidase imaging, autologous cell tracking, and targeted iron oxide particles (USPIO, MPIO). PMID:25505871

  18. Integrating medical imaging analyses through a high-throughput bundled resource imaging system

    NASA Astrophysics Data System (ADS)

    Covington, Kelsie; Welch, E. Brian; Jeong, Ha-Kyu; Landman, Bennett A.

    2011-03-01

    Exploitation of advanced, PACS-centric image analysis and interpretation pipelines provides well-developed storage, retrieval, and archival capabilities along with state-of-the-art data providence, visualization, and clinical collaboration technologies. However, pursuit of integrated medical imaging analysis through a PACS environment can be limiting in terms of the overhead required to validate, evaluate and integrate emerging research technologies. Herein, we address this challenge through presentation of a high-throughput bundled resource imaging system (HUBRIS) as an extension to the Philips Research Imaging Development Environment (PRIDE). HUBRIS enables PACS-connected medical imaging equipment to invoke tools provided by the Java Imaging Science Toolkit (JIST) so that a medical imaging platform (e.g., a magnetic resonance imaging scanner) can pass images and parameters to a server, which communicates with a grid computing facility to invoke the selected algorithms. Generated images are passed back to the server and subsequently to the imaging platform from which the images can be sent to a PACS. JIST makes use of an open application program interface layer so that research technologies can be implemented in any language capable of communicating through a system shell environment (e.g., Matlab, Java, C/C++, Perl, LISP, etc.). As demonstrated in this proof-of-concept approach, HUBRIS enables evaluation and analysis of emerging technologies within well-developed PACS systems with minimal adaptation of research software, which simplifies evaluation of new technologies in clinical research and provides a more convenient use of PACS technology by imaging scientists.

  19. Proposal for DICOM multiframe medical image integrity and authenticity.

    PubMed

    Kobayashi, Luiz O M; Furuie, Sergio S

    2009-03-01

    This paper presents a novel algorithm to successfully achieve viable integrity and authenticity addition and verification of n-frame DICOM medical images using cryptographic mechanisms. The aim of this work is the enhancement of DICOM security measures, especially for multiframe images. Current approaches have limitations that should be properly addressed for improved security. The algorithm proposed in this work uses data encryption to provide integrity and authenticity, along with digital signature. Relevant header data and digital signature are used as inputs to cipher the image. Therefore, one can only retrieve the original data if and only if the images and the inputs are correct. The encryption process itself is a cascading scheme, where a frame is ciphered with data related to the previous frames, generating also additional data on image integrity and authenticity. Decryption is similar to encryption, featuring also the standard security verification of the image. The implementation was done in JAVA, and a performance evaluation was carried out comparing the speed of the algorithm with other existing approaches. The evaluation showed a good performance of the algorithm, which is an encouraging result to use it in a real environment. PMID:18266035

  20. Photoacoustic molecular imaging of ferritin as a reporter gene

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

    Spectral analysis of photoacoustic (PA) molecular imaging (PMI) of ferritin expressed in human melanoma cells (SK-24) was performed in vitro. Ferritin is a ubiquitously expressed protein which stores iron that can be detected by PA imaging, allowing ferritin to act as a reporter gene. To over-express ferritin, SK-24 cells were co-transfected with plasmid expressing Heavy chain ferritin (H-FT) and plasmid expressing enhanced green fluorescent protein (pEGFP-C1) using LipofectamineTM 2000. Non-transfected SK-24 cells served as a negative control. Fluorescent imaging of EGFP confirmed transfection and transgene expression in co-transfected cells. To detect iron accumulation in SK-24 cells, a focused high frequency ultrasonic transducer (60 MHz, f/1.5), synchronized to a pulsed laser (<20mJ/cm2), was used to scan the PA signal from 680 nm to 950 nm (in 10 nm increments) from the surface of the 6-well culturing plate. PA signal intensity from H-FT transfected SK-24 cells was not different from that of non-transfected SK-24 cells at wavelengths less than 770 nm, but was over 4 dB higher than non-transfected SK-24 cells at 850 ~ 950 nm. Fluorescent microscopy indicates significant accumulation of ferritin in H-FT transfected SK-24 cells, with little ferritin expression in non-transfected SK-24 cells. The PA spectral analysis clearly differentiates transfected SK-24 cells from nontransfected SK-24 cells with significantly increased iron signal at 850 ~ 950 nm, and these increased signals were associated with transfection of H-FT plasmid. As such, the feasibility of ferritin as a reporter gene for PMI has been demonstrated in vitro. The use of ferritin as a reporter gene represents a new concept for PA imaging, and may provide various opportunities for molecular imaging and basic science research.

  1. A targeted molecular probe for colorectal cancer imaging

    NASA Astrophysics Data System (ADS)

    Attramadal, T.; Bjerke, R.; Indrevoll, B.; Moestue, S.; Rogstad, A.; Bendiksen, R.; Healey, A.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

  2. A molecular image-directed, 3D ultrasound-guided biopsy system for the prostate

    NASA Astrophysics Data System (ADS)

    Fei, Baowei; Schuster, David M.; Master, Viraj; Akbari, Hamed; Fenster, Aaron; Nieh, Peter

    2012-02-01

    Systematic transrectal ultrasound (TRUS)-guided biopsy is the standard method for a definitive diagnosis of prostate cancer. However, this biopsy approach uses two-dimensional (2D) ultrasound images to guide biopsy and can miss up to 30% of prostate cancers. We are developing a molecular image-directed, three-dimensional (3D) ultrasound imageguided biopsy system for improved detection of prostate cancer. The system consists of a 3D mechanical localization system and software workstation for image segmentation, registration, and biopsy planning. In order to plan biopsy in a 3D prostate, we developed an automatic segmentation method based wavelet transform. In order to incorporate PET/CT images into ultrasound-guided biopsy, we developed image registration methods to fuse TRUS and PET/CT images. The segmentation method was tested in ten patients with a DICE overlap ratio of 92.4% +/- 1.1 %. The registration method has been tested in phantoms. The biopsy system was tested in prostate phantoms and 3D ultrasound images were acquired from two human patients. We are integrating the system for PET/CT directed, 3D ultrasound-guided, targeted biopsy in human patients.

  3. Renal masses in children. An integrated imaging approach to diagnosis

    SciTech Connect

    Wolfson, B.J.; Gainey, M.A.; Faerber, E.N.; Capitanio, M.A.

    1985-11-01

    In view of the continuing technologic advancements in the development and availability of diagnostic imaging modalities, it is appropriate to assess periodically the currently accepted approaches to the evaluation of renal masses in children. The roles, advantages, and disadvantages of plain film, intravenous urography, ultrasonography, radionuclide scintigraphy, computed tomography, angiography, and magnetic resonance imaging in the approach to the evaluation of renal masses in children are discussed. An integrated imaging approach that provides the most accurate and necessary information for diagnosis and treatment is recommended. 70 references.

  4. Imaging using parallel integrals in optical projection tomography

    NASA Astrophysics Data System (ADS)

    Wang, Yi; Wang, Ruikang

    2006-12-01

    We develop and demonstrate improved image-forming optics for optical projection tomography (OPT), with which the parallel integral throughout an object can be obtained. This method results in an improved resolution for OPT images, especially for the cross sections far from the optical axis of the image-forming optics. We find the optimal configuration used in our OPT system by use of a point spread function and simulation technique. The new method is validated by both numerical simulations and experimental results. The spatial resolution of the OPT system presented is ~40 µm.

  5. Snapshot imaging of postpulse transient molecular alignment revivals

    NASA Astrophysics Data System (ADS)

    Loriot, V.; Tehini, R.; Hertz, E.; Lavorel, B.; Faucher, O.

    2008-07-01

    Laser induced field-free alignment of linear molecules is investigated by using a single-shot spatial imaging technique. The measurements are achieved by femtosecond time-resolved optical polarigraphy (FTOP). Individual alignment revivals recorded at high resolution in CO2 , as well as simultaneous observation of several alignment revivals produced within the rotational period of the O2 molecule are reported. The data are analyzed with a theoretical model describing the alignment experienced by each molecule standing within the interaction region observed by the detector. The temporal dynamics, intensity dependence, and degree of alignment are measured and compared with the awaited results. The technique is simple and can be easily implemented in a large class of molecular samples. Improvement to extend the performance of the method is discussed. The reported study is a decisive step toward feedback optimization and optimal control of field-free molecular alignment.

  6. Optimal flushing agents for integrated optical and acoustic imaging systems

    PubMed Central

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, Kirk; Zhou, Qifa; Patel, Pranav; Chen, Zhongping

    2015-01-01

    Abstract. An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging. PMID:25985096

  7. Optimal flushing agents for integrated optical and acoustic imaging systems.

    PubMed

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, Kirk; Zhou, Qifa; Patel, Pranav; Chen, Zhongping

    2015-05-01

    An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging. PMID:25985096

  8. Optimal flushing agents for integrated optical and acoustic imaging systems

    NASA Astrophysics Data System (ADS)

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, Kirk; Zhou, Qifa; Patel, Pranav; Chen, Zhongping

    2015-05-01

    An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging.

  9. Photoacoustic section imaging with an integrating cylindrical detector

    NASA Astrophysics Data System (ADS)

    Gratt, Sibylle; Passler, Klaus; Nuster, Robert; Paltauf, Guenther

    2011-07-01

    A piezoelectric detector with cylindrical shape for photoacoustic section imaging is characterized. This detector is larger than the imaging object in direction of the cylinder axis, giving rise to its integrating properties. Its focal volume has the shape of a slice and the acquisition of signals for one section image requires rotation of an object about an axis perpendicular to this slice. Image reconstruction from the signals requires the application of the inverse Radon transform. It is shown that implementing the Abel transform is a suitable step in data processing, allowing speeding up the data acquisition since the scanning angle can be reduced. The resolution of the detector was estimated in directions perpendicular and parallel to the detection plane. An upper limit for the out of plane resolution is given and section images of a zebra fish are shown.

  10. Luminescent Nanomaterials for Molecular-Specific Cellular Imaging

    NASA Astrophysics Data System (ADS)

    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

  11. Analytical models integrated with satellite images for optimized pest management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The global field protection (GFP) was developed to protect and optimize pest management resources integrating satellite images for precise field demarcation with physical models of controlled release devices of pesticides to protect large fields. The GFP was implemented using a graphical user interf...

  12. Integrated text detection and recognition in natural images

    NASA Astrophysics Data System (ADS)

    Roubtsova, Nadejda S.; Wijnhoven, Rob G. J.; de With, Peter H. N.

    2012-03-01

    Text detection and recognition in natural images have conventionally been seen in the prior art as autonomous tasks executed in a strictly sequential processing chain with limited information sharing between sub-systems. This approach is flawed because it introduces (1) redundancy in extracting the same text properties multiple times and (2) error by prohibiting verification of hard (often binarized) detection results at later stages. We explore the possibilities for integration of detection and recognition modules by a feedforward multidimensional information stream. Integration involves suitable characterization of the text string at detection and application of the knowledge to ease recognition by a given OCR system. The choice of characterization properties generally depends on the OCR system, although some of them have proven universally applicable. We show that the proposed integration measures enable more robust recognition of text in complex, unconstrained natural environments. Specifically, integration by the proposed measures (1) eliminates textual input irregularities that recognition engines cannot handle and (2) adaptively tunes the recognition stage for each input image. The former function boosts correct detections, while the latter mainly reduces the number of false positives. Our validation experiments on a set of low-quality natural images show that adaptively tuning the OCR stage to the typical text-to-background transitions in the input image (gradient significance profiling) allows to attain an improvement of 29% in the precision-recall performance, mostly through boosting precision.

  13. Using Digital Images with Young Children: Challenges of Integration

    ERIC Educational Resources Information Center

    Schiller, John; Tillett, Beryl

    2004-01-01

    In what ways can information and communications technologies (ICT) be integrated into classroom practice to create a 'community of learners'? This paper describes an action research project, over a six-month period, in which a class of seven-year-old and eight-year-old children in a metropolitan South Australian school created digital images to…

  14. Integrated Optics for Planar imaging and Optical Signal Processing

    NASA Astrophysics Data System (ADS)

    Song, Qi

    Silicon photonics is a subject of growing interest with the potential of delivering planar electro-optical devices with chip scale integration. Silicon-on-insulator (SOI) technology has provided a marvelous platform for photonics industry because of its advantages in integration capability in CMOS circuit and countless nonlinearity applications in optical signal processing. This thesis is focused on the investigation of planar imaging techniques on SOI platform and potential applications in ultra-fast optical signal processing. In the first part, a general review and background introduction about integrated photonics circuit and planar imaging technique are provided. In chapter 2, planar imaging platform is realized by a silicon photodiode on SOI chip. Silicon photodiode on waveguide provides a high numerical aperture for an imaging transceiver pixel. An erbium doped Y2O3 particle is excited by 1550nm Laser and the fluorescent image is obtained with assistance of the scanning system. Fluorescence image is reconstructed by using image de-convolution technique. Under photovoltaic mode, we use an on-chip photodiode and an external PIN photodiode to realize similar resolution as 5μm. In chapter 3, a time stretching technique is developed to a spatial domain to realize a 2D imaging system as an ultrafast imaging tool. The system is evaluated based on theoretical calculation. The experimental results are shown for a verification of system capability to imaging a micron size particle or a finger print. Meanwhile, dynamic information for a moving object is also achieved by correlation algorithm. In chapter 4, the optical leaky wave antenna based on SOI waveguide has been utilized for imaging applications and extensive numerical studied has been conducted. and the theoretical explanation is supported by leaky wave theory. The highly directive radiation has been obtained from the broadside with 15.7 dB directivity and a 3dB beam width of ΔØ 3dB ≈ 1.65° in free space

  15. Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

    PubMed

    Dweck, Marc R; Aikawa, Elena; Newby, David E; Tarkin, Jason M; Rudd, James H F; Narula, Jagat; Fayad, Zahi A

    2016-07-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID:27390335

  16. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    NASA Astrophysics Data System (ADS)

    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.

  17. Multifunctional gold nanostars for molecular imaging and cancer therapy

    PubMed Central

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

    2015-01-01

    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 (PDT). 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. PMID:26322306

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

    PubMed Central

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

    2013-01-01

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

  19. The Imaging Probe Development Center and the Production of Molecular Imaging Probes

    PubMed Central

    Griffiths, Gary L

    2008-01-01

    The Imaging Probe Development Center (IPDC), part of the NIH Roadmap for Medical Research Initiative (http://nihroadmap.nih.gov/) recently became fully operational at its newly refurbished laboratories in Rockville, MD. The IPDC (http://nihroadmap.nih.gov/molecularlibraries/ipdc/) is dedicated to the production of known and novel molecular imaging probes, with its services currently being used by the NIH intramural community, although in the future it is intended that the extramural community will also benefit from the IPDC’s resources. The Center has been set up with the belief that molecular imaging, and the probe chemistry that underpins it, will constitute key technologies going forward. As part of the larger molecular libraries and imaging initiative, it is planned that the IPDC will work closely with scientists from the molecular libraries effort. Probes produced at the IPDC include optical, radionuclide and magnetic resonance agents and may encompass any type of contrast agent. As IPDC is a trans-NIH resource it can serve each of the 27 Institutes and Centers that comprise NIH so its influence can be expected to impact widely different subjects and disease conditions spanning biological research. IPDC is expected to play a key part in interdisciplinary collaborative imaging projects and to support translational R&D from basic research through clinical development, for all of the imaging modalities. Examples of probes already prepared or under preparation are outlined to illustrate the breadth of the chemistries undertaken together with a reference outline of the diverse biological applications for which the various probes are intended. PMID:20161829

  20. Radionuclide imaging - A molecular key to the atherosclerotic plaque

    PubMed Central

    Langer, Harald Franz; Haubner, Roland; Pichler, Bernd Juergen; Gawaz, Meinrad

    2008-01-01

    Despite primary and secondary prevention, serious cardiovascular events like unstable angina or myocardial infarction still account for one third of all deaths worldwide. Therefore, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in cardiovascular medicine. Several non-invasive techniques, such as MRI, multislice computed tomography and electron beam tomography are currently being tested for their ability to identify such patients by morphological criteria. In contrast, molecular imaging techniques use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing its biological activity. Based upon the knowledge about the pathophysiology of atherosclerosis, various studies in vitro, in vivo and the first clinical trials have used different tracers for plaque imaging studies, including radioactive labelled lipoproteins, components of the coagulation system, cytokines, mediators of the metalloproteinase system, cell adhesion receptors and even whole cells. This review gives an update on the relevant non-invasive plaque imaging approaches using nuclear imaging techniques to detect atherosclerotic vascular lesions. PMID:18582628

  1. Tumor Functional and Molecular Imaging Utilizing Ultrasound and Ultrasound-Mediated Optical Techniques

    PubMed Central

    Yuan, Baohong; Rychak, Joshua

    2014-01-01

    Tumor functional and molecular imaging has significantly contributed to cancer preclinical research and clinical applications. Among typical imaging modalities, ultrasonic and optical techniques are two commonly used methods; both share several common features such as cost efficiency, absence of ionizing radiation, relatively inexpensive contrast agents, and comparable maximum-imaging depth. Ultrasonic and optical techniques are also complementary in imaging resolution, molecular sensitivity, and imaging space (vascular and extravascular). The marriage between ultrasonic and optical techniques takes advantages of both techniques. This review introduces tumor functional and molecular imaging using microbubble-based ultrasound and ultrasound-mediated optical imaging techniques. PMID:23219728

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

    PubMed Central

    Klibanov, Alexander L.; Hossack, John A.

    2015-01-01

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

  3. Integrating a FISH imaging system into the cytology laboratory

    PubMed Central

    Smith, G. Denice; Riding, Matt; Oswald, Kim

    2010-01-01

    We have implemented an interactive imaging system for the interpretation of UroVysion fluorescence in situ hybridization (FISH) to improve throughput, productivity, quality control and diagnostic accuracy. We describe the Duet imaging system, our experiences with implementation, and outline the financial investment, space requirements, information technology needs, validation, and training of cytotechnologists needed to integrate such a system into a cytology laboratory. Before purchasing the imaging system, we evaluated and validated the instrument at our facility. Implementation required slide preparation changes, IT modifications, development of training programs, and revision of job descriptions for cytotechnologists. A darkened room was built to house the automated scanning station and microscope, as well as two imaging stations. IT changes included generation of storage for archival images on the LAN, addition of external hard drives for back-up, and changes to cable connections for communication between remote locations. Training programs for cytotechnologists, and pathologists/fellows/residents were developed, and cytotechnologists were integrated into multiple steps of the process. The imaging system has resulted in increased productivity for pathologists, concomitant with an expanded role of cytotechnologists in multiple critical steps, including FISH, scan setup, reclassification, and initial interpretation. PMID:20436794

  4. Integrated optical 3D digital imaging based on DSP scheme

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Peng, Xiang; Gao, Bruce Z.

    2008-03-01

    We present a scheme of integrated optical 3-D digital imaging (IO3DI) based on digital signal processor (DSP), which can acquire range images independently without PC support. This scheme is based on a parallel hardware structure with aid of DSP and field programmable gate array (FPGA) to realize 3-D imaging. In this integrated scheme of 3-D imaging, the phase measurement profilometry is adopted. To realize the pipeline processing of the fringe projection, image acquisition and fringe pattern analysis, we present a multi-threads application program that is developed under the environment of DSP/BIOS RTOS (real-time operating system). Since RTOS provides a preemptive kernel and powerful configuration tool, with which we are able to achieve a real-time scheduling and synchronization. To accelerate automatic fringe analysis and phase unwrapping, we make use of the technique of software optimization. The proposed scheme can reach a performance of 39.5 f/s (frames per second), so it may well fit into real-time fringe-pattern analysis and can implement fast 3-D imaging. Experiment results are also presented to show the validity of proposed scheme.

  5. Integrating a FISH imaging system into the cytology laboratory.

    PubMed

    Smith, G Denice; Riding, Matt; Oswald, Kim; Bentz, Joel S

    2010-01-01

    We have implemented an interactive imaging system for the interpretation of UroVysion fluorescence in situ hybridization (FISH) to improve throughput, productivity, quality control and diagnostic accuracy. We describe the Duet imaging system, our experiences with implementation, and outline the financial investment, space requirements, information technology needs, validation, and training of cytotechnologists needed to integrate such a system into a cytology laboratory. Before purchasing the imaging system, we evaluated and validated the instrument at our facility. Implementation required slide preparation changes, IT modifications, development of training programs, and revision of job descriptions for cytotechnologists. A darkened room was built to house the automated scanning station and microscope, as well as two imaging stations. IT changes included generation of storage for archival images on the LAN, addition of external hard drives for back-up, and changes to cable connections for communication between remote locations. Training programs for cytotechnologists, and pathologists/fellows/residents were developed, and cytotechnologists were integrated into multiple steps of the process. The imaging system has resulted in increased productivity for pathologists, concomitant with an expanded role of cytotechnologists in multiple critical steps, including FISH, scan setup, reclassification, and initial interpretation. PMID:20436794

  6. Integrated ultrasound and gamma imaging probe for medical diagnosis

    NASA Astrophysics Data System (ADS)

    Pani, R.; Pellegrini, R.; Cinti, M. N.; Polito, C.; Orlandi, C.; Fabbri, A.; De Vincentis, G.

    2016-03-01

    In the last few years, integrated multi-modality systems have been developed, aimed at improving the accuracy of medical diagnosis correlating information from different imaging techniques. In this contest, a novel dual modality probe is proposed, based on an ultrasound detector integrated with a small field of view single photon emission gamma camera. The probe, dedicated to visualize small organs or tissues located at short depths, performs dual modality images and permits to correlate morphological and functional information. The small field of view gamma camera consists of a continuous NaI:Tl scintillation crystal coupled with two multi-anode photomultiplier tubes. Both detectors were characterized in terms of position linearity and spatial resolution performances in order to guarantee the spatial correspondence between the ultrasound and the gamma images. Finally, dual-modality images of custom phantoms are obtained highlighting the good co-registration between ultrasound and gamma images, in terms of geometry and image processing, as a consequence of calibration procedures.

  7. Behavioral, molecular and integrative mechanisms of amphibian osmoregulation.

    PubMed

    Hillyard, S D

    1999-06-01

    Amphibian water balance has been studied at many levels of biological order. Terrestrial species must react to environmental cues that relate to water availability while some arboreal species have cutaneous skin secretions that can reduce evaporative water loss. The Indian tree frog. Polypedates maculatus, uses cutaneous secretions and wiping behavior to lower evaporation but also relies on moist microclimates to endure prolonged survival away from water. The related species, P. leucomystax, inhabits wetter forest habitats. Preliminary studies with this species are unable to demonstrate the expression of wiping behavior, indicating that arid habitats may be a powerful selective force for this behavior. Laboratory experiments on rehydrating toads in the genus Bufo indicate that animals are able to detect changes in barometric pressure and humidity that might result in the availability of water under field situations. Experiments with Bufonid species and with spadefoot toads, Scaphiopus couchi, show that the peptide hormone, angiotensin II, stimulates cutaneous drinking in a similar manner seen for oral drinking by other vertebrate classes. Amphibian tissues have long been used as a model for the study of basic physiological principles of epithelial ion and water transport. Recent progress with tissue cultures has provided information on the molecular structure of ion and water channels that can be applied to obtain a better understanding, at the molecular level, of ion and water balance strategies used by the wide variety of amphibian species. Terrestrial amphibians are more tolerant of dehydration than are other vertebrates and are able to store dilute urine in their urinary bladder. Toads appear to be able to detect the presence of water in their bladders in addition to the availability of water in their environment. Dehydrated toads are able to rehydrate very rapidly by the coordination of behavioral and physiological mechanisms to enhance cutaneous water

  8. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    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

  9. A framework for integration of heterogeneous medical imaging networks.

    PubMed

    Viana-Ferreira, Carlos; Ribeiro, Luís S; Costa, Carlos

    2014-01-01

    Medical imaging is increasing its importance in matters of medical diagnosis and in treatment support. Much is due to computers that have revolutionized medical imaging not only in acquisition process but also in the way it is visualized, stored, exchanged and managed. Picture Archiving and Communication Systems (PACS) is an example of how medical imaging takes advantage of computers. To solve problems of interoperability of PACS and medical imaging equipment, the Digital Imaging and Communications in Medicine (DICOM) standard was defined and widely implemented in current solutions. More recently, the need to exchange medical data between distinct institutions resulted in Integrating the Healthcare Enterprise (IHE) initiative that contains a content profile especially conceived for medical imaging exchange: Cross Enterprise Document Sharing for imaging (XDS-i). Moreover, due to application requirements, many solutions developed private networks to support their services. For instance, some applications support enhanced query and retrieve over DICOM objects metadata. This paper proposes anintegration framework to medical imaging networks that provides protocols interoperability and data federation services. It is an extensible plugin system that supports standard approaches (DICOM and XDS-I), but is also capable of supporting private protocols. The framework is being used in the Dicoogle Open Source PACS. PMID:25279021

  10. A Framework for Integration of Heterogeneous Medical Imaging Networks

    PubMed Central

    Viana-Ferreira, Carlos; Ribeiro, Luís S; Costa, Carlos

    2014-01-01

    Medical imaging is increasing its importance in matters of medical diagnosis and in treatment support. Much is due to computers that have revolutionized medical imaging not only in acquisition process but also in the way it is visualized, stored, exchanged and managed. Picture Archiving and Communication Systems (PACS) is an example of how medical imaging takes advantage of computers. To solve problems of interoperability of PACS and medical imaging equipment, the Digital Imaging and Communications in Medicine (DICOM) standard was defined and widely implemented in current solutions. More recently, the need to exchange medical data between distinct institutions resulted in Integrating the Healthcare Enterprise (IHE) initiative that contains a content profile especially conceived for medical imaging exchange: Cross Enterprise Document Sharing for imaging (XDS-i). Moreover, due to application requirements, many solutions developed private networks to support their services. For instance, some applications support enhanced query and retrieve over DICOM objects metadata. This paper proposes anintegration framework to medical imaging networks that provides protocols interoperability and data federation services. It is an extensible plugin system that supports standard approaches (DICOM and XDS-I), but is also capable of supporting private protocols. The framework is being used in the Dicoogle Open Source PACS. PMID:25279021

  11. Development of a calcium-sensing receptor molecular imaging agent

    PubMed Central

    Yusof, Adlina Mohd; Kothandaraman, Shankaran; Zhang, Xiaoli; Saji, Motoyasu; Ringel, Matthew D.; Tweedle, Michael F.; Phay, John E.

    2015-01-01

    Background Calcium-sensing receptor (CaSR) is expressed by parathyroid cells and thyroid C-cells (from which medullary thyroid carcinoma [MTC] is derived). A molecular imaging agent localizing to the CaSR could improve the detection of parathyroids and MTC preoperatively or intraoperatively. We synthesized a novel compound containing a fluorine residue for potential future labeling and demonstrated that the compound inhibited CaSR function in vitro. Methods We synthesized compound M, a derivative of a known calcilytic compound, Calhex-231. Human embryonic kidney cells transfected with green-fluorescent protein-tagged CaSR or control vector were preincubated with compound M before the addition of calcium. Immunoblotting for total mitogen-activated protein kinase (MAPK: ERK1/2), activated MAPK (phosphorylated ERK1/2), and glyceraldehyde 3-phosphate dehydrogenase was performed. Results Synthesis of compound M was confirmed by mass spectrometry. Inhibition of the MAPK signaling pathway by compound M was demonstrated in a dose-dependent manner by a decrease in phosphorylated ERK1/2 with no change in total ERK1/2 levels. Compound M inhibited MAPK signaling slightly better than the parent compound. Conclusion We have developed a novel molecule which demonstrates functional inhibition of CaSR and has a favorable structure for labeling. This compound appears to be appropriate for further development as a molecular imaging tool to enhance the surgical treatment of parathyroid disease and MTC. PMID:24238055

  12. Size-Minimized Quantum Dots for Molecular and Cellular Imaging

    NASA Astrophysics Data System (ADS)

    Smith, Andrew M.; Wen, Mary M.; Wang, May D.; Nie, Shuming

    Semiconductor quantum dots, tiny light-emitting particles on thenanometer scale, are emerging as a new class of fluorescent labels for a broad range of molecular and cellular applications. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties such as size-tunable light emission, intense signal brightness, resistance to photobleaching, and broadband absorption for simultaneous excitation of multiple fluorescence colors. Here we report new advances in minimizing the hydrodynamic sizes of quantum dots using multidentate and multifunctional polymer coatings. A key finding is that a linear polymer containing grafted amine and thiol coordinating groups can coat nanocrystals and lead to a highly compact size, exceptional colloidal stability, strong resistance to photobleaching, and high fluorescence quantum yields. This has allowed a new generation of bright and stable quantum dots with small hydrodynamic diameters between 5.6 and 9.7 nm with tunable fluorescence emission from the visible (515 nm) to the near infrared (720 nm). These quantum dots are well suited for molecular and cellular imaging applications in which the nanoparticle hydrodynamic size needs to be minimized. Together with the novel properties of new strain-tunable quantum dots, these findings will be especially useful for multicolor and super-resolution imaging at the single-molecule level.

  13. Raman molecular imaging of brain frozen tissue sections.

    PubMed

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins. PMID:25038847

  14. Towards imaging of ultrafast molecular dynamics using FELs

    NASA Astrophysics Data System (ADS)

    Rouzée, A.; Johnsson, P.; Rading, L.; Hundertmark, A.; Siu, W.; Huismans, Y.; Düsterer, S.; Redlin, H.; Tavella, F.; Stojanovic, N.; Al-Shemmary, A.; Lépine, F.; Holland, D. M. P.; Schlatholter, T.; Hoekstra, R.; Fukuzawa, H.; Ueda, K.; Vrakking, M. J. J.

    2013-08-01

    The dissociation dynamics induced by a 100 fs, 400 nm laser pulse in a rotationally cold Br2 sample was characterized by Coulomb explosion imaging (CEI) using a time-delayed extreme ultra-violet (XUV) FEL pulse, obtained from the Free electron LASer in Hamburg (FLASH). The momentum distribution of atomic fragments resulting from the 400 nm-induced dissociation was measured with a velocity map imaging spectrometer and used to monitor the internuclear distance as the molecule dissociated. By employing the simultaneously recorded in-house timing electro-optical sampling data, the time resolution of the final results could be improved to 300 fs, compared to the inherent 500 fs time-jitter of the FEL pulse. Before dissociation, the Br2 molecules were transiently ‘fixed in space’ using laser-induced alignment. In addition, similar alignment techniques were used on CO2 molecules to allow the measurement of the photoelectron angular distribution (PAD) directly in the molecular frame (MF). Our results on MFPADs in aligned CO2 molecules, together with our investigation of the dissociation dynamics of the Br2 molecules with CEI, show that information about the evolving molecular structure and electronic geometry can be retrieved from such experiments, therefore paving the way towards the study of complex non-adiabatic dynamics in molecules through XUV time-resolved photoion and photoelectron spectroscopy.

  15. Imaging HIV-1 nuclear pre-integration complexes.

    PubMed

    Cereseto, Anna; Giacca, Mauro

    2014-01-01

    Advancements in fluorescent microscopy techniques now permit investigation of HIV-1 biology exploiting tools alternative to conventional molecular biology. Here we describe a novel, fluorescence-based method to visualize HIV-1 viral particles within intact nuclei of infected cells. This method allows investigating the localization of pre-integration complexes within the nuclear compartment with respect to the nuclear envelope and the chromatin territories. PMID:24158813

  16. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

    1995-01-01

    In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

  17. Beating heart mitral valve repair with integrated ultrasound imaging

    NASA Astrophysics Data System (ADS)

    McLeod, A. Jonathan; Moore, John T.; Peters, Terry M.

    2015-03-01

    Beating heart valve therapies rely extensively on image guidance to treat patients who would be considered inoperable with conventional surgery. Mitral valve repair techniques including the MitrClip, NeoChord, and emerging transcatheter mitral valve replacement techniques rely on transesophageal echocardiography for guidance. These images are often difficult to interpret as the tool will cause shadowing artifacts that occlude tissue near the target site. Here, we integrate ultrasound imaging directly into the NeoChord device. This provides an unobstructed imaging plane that can visualize the valve lea ets as they are engaged by the device and can aid in achieving both a proper bite and spacing between the neochordae implants. A proof of concept user study in a phantom environment is performed to provide a proof of concept for this device.

  18. Ideal flushing agents for integrated optical acoustic imaging systems

    NASA Astrophysics Data System (ADS)

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, K. Kirk; Zhou, Qifa; Patel, Pranav M.; Chen, Zhongping

    2015-02-01

    An increased number of integrated optical acoustic intravascular imaging systems have been researched and hold great hope for accurate diagnosing of vulnerable plaques and for guiding atherosclerosis treatment. However, in any intravascular environment, vascular lumen is filled with blood, which is a high-scattering source for optical and high frequency ultrasound signals. Blood must be flushed away to make images clear. To our knowledge, no research has been performed to find the ideal flushing agent that works for both optical and acoustic imaging techniques. We selected three solutions, mannitol, dextran and iohexol, as flushing agents because of their image-enhancing effects and low toxicities. Quantitative testing of these flushing agents was performed in a closed loop circulation model and in vivo on rabbits.

  19. Synergistic Integration Of Heuristic Reasoning In Image Understanding Systems

    NASA Astrophysics Data System (ADS)

    Gilmore, John F.; Shapiro, Sondra S.

    1988-03-01

    The application of knowledge-based processing in image understanding systems has always occurred at a high level. These approaches have generated great claims, but limited results as they are basically simple forward chaining rule systems (e.g., if object on a road, then object is a vehicle). The application of heuristic reasoning to the low-level processing (e.g., image enhancement, segmentation, feature extraction, and classification) is a requirement to provide more accurate object and region information for high-level analysis, and truly integrate artificial intelligence throughout the entire system rather than as a post processing afterthought. This paper addresses the design and development of an integrated knowledge-based vision system in three phases. First, the application of knowledge base system techniques to image understanding is analyzed in light of deficiencies and limitations. This analysis is then exploited to produce a synergistically integrated system design. Second, the application of heuristics to low-level processing is discussed with specific application in the areas of image enhancement and segmentation. Finally, conclusions drawn to date on system performance will be presented in association with a mapping of how they are directing future work in this area.

  20. Near-infrared dyes for molecular probes and imaging

    NASA Astrophysics Data System (ADS)

    Patonay, Gabor; Beckford, Garfield; Strekowski, Lucjan; Henary, Maged; Kim, Jun Seok; Crow, Sidney

    2009-02-01

    Near-Infrared (NIR) fluorescence has been used both as an analytical tool as molecular probes and in in vitro or in vivo imaging of individual cells and organs. The NIR region (700-1100 nm) is ideal with regard to these applications due to the inherently lower background interference and the high molar absorptivities of NIR chromophores. NIR dyes are also useful in studying binding characteristics of large biomolecules, such as proteins. Throughout these studies, different NIR dyes have been evaluated to determine factors that control binding to biomolecules, including serum albumins. Hydrophobic character of NIR dyes were increased by introducing alkyl and aryl groups, and hydrophilic moieties e.g., polyethylene glycols (PEG) were used to increase aqueous solubility. Recently, our research group introduced bis-cyanines as innovative NIR probes. Depending on their microenvironment, bis-cyanines can exist as an intramolecular dimer with the two cyanines either in a stacked form, or in a linear conformation in which the two subunits do not interact with each other. In this intramolecular H-aggregate, the chromophore has a low extinction coefficient and low fluorescence quantum yield. Upon addition of biomolecules, the H-and D- bands are decreased and the monomeric band is increased, with concomitant increase in fluorescence intensity. Introduction of specific moieties into the NIR dye molecules allows for the development of physiological molecular probes to detect pH, metal ions and other parameters. Examples of these applications include imaging and biomolecule characterizations. Water soluble dyes are expected to be excellent candidates for both in vitro and in vivo imaging of cells and organs.

  1. Near Infrared Imaging of Molecular Beacons in Cancers

    NASA Astrophysics Data System (ADS)

    Chance, Britton

    2001-03-01

    The recent demonstrations of the efficacy of the tumor to background contrast in breast cancer using the tricarbo-cyanine near infrared (NIR) agent with time domain 2-D imaging presages the greater efficacy of site-directed optical contrast agents for early detection of cancers which show contrast (tissue to background) of over 20 fold. Further increases of contrast are obtained with structures that quench the fluorescence until the agent is delivered, recognized, and opened by specific enzymatic activity of the tumor. These are termed ``Molecular Beacons". In order to image the localization of the Beacons, we employ light pen (< 40μ) scanning of the freeze trapped tumor in order to immobilize the tissue, to increase the fluorescence quantum yield and to limit the penetration of the excitation to a thin superficial layer (< 20μ). Precision milling of layers (> 20μ) in LN2 gives the desired 3D high resolution image of the location of the Beacon within in the cancer cell. Since cancer prevention is linked to early detection, the high signal to background obtainable with Molecular Beacons enables the detection of very early subsurface cancers, especially breast and prostate (NIH, UIP). Thus the fluorescent Beacon excites and emits in the NIR window and signals from several cm deep in breast are detected by diffusive wave optical tomography (DWOT). Detection of objects (< 1 mm) is achieved by phased array optical system using 0^O, 180^O 50 MHz modulation of pairs of laser diodes (780 nm) and fluorescence detection (> 800 nm) affording 0.2 mm object detection of even low Beacon concentrations. One, two, and 3-D localization is made possible by one, two, and three orthogonal phase array null planes.

  2. Graphene-based nanomaterials as molecular imaging agents.

    PubMed

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

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed. PMID:25857851

  3. Molecular and Ionized Hydrogen in 30 Doradus. I. Imaging Observations

    NASA Astrophysics Data System (ADS)

    Yeh, Sherry C. C.; Seaquist, Ernest R.; Matzner, Christopher D.; Pellegrini, Eric W.

    2015-07-01

    We present the first fully calibrated H2 1-0 S(1) image of the entire 30 Doradus nebula. The observations were conducted using the NOAO Extremely Wide-field Infrared Imager (NEWFIRM) on the CTIO 4 m Blanco Telescope. Together with a NEWFIRM Brγ image of 30 Doradus, our data reveal the morphologies of the warm molecular gas and ionized gas in 30 Doradus. The brightest H2-emitting area, which extends from the northeast to the southwest of R136, is a photodissociation region (PDR) viewed face-on, while many clumps and pillar features located at the outer shells of 30 Doradus are PDRs viewed edge-on. Based on the morphologies of H2, Brγ, CO, and 8 μm emission, the H2 to Brγ line ratio, and Cloudy models, we find that the H2 emission is formed inside the PDRs of 30 Doradus, 2-3 pc to the ionization front of the H ii region, in a relatively low-density environment <104 cm-3. Comparisons with Brγ, 8 μm, and CO emission indicate that H2 emission is due to fluorescence, and provide no evidence for shock excited emission of this line.

  4. Molecular Imaging of Metabolic Reprograming in Mutant IDH Cells

    PubMed Central

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

    2016-01-01

    Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70–90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG). Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG). In turn, 2-HG, which has been termed an “oncometabolite,” inhibits key α-KG-dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprograming that extends beyond 2-HG production, and this reprograming often differs from what has been previously reported in other cancer types. In this review, we will discuss in detail what is known to date about the metabolic reprograming of mutant IDH cells, and how this reprograming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells, and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo. PMID:27014635

  5. Design and Fabrication of Vertically-Integrated CMOS Image Sensors

    PubMed Central

    Skorka, Orit; Joseph, Dileepan

    2011-01-01

    Technologies to fabricate integrated circuits (IC) with 3D structures are an emerging trend in IC design. They are based on vertical stacking of active components to form heterogeneous microsystems. Electronic image sensors will benefit from these technologies because they allow increased pixel-level data processing and device optimization. This paper covers general principles in the design of vertically-integrated (VI) CMOS image sensors that are fabricated by flip-chip bonding. These sensors are composed of a CMOS die and a photodetector die. As a specific example, the paper presents a VI-CMOS image sensor that was designed at the University of Alberta, and fabricated with the help of CMC Microsystems and Micralyne Inc. To realize prototypes, CMOS dies with logarithmic active pixels were prepared in a commercial process, and photodetector dies with metal-semiconductor-metal devices were prepared in a custom process using hydrogenated amorphous silicon. The paper also describes a digital camera that was developed to test the prototype. In this camera, scenes captured by the image sensor are read using an FPGA board, and sent in real time to a PC over USB for data processing and display. Experimental results show that the VI-CMOS prototype has a higher dynamic range and a lower dark limit than conventional electronic image sensors. PMID:22163860

  6. MICROBASE: An integrated paleontological database and image cataloging system

    SciTech Connect

    Becker, R.C. ); Goodman, D.K. ); Couvering, J.V. ); Ford, L.N. Jr. ); Albert, N.R. )

    1991-08-01

    MICROBASE (MICROpaleontology dataBASE) is an integrated database and image retrieval system designed to increase the efficiency with which paleontologists access paleontological and biostratigraphic data. The project is funded by a consortium of oil companies and coordinated by the American Association of Stratigraphic Palynologists. MICROBASE is a PC-based MS DOS-compatible system operating under Microsoft Windows 3.0 that takes advantage of the latest developments in both analog (video) and digital technology. Images are captured using a video camera mounted on a microscope, or with high-resolution scanner for photographic source material. The image is saved either as digital file or as an analog frame on a Panasonic optical disk recorded (OMDR). The OMDR can store 108,000 images on the 12-in. disk with a retrieval and display time of less than 0.7 s. Microfossil data (nomenclature, synonymy, descriptions, stratigraphic distribution etc.) are stored as relational tables in an ORACLE DBMS (PALeontological CATalog, or PALCAT). These textural data are linked to multiple images for each taxon. MICROBASE is the first integrated and widely-supported system to electronically archive paleontological data, regardless of fossil group. It provides rapid, easy to access to paleontological data, resulting in standardized taxonomy, more efficient identification procedures, substantially reduced learning curves for persons unfamiliar with particular groups, and more effective retention of the cumulative expertise of experienced paleontologists. The Ellis and Messina Catalog of Foraminifera is the first paleontological catalog available on the MICROBASE system.

  7. Providing integrity and authenticity in DICOM images: a novel approach.

    PubMed

    Kobayashi, Luiz Octavio Massato; Furuie, Sergio Shiguemi; Barreto, Paulo Sergio Licciardi Messeder

    2009-07-01

    The increasing adoption of information systems in healthcare has led to a scenario where patient information security is more and more being regarded as a critical issue. Allowing patient information to be in jeopardy may lead to irreparable damage, physically, morally, and socially to the patient, potentially shaking the credibility of the healthcare institution. Medical images play a crucial role in such context, given their importance in diagnosis, treatment, and research. Therefore, it is vital to take measures in order to prevent tampering and determine their provenance. This demands adoption of security mechanisms to assure information integrity and authenticity. There are a number of works done in this field, based on two major approaches: use of metadata and use of watermarking. However, there still are limitations for both approaches that must be properly addressed. This paper presents a new method using cryptographic means to improve trustworthiness of medical images, providing a stronger link between the image and the information on its integrity and authenticity, without compromising image quality to the end user. Use of Digital Imaging and Communications in Medicine structures is also an advantage for ease of development and deployment. PMID:19244022

  8. Final Report for Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Glotzer, Sharon C.

    2013-08-28

    In collaboration with researchers at Vanderbilt University, North Carolina State University, Princeton and Oakridge National Laboratory we developed multiscale modeling and simulation methods capable of modeling the synthesis, assembly, and operation of molecular electronics devices. Our role in this project included the development of coarse-grained molecular and mesoscale models and simulation methods capable of simulating the assembly of millions of organic conducting molecules and other molecular components into nanowires, crossbars, and other organized patterns.

  9. Integrated transrectal probe for translational ultrasound-photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Bell, Kevan L.; Harrison, Tyler; Usmani, Nawaid; Zemp, Roger J.

    2016-03-01

    A compact photoacoustic transrectal probe is constructed for improved imaging in brachytherapy treatment. A 192 element 5 MHz linear transducer array is mounted inside a small 3D printed casing along with an array of optical fibers. The device is fed by a pump laser and tunable NIR-optical parametric oscillator with data collected by a Verasonics ultrasound platform. This assembly demonstrates improved imaging of brachytherapy seeds in phantoms with depths up to 5 cm. The tuneable excitation in combination with standard US integration provides adjustable contrast between the brachytherapy seeds, blood filled tubes and background tissue.

  10. Integrated filter and detector array for spectral imaging

    NASA Technical Reports Server (NTRS)

    Labaw, Clayton C. (Inventor)

    1992-01-01

    A spectral imaging system having an integrated filter and photodetector array is disclosed. The filter has narrow transmission bands which vary in frequency along the photodetector array. The frequency variation of the transmission bands is matched to, and aligned with, the frequency variation of a received spectral image. The filter is deposited directly on the photodetector array by a low temperature deposition process. By depositing the filter directly on the photodetector array, permanent alignment is achieved for all temperatures, spectral crosstalk is substantially eliminated, and a high signal to noise ratio is achieved.

  11. MO-C-BRE-01: The WMIS-AAPM Joint Symposium: Advances in Molecular Imaging

    SciTech Connect

    Contag, C; Pogue, B; Lewis, J

    2014-06-15

    This joint symposium of the World Molecular Imaging Society (WMIS) and the AAPM includes three luminary speakers discussing work in new paradigms of molecular imaging in cancer (Contag), applications of optical imaging technologies to radiation therapy (Pogue) and an update on PET imaging as a surrogate biomarker for cancer progression and response to therapy. Learning Objectives: Appreciate the current trends in molecular and systems imaging. Understand how optical imaging technologies, and particularly Cerenkov detectors, can be used in advancing radiation oncology. Stay current on new PET tracers - and targets - of interest in cancer treatment.

  12. MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

    PubMed Central

    Rauser, Sandra; Deininger, Sören-Oliver; Höfler, Heinz

    2008-01-01

    Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings. PMID:18618129

  13. High-speed laser Doppler perfusion imaging using an integrating CMOS image sensor.

    PubMed

    Serov, Alexandre; Lasser, Theo

    2005-08-22

    This paper describes the design and the performance of a new high-speed laser Doppler imaging system for monitoring blood flow over an area of tissue. The new imager delivers high-resolution flow images (256x256 pixels) every 2 to 10 seconds, depending on the number of points in the acquired time-domain signal (32-512 points). This new imaging modality utilizes a digital integrating CMOS image sensor to detect Doppler signals in a plurality of points over the area illuminated by a divergent laser beam of a uniform intensity profile. The integrating property of the detector improves the signal-to-noise ratio of the measurements, which results in high-quality flow images. We made a series of measurements in vitro to test the performance of the system in terms of bandwidth, SNR, etc. Subsequently we give some examples of flow-related images measured on human skin, thus demonstrating the performance of the imager in vivo. The perspectives for future implementations of the imager for clinical and physiological applications are discussed. PMID:19498655

  14. Accuracy assessment of topographic mapping using UAV image integrated with satellite images

    NASA Astrophysics Data System (ADS)

    Azmi, S. M.; Ahmad, Baharin; Ahmad, Anuar

    2014-02-01

    Unmanned Aerial Vehicle or UAV is extensively applied in various fields such as military applications, archaeology, agriculture and scientific research. This study focuses on topographic mapping and map updating. UAV is one of the alternative ways to ease the process of acquiring data with lower operating costs, low manufacturing and operational costs, plus it is easy to operate. Furthermore, UAV images will be integrated with QuickBird images that are used as base maps. The objective of this study is to make accuracy assessment and comparison between topographic mapping using UAV images integrated with aerial photograph and satellite image. The main purpose of using UAV image is as a replacement for cloud covered area which normally exists in aerial photograph and satellite image, and for updating topographic map. Meanwhile, spatial resolution, pixel size, scale, geometric accuracy and correction, image quality and information contents are important requirements needed for the generation of topographic map using these kinds of data. In this study, ground control points (GCPs) and check points (CPs) were established using real time kinematic Global Positioning System (RTK-GPS) technique. There are two types of analysis that are carried out in this study which are quantitative and qualitative assessments. Quantitative assessment is carried out by calculating root mean square error (RMSE). The outputs of this study include topographic map and orthophoto. From this study, the accuracy of UAV image is ± 0.460 m. As conclusion, UAV image has the potential to be used for updating of topographic maps.

  15. A web service for enabling medical image retrieval integrated into a social medical image sharing platform.

    PubMed

    Niinimäki, Marko; Zhou, Xin; de la Vega, Enrique; Cabrer, Miguel; Müller, Henning

    2010-01-01

    Content-based visual image access is in the process from a research domain towards real applications. So far, most image retrieval applications have been in one specialized domain such as lung CTs as diagnosis aid or for classification of general images based on anatomic region, modality, and view. This article describes the use of a content-based image retrieval system in connection with the medical image sharing platform MEDTING, so a data set with a very large variety. Similarity retrieval is possible for all cases of the social image sharing platform, so cases can be linked by either visual similarity or similarity in keywords. The visual retrieval search is based on the GIFT (GNU Image Finding Tool). The technology for updating the index with new images added by users employs RSS (Really Simple Syndication) feeds. The ARC (Advanced Resource Connector) middleware is used for the implementation of a web service for similarity retrieval, simplifying the integration of this service. Novelty of this article is the application/integration and image updating strategy. Retrieval methods themselves employ existing techniques that are all open source and can easily be reproduced. PMID:20841889

  16. Integrating Medical Imaging Analyses through a High-throughput Bundled Resource Imaging System

    PubMed Central

    Covington, Kelsie; Welch, E. Brian; Jeong, Ha-Kyu; Landman, Bennett A.

    2011-01-01

    Exploitation of advanced, PACS-centric image analysis and interpretation pipelines provides well-developed storage, retrieval, and archival capabilities along with state-of-the-art data providence, visualization, and clinical collaboration technologies. However, pursuit of integrated medical imaging analysis through a PACS environment can be limiting in terms of the overhead required to validate, evaluate and integrate emerging research technologies. Herein, we address this challenge through presentation of a high-throughput bundled resource imaging system (HUBRIS) as an extension to the Philips Research Imaging Development Environment (PRIDE). HUBRIS enables PACS-connected medical imaging equipment to invoke tools provided by the Java Imaging Science Toolkit (JIST) so that a medical imaging platform (e.g., a magnetic resonance imaging scanner) can pass images and parameters to a server, which communicates with a grid computing facility to invoke the selected algorithms. Generated images are passed back to the server and subsequently to the imaging platform from which the images can be sent to a PACS. JIST makes use of an open application program interface layer so that research technologies can be implemented in any language capable of communicating through a system shell environment (e.g., Matlab, Java, C/C++, Perl, LISP, etc.). As demonstrated in this proof-of-concept approach, HUBRIS enables evaluation and analysis of emerging technologies within well-developed PACS systems with minimal adaptation of research software, which simplifies evaluation of new technologies in clinical research and provides a more convenient use of PACS technology by imaging scientists. PMID:21841899

  17. Integrating Medical Imaging Analyses through a High-throughput Bundled Resource Imaging System.

    PubMed

    Covington, Kelsie; Welch, E Brian; Jeong, Ha-Kyu; Landman, Bennett A

    2011-01-01

    Exploitation of advanced, PACS-centric image analysis and interpretation pipelines provides well-developed storage, retrieval, and archival capabilities along with state-of-the-art data providence, visualization, and clinical collaboration technologies. However, pursuit of integrated medical imaging analysis through a PACS environment can be limiting in terms of the overhead required to validate, evaluate and integrate emerging research technologies. Herein, we address this challenge through presentation of a high-throughput bundled resource imaging system (HUBRIS) as an extension to the Philips Research Imaging Development Environment (PRIDE). HUBRIS enables PACS-connected medical imaging equipment to invoke tools provided by the Java Imaging Science Toolkit (JIST) so that a medical imaging platform (e.g., a magnetic resonance imaging scanner) can pass images and parameters to a server, which communicates with a grid computing facility to invoke the selected algorithms. Generated images are passed back to the server and subsequently to the imaging platform from which the images can be sent to a PACS. JIST makes use of an open application program interface layer so that research technologies can be implemented in any language capable of communicating through a system shell environment (e.g., Matlab, Java, C/C++, Perl, LISP, etc.). As demonstrated in this proof-of-concept approach, HUBRIS enables evaluation and analysis of emerging technologies within well-developed PACS systems with minimal adaptation of research software, which simplifies evaluation of new technologies in clinical research and provides a more convenient use of PACS technology by imaging scientists. PMID:21841899

  18. Integration of Image-Derived and Pos-Derived Features for Image Blur Detection

    NASA Astrophysics Data System (ADS)

    Teo, Tee-Ann; Zhan, Kai-Zhi

    2016-06-01

    The image quality plays an important role for Unmanned Aerial Vehicle (UAV)'s applications. The small fixed wings UAV is suffering from the image blur due to the crosswind and the turbulence. Position and Orientation System (POS), which provides the position and orientation information, is installed onto an UAV to enable acquisition of UAV trajectory. It can be used to calculate the positional and angular velocities when the camera shutter is open. This study proposes a POS-assisted method to detect the blur image. The major steps include feature extraction, blur image detection and verification. In feature extraction, this study extracts different features from images and POS. The image-derived features include mean and standard deviation of image gradient. For POS-derived features, we modify the traditional degree-of-linear-blur (blinear) method to degree-of-motion-blur (bmotion) based on the collinear condition equations and POS parameters. Besides, POS parameters such as positional and angular velocities are also adopted as POS-derived features. In blur detection, this study uses Support Vector Machines (SVM) classifier and extracted features (i.e. image information, POS data, blinear and bmotion) to separate blur and sharp UAV images. The experiment utilizes SenseFly eBee UAV system. The number of image is 129. In blur image detection, we use the proposed degree-of-motion-blur and other image features to classify the blur image and sharp images. The classification result shows that the overall accuracy using image features is only 56%. The integration of image-derived and POS-derived features have improved the overall accuracy from 56% to 76% in blur detection. Besides, this study indicates that the performance of the proposed degree-of-motion-blur is better than the traditional degree-of-linear-blur.

  19. Molecular Assemblies, Genes and Genomics Integrated Efficiently (MAGGIE)

    SciTech Connect

    Baliga, Nitin S

    2011-05-26

    Final report on MAGGIE. We set ambitious goals to model the functions of individual organisms and their community from molecular to systems scale. These scientific goals are driving the development of sophisticated algorithms to analyze large amounts of experimental measurements made using high throughput technologies to explain and predict how the environment influences biological function at multiple scales and how the microbial systems in turn modify the environment. By experimentally evaluating predictions made using these models we will test the degree to which our quantitative multiscale understanding wilt help to rationally steer individual microbes and their communities towards specific tasks. Towards this end we have made substantial progress towards understanding evolution of gene families, transcriptional structures, detailed structures of keystone molecular assemblies (proteins and complexes), protein interactions, biological networks, microbial interactions, and community structure. Using comparative analysis we have tracked the evolutionary history of gene functions to understand how novel functions evolve. One level up, we have used proteomics data, high-resolution genome tiling microarrays, and 5' RNA sequencing to revise genome annotations, discover new genes including ncRNAs, and map dynamically changing operon structures of five model organisms: For Desulfovibrio vulgaris Hildenborough, Pyrococcus furiosis, Sulfolobus solfataricus, Methanococcus maripaludis and Haiobacterium salinarum NROL We have developed machine learning algorithms to accurately identify protein interactions at a near-zero false positive rate from noisy data generated using tagfess complex purification, TAP purification, and analysis of membrane complexes. Combining other genome-scale datasets produced by ENIGMA (in particular, microarray data) and available from literature we have been able to achieve a true positive rate as high as 65% at almost zero false positives when

  20. Molecular imaging of apoptosis for early prediction of therapy efficiency.

    PubMed

    De Saint-Hubert, Marijke; Bauwens, Matthias; Mottaghy, Felix M

    2014-01-01

    Evasion of apoptosis is one of the hallmarks of cancer and any effective therapy primarily attempts to induce apoptosis. The evaluation of the degree of success of cancer therapy is currently mainly based on clinical and laboratory parameters and in a later stage on tumor shrinkage. However, none of these parameters provide an objective and early analysis of a therapeutic effect. Molecular imaging may provide a tool for this purpose by using not only pathophysiological but also biochemical effects of the therapy. First in the field, FDG-PET has been explored and demonstrated to offer insight in the amount of viable cells, even though false positives are commonly due to the lack of specificity of this particular radiopharmaceutical. More specific markers target the dying cells instead of those remaining alive. Specific apoptosis markers have been developed of which the radiolabeled Annexin A5 is the most intensely studied probe. Site-specific labeling strategies have improved this imaging probe with good results both in pre-clinical studies and in clinical trials, with promises for clinical applications. Caspase sensitive probes, such as the isatines, can also effectively image apoptosis but are limited due to the high background activities. More recent discoveries of small apoptosis sensitive probes, such as (18)F-ML10, are currently being explored. In this review, the most important apoptosis sensitive probes are described from both a pre-clinical and a clinical perspective, highlighting their potential but also their limitations as an early marker for therapeutic success. It seems that apoptosis imaging can help to guide therapy, not by replacing the current methodology but by providing additional and useful information. PMID:24025102

  1. On noise in time-delay integration CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Levski, Deyan; Choubey, Bhaskar

    2016-05-01

    Time delay integration sensors are of increasing interest in CMOS processes owing to their low cost, power and ability to integrate with other circuit readout blocks. This paper presents an analysis of the noise contributors in current day CMOS Time-Delay-Integration image sensors with various readout architectures. An analysis of charge versus voltage domain readout modes is presented, followed by a noise classification of the existing Analog Accumulator Readout (AAR) and Digital Accumulator Readout (DAR) schemes for TDI imaging. The analysis and classification of existing readout schemes include, pipelined charge transfer, buffered direct injection, voltage as well as current-mode analog accumulators and all-digital accumulator techniques. Time-Delay-Integration imaging modes in CMOS processes typically use an N-number of readout steps, equivalent to the number of TDI pixel stages. In CMOS TDI sensors, where voltage domain readout is used, the requirements over speed and noise of the ADC readout chain are increased due to accumulation of the dominant voltage readout and ADC noise with every stage N. Until this day, the latter is the primary reason for a leap-back of CMOS TDI sensors as compared to their CCD counterparts. Moreover, most commercial CMOS TDI implementations are still based on a charge-domain readout, mimicking a CCD-like operation mode. Thus, having a good understanding of each noise contributor in the signal chain, as well as its magnitude in different readout architectures, is vital for the design of future generation low-noise CMOS TDI image sensors based on a voltage domain readout. This paper gives a quantitative classification of all major noise sources for all popular implementations in the literature.

  2. Ge/Si Integrated Circuit For Infrared Imaging

    NASA Technical Reports Server (NTRS)

    Fathauer, Robert W.

    1990-01-01

    Proposed integrated circuit consists of focal-plane array of metal/germanium Schottky-barrier photodetectors on same chip with silicon-based circuits that processes signals from photodetectors. Made compatible with underlying silicon-based circuitry by growing germanium epitaxially on silicon circuit wafers. Metal deposited in ultrahigh vacuum immediately after growth of germanium. Combination of described techniques results in high-resolution infrared-imaging circuits of superior performance.

  3. Emerging clinical applications of PET based molecular imaging in oncology: the promising future potential for evolving personalized cancer care

    PubMed Central

    Dhingra, Vandana K; Mahajan, Abhishek; Basu, Sandip

    2015-01-01

    This review focuses on the potential of advanced applications of functional molecular imaging in assessing tumor biology and cellular characteristics with emphasis on positron emission tomography (PET) applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers. The inherent heterogeneity of cancer cells with their varied cellular biology and metabolic and receptor phenotypic expression in each individual patient and also intra-and inter-lesionally in the same individual mandates for transitioning from a generalized “same-size-fits-all” approach to personalized medicine in oncology. The past two decades have witnessed improvement of oncological imaging through CT, MR imaging, PET, subsequent movement through hybrid or fusion imaging with PET/CT and single-photon emission computerized tomography (SPECT-CT), and now toward the evolving PET/MR imaging. These recent developments have proven invaluable in enhancing oncology care and have the potential to help image the tumor biology at the cellular level, followed by providing a tailored treatment. Molecular imaging, integrated diagnostics or Radiomics, biology-driven interventional radiology and theranostics, all hold immense potential to serve as a guide to give “start and stop” treatment for a patient on an individual basis. This will likely have substantial impact on both treatment costs and outcomes. In this review, we bring forth the current trends in molecular imaging with established techniques (PET/CT), with particular emphasis on newer molecules (such as amino acid metabolism and hypoxia imaging, somatostatin receptor based imaging, and hormone receptor imaging) and further potential for FDG. An introductory discussion on the novel hybrid imaging techniques such as PET/MR is also made to understand the futuristic trends. PMID:26752813

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

  6. A Raman-based endoscopic strategy for multiplexed molecular imaging.

    PubMed

    Zavaleta, Cristina L; Garai, Ellis; Liu, Jonathan T C; Sensarn, Steven; Mandella, Michael J; Van de Sompel, Dominique; Friedland, Shai; Van Dam, Jacques; Contag, Christopher H; Gambhir, Sanjiv S

    2013-06-18

    Endoscopic imaging is an invaluable diagnostic tool allowing minimally invasive access to tissues deep within the body. It has played a key role in screening colon cancer and is credited with preventing deaths through the detection and removal of precancerous polyps. However, conventional white-light endoscopy offers physicians structural information without the biochemical information that would be advantageous for early detection and is essential for molecular typing. To address this unmet need, we have developed a unique accessory, noncontact, fiber optic-based Raman spectroscopy device that has the potential to provide real-time, multiplexed functional information during routine endoscopy. This device is ideally suited for detection of functionalized surface-enhanced Raman scattering (SERS) nanoparticles as molecular imaging contrast agents. This device was designed for insertion through a clinical endoscope and has the potential to detect and quantify the presence of a multiplexed panel of tumor-targeting SERS nanoparticles. Characterization of the Raman instrument was performed with SERS particles on excised human tissue samples, and it has shown unsurpassed sensitivity and multiplexing capabilities, detecting 326-fM concentrations of SERS nanoparticles and unmixing 10 variations of colocalized SERS nanoparticles. Another unique feature of our noncontact Raman endoscope is that it has been designed for efficient use over a wide range of working distances from 1 to 10 mm. This is necessary to accommodate for imperfect centering during endoscopy and the nonuniform surface topology of human tissue. Using this endoscope as a key part of a multiplexed detection approach could allow endoscopists to distinguish between normal and precancerous tissues rapidly and to identify flat lesions that are otherwise missed. PMID:23703909

  7. Structure and discrimination in chiral fluids: A molecular dynamics and integral equation study

    NASA Astrophysics Data System (ADS)

    Cann, N. M.; Das, B.

    2000-08-01

    An analysis of structure and discrimination in simple chiral fluids is presented. The chiral molecules consist of a central carbon bonded to four distinct groups. Molecular-dynamics simulations have been performed on a one-component chiral fluid and on two racemic mixtures. For the racemates, discrimination, as measured by differences in pair distribution functions, is present but found to be small. Intermolecular pair interaction energies are found to be good predictors of the magnitude and the sign (mirror-image pairs favored) of the differences observed in site-site distribution functions. For the one-component fluid, the quality of structural predictions from the reference-interaction-site method and Chandler-Silbey-Ladanyi (CSL) integral equation theories, with the hypernetted chain (HNC) and Percus-Yevick closures, has been examined. These theories generally provide a qualitatively correct description of the site-site distributions. Extensions beyond the HNC level have been explored: Two-field-point bridge diagrams have been explicitly evaluated and included in the CSL theory. The inclusion of these diagrams significantly improves the quality of the integral equation theories. Since the CSL theory has not been used extensively, and bridge diagrams have been evaluated in only a few instances, a detailed analysis of their impact is presented. For racemic mixtures, diagram evaluation is shown to be crucial. Specifically, the differences in site-site distributions for sites on identical and mirror-image molecules are found to originate from bridge diagrams which involve interactions between four-site, or larger, clusters. Discrimination cannot be predicted from an integral equation theory which neglects these diagrams.

  8. Integration of optical imaging with a small animal irradiator

    SciTech Connect

    Weersink, Robert A.; Ansell, Steve; Wang, An; Wilson, Graham; Shah, Duoaud; Lindsay, Patricia E.; Jaffray, David A.

    2014-10-15

    Purpose: The authors describe the integration of optical imaging with a targeted small animal irradiator device, focusing on design, instrumentation, 2D to 3D image registration, 2D targeting, and the accuracy of recovering and mapping the optical signal to a 3D surface generated from the cone-beam computed tomography (CBCT) imaging. The integration of optical imaging will improve targeting of the radiation treatment and offer longitudinal tracking of tumor response of small animal models treated using the system. Methods: The existing image-guided small animal irradiator consists of a variable kilovolt (peak) x-ray tube mounted opposite an aSi flat panel detector, both mounted on a c-arm gantry. The tube is used for both CBCT imaging and targeted irradiation. The optical component employs a CCD camera perpendicular to the x-ray treatment/imaging axis with a computer controlled filter for spectral decomposition. Multiple optical images can be acquired at any angle as the gantry rotates. The optical to CBCT registration, which uses a standard pinhole camera model, was modeled and tested using phantoms with markers visible in both optical and CBCT images. Optically guided 2D targeting in the anterior/posterior direction was tested on an anthropomorphic mouse phantom with embedded light sources. The accuracy of the mapping of optical signal to the CBCT surface was tested using the same mouse phantom. A surface mesh of the phantom was generated based on the CBCT image and optical intensities projected onto the surface. The measured surface intensity was compared to calculated surface for a point source at the actual source position. The point-source position was also optimized to provide the closest match between measured and calculated intensities, and the distance between the optimized and actual source positions was then calculated. This process was repeated for multiple wavelengths and sources. Results: The optical to CBCT registration error was 0.8 mm. Two

  9. Development of Integration and Adjustment Method for Sequential Range Images

    NASA Astrophysics Data System (ADS)

    Nagara, K.; Fuse, T.

    2015-05-01

    With increasing widespread use of three-dimensional data, the demand for simplified data acquisition is also increasing. The range camera, which is a simplified sensor, can acquire a dense-range image in a single shot; however, its measuring coverage is narrow and its measuring accuracy is limited. The former drawback had be overcome by registering sequential range images. This method, however, assumes that the point cloud is error-free. In this paper, we develop an integration method for sequential range images with error adjustment of the point cloud. The proposed method consists of ICP (Iterative Closest Point) algorithm and self-calibration bundle adjustment. The ICP algorithm is considered an initial specification for the bundle adjustment. By applying the bundle adjustment, coordinates of the point cloud are modified and the camera poses are updated. Through experimentation on real data, the efficiency of the proposed method has been confirmed.

  10. Molecular imaging of biological tissue using gas cluster ions

    PubMed Central

    Tian, Hua; Wucher, Andreas; Winograd, Nicholas

    2015-01-01

    An Arn+ (n = 1–6000) gas cluster ion source has been utilized to map the chemical distribution of lipids in a mouse brain tissue section. We also show that the signal from high mass species can be further enhanced by doping a small amount of CH4 into the Ar cluster to enhance the ionization of several biologically important molecules. Coupled with secondary ion mass spectrometry instrumentation which utilizes a continuous Ar cluster ion projectile, maximum spatial resolution and maximum mass resolution can be achieved at the same time. With this arrangement, it is possible to achieve chemically resolved molecular ion images at the 4-µm resolution level. The focused Arn+/[Arx(CH4)y]+ beams (4–10 µm) have been applied to the study of untreated mouse brain tissue. A high signal level of molecular ions and salt adducts, mainly from various phosphocholine lipids, has been seen and directly used to map the chemical distribution. The signal intensity obtained using the pure Ar cluster source, the CH4-doped cluster source and C60 is also presented. PMID:26207076

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

    PubMed Central

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

    2011-01-01

    This work presents simultaneous imaging and detection of three different cell receptors using three types of plasmonic nanoparticles (NPs). The size, shape, and composition-dependent scattering profiles of these NPs allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, tags consisting of anti-epidermal growth factor receptor gold nanorods, anti-insulin-like growth factor 1-R silver nanospheres, and human epidermal growth factor receptor 2Ab gold nanospheres were developed to monitor the expression of receptors commonly overexpressed by cancer cells. These labels were chosen because they scatter strongly in distinct spectral windows. A hyperspectral darkfield microspectroscopy system was developed to record the scattering spectra of cells labeled with these molecular tags. Simultaneous monitoring of multiple tags may lead to applications such as profiling of cell line immunophenotype and investigation of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze NP tag specificity as well as their interactions. Distinct resonance peaks were observed in these studies, showing the ability to characterize cell lines using conjugated NPs. However, interpreting shifts in these peaks due to changes in a cellular dielectric environment may be complicated by plasmon coupling between NPs bound to proximal receptors and other coupling mechanisms due to the receptors themselves. PMID:22112108

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    This work presents simultaneous imaging and detection of three types of cell receptors using three types of plasmonic nanoparticles. The size, shape, and composition-dependent scattering profiles of these particles allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, a system of tags consisting of anti-EGFR gold nanorods, anti-IGF1R silver nanospheres, and anti-HER-2 gold nanospheres was developed for monitoring the expression of three commonly overexpressed receptors in cancer cells. These labels were chosen because they each scatter strongly in a distinct spectral window. A hyperspectral dark-field microscope was developed to record the scattering spectra of cells labeled with these molecular tags. The ability to monitor multiple tags simultaneously may lead to applications such as profiling the immunophenotype of cell lines and gaining better knowledge of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze the specificity of the nanoparticle tags as well as their effect on one another. While distinct resonance peaks in these studies show the ability to characterize cell lines using conjugated nanoparticles, shifts in these peaks also indicate changes in the cellular dielectric environment which may not be distinct from plasmon coupling between nanoparticles bound to proximal receptors.

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  14. Design of the CHARIS integral field spectrograph for exoplanet imaging

    NASA Astrophysics Data System (ADS)

    Groff, Tyler D.; Peters, Mary Anne; Kasdin, N. Jeremy; Knapp, Gillian; Galvin, Michael; Carr, Michael; McElwain, Michael W.; Brandt, Timothy; Janson, Markus; Gunn, James E.; Lupton, Robert; Guyon, Olivier; Martinache, Frantz; Jovanovic, Nemanja; Hayashi, Masahiko; Takato, Naruhisa

    2013-09-01

    Princeton University is building an integral field spectrograph (IFS), the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS), for integration with the Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system and the AO188 adaptive optics system on the Subaru telescope. CHARIS and SCExAO will measure spectra of hot, young Jovian planets in a coronagraphic image across J, H, and K bands down to an 80 milliarcsecond inner working angle. SCExAO's coronagraphs and wavefront control system will make it possible to detect companions five orders of magnitude dimmer than their parent star. However, quasi-static speckles in the image contaminate the signal from the planet. In an IFS this also causes uncertainty in the spectra due to diffractive cross-contamination, commonly referred to as crosstalk. Post-processing techniques can subtract these speckles, but they can potentially skew spectral measurements, become less effective at small angular separation, and at best can only reduce the crosstalk down to the photon noise limit of the contaminating signal. CHARIS will address crosstalk effects of a high contrast image through hardware design, which drives the optical and mechanical design of the assembly. The work presented here sheds light on the optical and mechanical considerations taken in designing the IFS to provide high signal-to-noise spectra in a coronagraphic image from and extreme adaptive optics image. The design considerations and lessons learned are directly applicable to future exoplanet instrumentation for extremely large telescopes and space observatories capable of detecting rocky planets in the habitable zone.

  15. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  16. RAMP: a bioinformatics framework for researching imaging agents through molecular pathways.

    PubMed

    Khokhlovich, Edward; Wahl, Daniel; Masiello, Anthony; Parisot, Pierre; El-Ghatta, Stefan; Szustakowski, Joseph D; Nirmala, Nanguneri; Tuch, David S

    2013-01-01

    Signaling pathways are the fundamental grammar of cellular communication, yet few frameworks are available to analyze molecular imaging probes in the context of signaling pathways. Such a framework would aid in the design and selection of imaging probes for measuring specific signaling pathways and, vice versa, help illuminate which pathways are being assayed by a given probe. RAMP (Researching imaging Agents through Molecular Pathways) is a bioinformatics framework for connecting signaling pathways and imaging probes using a controlled vocabulary of the imaging targets. RAMP contains signaling pathway data from MetaCore, the Kyoto Encyclopedia of Genes and Genomes, and the Gene Ontology project; imaging probe data from the Molecular Imaging and Contrast Agent Database (MICAD); and tissue protein expression data from The Human Protein Atlas. The RAMP search tool is available at . Examples are presented to demonstrate the utility of RAMP for pathway-based searches of molecular imaging probes. PMID:23348786

  17. A solution for archiving and retrieving preclinical molecular imaging data in PACS using a DICOM gateway

    NASA Astrophysics Data System (ADS)

    Lee, Jasper; Liu, Bihui; Liu, Brent

    2011-03-01

    Advances in biology, computer technology and imaging technology have given rise to a scientific specialty referred to as molecular imaging, which is the in vivo imaging of cellular and molecular pathways using contrast-enhancing targeting agents. Increasing amounts of molecular imaging research are being performed at pre-clinical stages, generating diverse datasets that are unstructured and thereby lacking in archiving and distribution solutions. Since PACS in radiology is a mature clinical archiving solution, a method is proposed to convert current imaging files from preclinical molecular imaging studies into DICOM formats for archival and retrieval from PACS systems. A web-based DICOM gateway is presented with an emphasis on metadata mapping in the DICOM header, system connectivity, and overall user workflow. This effort to conform preclinical imaging data to the DICOM standard is necessary to utilize current PACS solutions for preclinical imaging data content archiving and distribution.

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

    PubMed Central

    Chen, Zhi-Yi; Yang, Feng; Lin, Yan; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    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. PMID:24696850

  19. Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

    2003-03-01

    Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

  20. Design of optimal collimation for dedicated molecular breast imaging systems

    PubMed Central

    Weinmann, Amanda L.; Hruska, Carrie B.; O’Connor, Michael K.

    2009-01-01

    Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7–10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5–3.2, while maintaining a collimator resolution of either ≤5 or ≤7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform MBI. PMID:19378745

  1. Design of optimal collimation for dedicated molecular breast imaging systems

    SciTech Connect

    Weinmann, Amanda L.; Hruska, Carrie B.; O'Connor, Michael K.

    2009-03-15

    Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7-10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5-3.2, while maintaining a collimator resolution of either {<=}5 or {<=}7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform MBI.

  2. Novel genotype-phenotype associations in human cancers enabled by advanced molecular platforms and computational analysis of whole slide images

    PubMed Central

    Cooper, Lee A.D.; Kong, Jun; Gutman, David A.; Dunn, William D.; Nalisnik, Michael; Brat, Daniel J.

    2014-01-01

    Technological advances in computing, imaging and genomics have created new opportunities for exploring relationships between histology, molecular events and clinical outcomes using quantitative methods. Slide scanning devices are now capable of rapidly producing massive digital image archives that capture histological details in high-resolution. Commensurate advances in computing and image analysis algorithms enable mining of archives to extract descriptions of histology, ranging from basic human annotations to automatic and precisely quantitative morphometric characterization of hundreds of millions of cells. These imaging capabilities represent a new dimension in tissue-based studies, and when combined with genomic and clinical endpoints, can be used to explore biologic characteristics of the tumor microenvironment and to discover new morphologic biomarkers of genetic alterations and patient outcomes. In this paper we review developments in quantitative imaging technology and illustrate how image features can be integrated with clinical and genomic data to investigate fundamental problems in cancer. Using motivating examples from the study of glioblastomas (GBMs), we demonstrate how public data from The Cancer Genome Atlas (TCGA) can serve as an open platform to conduct in silico tissue based studies that integrate existing data resources. We show how these approaches can be used to explore the relation of the tumor microenvironment to genomic alterations and gene expression patterns and to define nuclear morphometric features that are predictive of genetic alterations and clinical outcomes. Challenges, limitations and emerging opportunities in the area of quantitative imaging and integrative analyses are also discussed. PMID:25599536

  3. Signal-to-noise ratio for temporal integrated drifting images: a model for perceived image sharpening.

    PubMed

    Power, G J; Sturtz, K E

    2000-12-10

    A formulation of signal-to-noise ratio is constructed that uses temporal integrated images from image sequences. Given a blurred image that drifts horizontally at various speeds and at various linear blurs, we prove that this formulation of the signal-to-noise ratio consistently increases with an increase in speed. This increase is shown to model the trends in the human vision system by which drifting blurred images are perceived with increased sharpness. The existing widely used objective quality techniques fail to model the perceptual increase in sharpness. This new formulation, along with other objective quality measures, is tested on several blurred drifting image sequences. The new formulation reflects the theoretically predicted increase in perceived sharpness. PMID:18354675

  4. Final technical report for DOE Computational Nanoscience Project: Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Cummings, P. T.

    2010-02-08

    This document reports the outcomes of the Computational Nanoscience Project, "Integrated Multiscale Modeling of Molecular Computing Devices". It includes a list of participants and publications arising from the research supported.

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

    PubMed

    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

  6. Adaptive HIFU noise cancellation for simultaneous therapy and imaging using an integrated HIFU/imaging transducer

    PubMed Central

    Jeong, Jong Seob; Cannata, Jonathan Matthew; Shung, K Kirk

    2010-01-01

    It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than −40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of −20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe ‘ripples’ when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm × 20.0 mm dimensions

  7. Adaptive HIFU noise cancellation for simultaneous therapy and imaging using an integrated HIFU/imaging transducer.

    PubMed

    Jeong, Jong Seob; Cannata, Jonathan Matthew; Shung, K Kirk

    2010-04-01

    It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than -40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of -20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe 'ripples' when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm x 20.0 mm dimensions could

  8. Integrated terrain mapping with digital Landsat images in Queensland, Australia

    USGS Publications Warehouse

    Robinove, Charles Joseph

    1979-01-01

    Mapping with Landsat images usually is done by selecting single types of features, such as soils, vegetation, or rocks, and creating visually interpreted or digitally classified maps of each feature. Individual maps can then be overlaid on or combined with other maps to characterize the terrain. Integrated terrain mapping combines several terrain features into each map unit which, in many cases, is more directly related to uses of the land and to methods of land management than the single features alone. Terrain brightness, as measured by the multispectral scanners in Landsat 1 and 2, represents an integration of reflectance from the terrain features within the scanner's instantaneous field of view and is therefore more correlatable with integrated terrain units than with differentiated ones, such as rocks, soils, and vegetation. A test of the feasibilty of the technique of mapping integrated terrain units was conducted in a part of southwestern Queensland, Australia, in cooperation with scientists of the Queensland Department of Primary Industries. The primary purpose was to test the use of digital classification techniques to create a 'land systems map' usable for grazing land management. A recently published map of 'land systems' in the area (made by aerial photograph interpretation and ground surveys), which are integrated terrain units composed of vegetation, soil, topography, and geomorphic features, was used as a basis for comparison with digitally classified Landsat multispectral images. The land systems, in turn, each have a specific grazing capacity for cattle (expressed in beasts per km 2 ) which is estimated following analysis of both research results and property carrying capacities. Landsat images, in computer-compatible tape form, were first contrast-stretched to increase their visual interpretability, and digitally classified by the parallelepiped method into distinct spectral classes to determine their correspondence to the land systems classes and

  9. Diversification of Neoaves: integration of molecular sequence data and fossils

    PubMed Central

    Ericson, Per G.P; Anderson, Cajsa L; Britton, Tom; Elzanowski, Andrzej; Johansson, Ulf S; Källersjö, Mari; Ohlson, Jan I; Parsons, Thomas J; Zuccon, Dario; Mayr, Gerald

    2006-01-01

    Patterns of diversification and timing of evolution within Neoaves, which includes almost 95% of all bird species, are virtually unknown. On the other hand, molecular data consistently indicate a Cretaceous origin of many neoavian lineages and the fossil record seems to support an Early Tertiary diversification. Here, we present the first well-resolved molecular phylogeny for Neoaves, together with divergence time estimates calibrated with a large number of stratigraphically and phylogenetically well-documented fossils. Our study defines several well-supported clades within Neoaves. The calibration results suggest that Neoaves, after an initial split from Galloanseres in Mid-Cretaceous, diversified around or soon after the K/T boundary. Our results thus do not contradict palaeontological data and show that there is no solid molecular evidence for an extensive pre-Tertiary radiation of Neoaves. PMID:17148284

  10. Membrane curvature in cell biology: An integration of molecular mechanisms.

    PubMed

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists. PMID:27528656

  11. Display of travelling 3D scenes from single integral-imaging capture

    NASA Astrophysics Data System (ADS)

    Martinez-Corral, Manuel; Dorado, Adrian; Hong, Seok-Min; Sola-Pikabea, Jorge; Saavedra, Genaro

    2016-06-01

    Integral imaging (InI) is a 3D auto-stereoscopic technique that captures and displays 3D images. We present a method for easily projecting the information recorded with this technique by transforming the integral image into a plenoptic image, as well as choosing, at will, the field of view (FOV) and the focused plane of the displayed plenoptic image. Furthermore, with this method we can generate a sequence of images that simulates a camera travelling through the scene from a single integral image. The application of this method permits to improve the quality of 3D display images and videos.

  12. Integration of Mitochondrial Targeting for Molecular Cancer Therapeutics

    PubMed Central

    Marchetti, Philippe; Guerreschi, Pierre; Mortier, Laurent; Kluza, Jerome

    2015-01-01

    Mitochondrial metabolism greatly influences cancer cell survival, invasion, metastasis, and resistance to many anticancer drugs. Furthermore, molecular-targeted therapies (e.g., oncogenic kinase inhibitors) create a dependence of surviving cells on mitochondrial metabolism. For these reasons, inhibition of mitochondrial metabolism represents promising therapeutic pathways in cancer. This review provides an overview of mitochondrial metabolism in cancer and discusses the limitations of mitochondrial inhibition for cancer treatment. Finally, we present preclinical evidence that mitochondrial inhibition could be associated with oncogenic “drivers” inhibitors, which may lead to innovative drug combinations for improving the efficacy of molecular-targeted therapy. PMID:26713093

  13. Network integration and graph analysis in mammalian molecular systems biology

    PubMed Central

    Ma'ayan, A.

    2009-01-01

    Abstraction of intracellular biomolecular interactions into networks is useful for data integration and graph analysis. Network analysis tools facilitate predictions of novel functions for proteins, prediction of functional interactions and identification of intracellular modules. These efforts are linked with drug and phenotype data to accelerate drug-target and biomarker discovery. This review highlights the currently available varieties of mammalian biomolecular networks, and surveys methods and tools to construct, compare, integrate, visualise and analyse such networks. PMID:19045817

  14. In vivo, on-line monitoring of molecular response to photodynamic therapy: molecular imaging of vascular endothelial growth factor

    NASA Astrophysics Data System (ADS)

    Chang, Sung K.; Rizvi, Imran; Solban, Nicolas; Hasan, Tayyaba

    2007-02-01

    Cytokines are important messengers in cell-to-cell communications that regulate vital cellular and physiological processes, and play an important role in defining the diagnosis, prognosis and treatment response in various diseases. Although current ex vivo biochemical assays for cytokine quantitation are useful, their capabilities for studying dynamic cytokine expression in living systems are limited. Optical molecular imaging technology can help probe the spatiotemporal dynamics of cytokine expression in vivo and in real-time. We developed an in vivo optical molecular imaging strategy for monitoring one of these cytokines, the vascular endothelial growth factor (VEGF). With the imaging strategy, changes in tumoral VEGF concentration following cobalt chloride treatment and photodynamic therapy (PDT) were monitored. This was the first systematic study to test the feasibility of VEGF-targeted molecular imaging, and can potentially set the basis for online monitoring of cytokines that will help develop effective tools for diagnosis, prognosis, treatment planning and monitoring.

  15. Exploiting Molecular Biology by Time-Resolved Fluorescence Imaging

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

    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. PMID:26792102

  17. Molecular Images in Organic Chemistry: Assessment of Understanding in Aromaticity, Symmetry, Spectroscopy, and Shielding

    ERIC Educational Resources Information Center

    Ealy, Julie B.; Hermanson, Jim

    2006-01-01

    When students take General Chemistry there are substantially fewer molecular images than they will encounter in Organic Chemistry. The molecular images Organic Chemistry students see in their textbooks are ones that use dashes and wedges to represent 2D and semi 3D views, ball and spoke, ball and wire, and structural formulas, to name just a few.…

  18. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

    SciTech Connect

    Tim Schulze

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  19. Multiple time step integrators in ab initio molecular dynamics

    SciTech Connect

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

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

    NASA Astrophysics Data System (ADS)

    Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

    2010-05-01

    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 LaBr3(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 LaBr3(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.

  1. In vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging

    PubMed Central

    Hu, Zhenhua; Qu, Yawei; Wang, Kun; Zhang, Xiaojun; Zha, Jiali; Song, Tianming; Bao, Chengpeng; Liu, Haixiao; Wang, Zhongliang; Wang, Jing; Liu, Zhongyu; Liu, Haifeng; Tian, Jie

    2015-01-01

    Cerenkov luminescence imaging utilizes visible photons emitted from radiopharmaceuticals to achieve in vivo optical molecular-derived signals. Since Cerenkov radiation is weak, non-optimum for tissue penetration and continuous regardless of biological interactions, it is challenging to detect this signal with a diagnostic dose. Therefore, it is challenging to achieve useful activated optical imaging for the acquisition of direct molecular information. Here we introduce a novel imaging strategy, which converts γ and Cerenkov radiation from radioisotopes into fluorescence through europium oxide nanoparticles. After a series of imaging studies, we demonstrate that this approach provides strong optical signals with high signal-to-background ratios, an ideal tissue penetration spectrum and activatable imaging ability. In comparison with present imaging techniques, it detects tumour lesions with low radioactive tracer uptake or small tumour lesions more effectively. We believe it will facilitate the development of nuclear and optical molecular imaging for new, highly sensitive imaging applications. PMID:26123615

  2. In vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging.

    PubMed

    Hu, Zhenhua; Qu, Yawei; Wang, Kun; Zhang, Xiaojun; Zha, Jiali; Song, Tianming; Bao, Chengpeng; Liu, Haixiao; Wang, Zhongliang; Wang, Jing; Liu, Zhongyu; Liu, Haifeng; Tian, Jie

    2015-01-01

    Cerenkov luminescence imaging utilizes visible photons emitted from radiopharmaceuticals to achieve in vivo optical molecular-derived signals. Since Cerenkov radiation is weak, non-optimum for tissue penetration and continuous regardless of biological interactions, it is challenging to detect this signal with a diagnostic dose. Therefore, it is challenging to achieve useful activated optical imaging for the acquisition of direct molecular information. Here we introduce a novel imaging strategy, which converts γ and Cerenkov radiation from radioisotopes into fluorescence through europium oxide nanoparticles. After a series of imaging studies, we demonstrate that this approach provides strong optical signals with high signal-to-background ratios, an ideal tissue penetration spectrum and activatable imaging ability. In comparison with present imaging techniques, it detects tumour lesions with low radioactive tracer uptake or small tumour lesions more effectively. We believe it will facilitate the development of nuclear and optical molecular imaging for new, highly sensitive imaging applications. PMID:26123615

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

    SciTech Connect

    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. Double depth-enhanced 3D integral imaging in projection-type system without diffuser

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Jiao, Xiao-xue; Sun, Yu; Xie, Yan; Liu, Shao-peng

    2015-05-01

    Integral imaging is a three dimensional (3D) display technology without any additional equipment. A new system is proposed in this paper which consists of the elemental images of real images in real mode (RIRM) and the ones of virtual images in real mode (VIRM). The real images in real mode are the same as the conventional integral images. The virtual images in real mode are obtained by changing the coordinates of the corresponding points in elemental images which can be reconstructed by the lens array in virtual space. In order to reduce the spot size of the reconstructed images, the diffuser in conventional integral imaging is given up in the proposed method. Then the spot size is nearly 1/20 of that in the conventional system. And an optical integral imaging system is constructed to confirm that our proposed method opens a new way for the application of the passive 3D display technology.

  5. Tomographic Imaging of Molecular Orbitals in Length and Velocity Form

    SciTech Connect

    Zwan, Elmar V. van der; Lein, Manfred

    2007-11-29

    Recently Itatani et al. [Nature 432, 876 (2004)] introduced the new concept of molecular orbital tomography, where high harmonic generation (HHG) is used to image electronic wave functions. We describe an alternative reconstruction form, using momentum instead of dipole matrix elements for the electron recombination step in HHG. We show that using this velocity-form reconstruction, one obtains better results than using the original length-form reconstruction. We provide numerical evidence for our claim that one has to resort to extremely short pulses to perform the reconstruction for an orbital with arbitrary symmetry. The numerical evidence is based on the exact solution of the time-dependent Schroedinger equation for 2D model systems to simulate the experiment. Furthermore we show that in the case of cylindrically symmetric orbitals, such as the N{sub 2} orbital that was reconstructed in the original work, one can obtain the full 3D wave function and not only a 2D projection of it.

  6. Multicenter molecular integrals for Slater orbitals of higher principal quantum numbers

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    As was shown earlier by Tai (1979), by using the Fourier-transform technique and properly coupling a pair of two-center exchange integrals, the multicenter molecular integrals can be cast into a simple expression upon which numerical procedures can be directly applied. In this paper, the procedure of Tai is extended to integrals involving orbitals with arbitrarily higher principal quantum number. The derivation is outlined, and the explicit expressions are presented for a three-center nuclear attraction integral and a four-center two-electron Coulomb repulsion integral of arbitrary higher states.

  7. Intermolecular transfer integrals for organic molecular materials: can basis set convergence be achieved?

    NASA Astrophysics Data System (ADS)

    Huang, Jingsong; Kertesz, Miklos

    2004-05-01

    Intermolecular transfer integrals, and associated band-structures of organic molecular materials can be calculated through a dimer approach. Extensive numerical studies are performed on an ethylene π-dimer to investigate the basis sets dependence of transfer integrals. Convergence of calculated transfer integrals is achieved with respect to both Gaussian and plane-wave basis sets, provided the same level of theory is used. Effects of diffuse and polarization Gaussian functions on transfer integrals are identified. Comparison of experimental and theoretical values of transfer integrals of the TTF-TCNQ charge transfer salt is also presented.

  8. Accommodation response measurements for integral 3D image

    NASA Astrophysics Data System (ADS)

    Hiura, H.; Mishina, T.; Arai, J.; Iwadate, Y.

    2014-03-01

    We measured accommodation responses under integral photography (IP), binocular stereoscopic, and real object display conditions, and viewing conditions of binocular and monocular viewing conditions. The equipment we used was an optometric device and a 3D display. We developed the 3D display for IP and binocular stereoscopic images that comprises a high-resolution liquid crystal display (LCD) and a high-density lens array. The LCD has a resolution of 468 dpi and a diagonal size of 4.8 inches. The high-density lens array comprises 106 x 69 micro lenses that have a focal length of 3 mm and diameter of 1 mm. The lenses are arranged in a honeycomb pattern. The 3D display was positioned 60 cm from an observer under IP and binocular stereoscopic display conditions. The target was presented at eight depth positions relative to the 3D display: 15, 10, and 5 cm in front of the 3D display, on the 3D display panel, and 5, 10, 15 and 30 cm behind the 3D display under the IP and binocular stereoscopic display conditions. Under the real object display condition, the target was displayed on the 3D display panel, and the 3D display was placed at the eight positions. The results suggest that the IP image induced more natural accommodation responses compared to the binocular stereoscopic image. The accommodation responses of the IP image were weaker than those of a real object; however, they showed a similar tendency with those of the real object under the two viewing conditions. Therefore, IP can induce accommodation to the depth positions of 3D images.

  9. Scalable, Low-Noise Architecture for Integrated Terahertz Imagers

    NASA Astrophysics Data System (ADS)

    Gergelyi, Domonkos; Földesy, Péter; Zarándy, Ákos

    2015-06-01

    We propose a scalable, low-noise imager architecture for terahertz recordings that helps to build large-scale integrated arrays from any field-effect transistor (FET)- or HEMT-based terahertz detector. It enhances the signal-to-noise ratio (SNR) by inherently enabling complex sampling schemes. The distinguishing feature of the architecture is the serially connected detectors with electronically controllable photoresponse. We show that this architecture facilitate room temperature imaging by decreasing the low-noise amplifier (LNA) noise to one-sixteenth of a non-serial sensor while also reducing the number of multiplexed signals in the same proportion. The serially coupled architecture can be combined with the existing read-out circuit organizations to create high-resolution, coarse-grain sensor arrays. Besides, it adds the capability to suppress overall noise with increasing array size. The theoretical considerations are proven on a 4 by 4 detector array manufactured on 180 nm feature sized standard CMOS technology. The detector array is integrated with a low-noise AC-coupled amplifier of 40 dB gain and has a resonant peak at 460 GHz with 200 kV/W overall sensitivity.

  10. 40° image intensifier tubes in an integrated helmet system

    NASA Astrophysics Data System (ADS)

    Schreyer, Herbert; Boehm, Hans-Dieter V.; Svedevall, B.

    1993-12-01

    EUROCOPTER has been under contract to the French and German ministries of defence for five years to develop the TIGER, a second generation anti-tank helicopter. A piloting thermal imager has been installed on a steerable platform in the helicopter nose in order to achieve the possibility of flying round the clock. In addition to this sensor, which is sensitive at a wavelength of 10 micrometers , the German side has proposed using an Integrated Helmet System in the PAH 2. This helmet, manufactured by GEC-Marconi Avionics, incorporates two cathode ray tubes (CRT) and two image intensifier tubes which allow the pilot to use an additional sensor in the visible and near infrared spectrum. The electronic part will be built by Teldix. EUROCOPTER DEUTSCHLAND has received the first demonstrator of this helmet for testing in the EUROCOPTER Visionics Laboratory. Later, the C-prototype will be integrated into a BK 117 helicopter (AVT Avionik Versuchstrager). This new helmet has a field of view of 40 degree(s), and exit pupil of 15 mm and improved possibilities of adjusting the optical part. Laboratory tests have been carried out to test important parameters like optical resolution under low light level conditions, field of view, eye relief or exit pupil. The CRT channels have been tested for resolution, distortion, vignetting and homogeneity. The requirements and the properties of the helmet, test procedures and the results of these tests are presented in the paper.

  11. A knowledge-anchored integrative image search and retrieval system.

    PubMed

    Erdal, Selnur; Catalyurek, Umit V; Payne, Philip R O; Saltz, Joel; Kamal, Jyoti; Gurcan, Metin N

    2009-04-01

    Clinical data that may be used in a secondary capacity to support research activities are regularly stored in three significantly different formats: (1) structured, codified data elements; (2) semi-structured or unstructured narrative text; and (3) multi-modal images. In this manuscript, we will describe the design of a computational system that is intended to support the ontology-anchored query and integration of such data types from multiple source systems. Additional features of the described system include (1) the use of Grid services-based electronic data interchange models to enable the use of our system in multi-site settings and (2) the use of a software framework intended to address both potential security and patient confidentiality concerns that arise when transmitting or otherwise manipulating potentially privileged personal health information. We will frame our discussion within the specific experimental context of the concept-oriented query and integration of correlated structured data, narrative text, and images for cancer research. PMID:18040742

  12. Investigations on the Usefulness of CEACAMs as Potential Imaging Targets for Molecular Imaging Purposes

    PubMed Central

    Heine, Markus; Nollau, Peter; Masslo, Christoph; Nielsen, Peter; Freund, Barbara; Bruns, Oliver T.; Reimer, Rudolph; Hohenberg, Heinrich; Peldschus, Kersten; Ittrich, Harald; Schumacher, Udo

    2011-01-01

    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. PMID:22162753

  13. The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

    PubMed Central

    Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S

    2014-01-01

    Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm. PMID:24597512

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

    PubMed

    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. PMID:26061297

  15. Integration Of An MR Image Network Into A Clinical PACS

    NASA Astrophysics Data System (ADS)

    Ratib, Osman M.; Mankovich, Nicholas J.; Taira, Ricky K.; Cho, Paul S.; Huang, H. K.

    1988-06-01

    A direct link between a clinical pediatric PACS module and a FONAR MRI image network was implemented. The original MR network combines together the MR scanner, a remote viewing station and a central archiving station. The pediatric PACS directly connects to the archiving unit through an Ethernet TCP-IP network adhering to FONAR's protocol. The PACS communication software developed supports the transfer of patient studies and the patient information directly from the MR archive database to the pediatric PACS. In the first phase of our project we developed a package to transfer data between a VAX-111750 and the IBM PC I AT-based MR archive database through the Ethernet network. This system served as a model for PACS-to-modality network communication. Once testing was complete on this research network, the software and network hardware was moved to the clinical pediatric VAX for full PACS integration. In parallel to the direct transmission of digital images to the Pediatric PACS, a broadband communication system in video format was developed for real-time broadcasting of images originating from the MR console to 8 remote viewing stations distributed in the radiology department. These analog viewing stations allow the radiologists to directly monitor patient positioning and to select the scan levels during a patient examination from remote locations in the radiology department. This paper reports (1) the technical details of this implementation, (2) the merits of this network development scheme, and (3) the performance statistics of the network-to-PACS interface.

  16. Integrated imaging instrument for self-calibrated fluorescence protein microarrays

    NASA Astrophysics Data System (ADS)

    Reddington, A. P.; Monroe, M. R.; Ünlü, M. S.

    2013-10-01

    Protein microarrays, or multiplexed and high-throughput assays, monitor multiple protein binding events to facilitate the understanding of disease progression and cell physiology. Fluorescence imaging is a popular method to detect proteins captured by immobilized probes with high sensitivity and specificity. Reliability of fluorescence assays depends on achieving minimal inter- and intra-assay probe immobilization variation, an ongoing challenge for protein microarrays. Therefore, it is desirable to establish a label-free method to quantify the probe density prior to target incubation to calibrate the fluorescence readout. Previously, a silicon oxide on silicon chip design was introduced to enhance the fluorescence signal and enable interferometric imaging to self-calibrate the signal with the immobilized probe density. In this paper, an integrated interferometric reflectance imaging sensor and wide-field fluorescence instrument is introduced for sensitive and calibrated microarray measurements. This platform is able to analyze a 2.5 mm × 3.4 mm area, or 200 spots (100 μm diameter with 200 μm pitch), in a single field-of-view.

  17. Molecular Imaging of Transporters with Positron Emission Tomography

    NASA Astrophysics Data System (ADS)

    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

  18. JINN, an integrated software package for molecular geneticists.

    PubMed Central

    Johnsen, M

    1984-01-01

    I describe JINN, a microcomputer-based system designed to maintain and search a strain collection, to enter, modify and analyze sequences, and to use the EMBL Sequence Data Base. The major objective during development of this program has been integration of individual program modules to ensure a consistent and helpful user interface. The system is running under the CP/M operating system and requires little in the way of particular hardware configuration. PMID:6320101

  19. Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry

    PubMed Central

    Kuznetsov, Ilya; Filevich, Jorge; Dong, Feng; Woolston, Mark; Chao, Weilun; Anderson, Erik H.; Bernstein, Elliot R.; Crick, Dean C.; Rocca, Jorge J.; Menoni, Carmen S.

    2015-01-01

    Analytical probes capable of mapping molecular composition at the nanoscale are of critical importance to materials research, biology and medicine. Mass spectral imaging makes it possible to visualize the spatial organization of multiple molecular components at a sample's surface. However, it is challenging for mass spectral imaging to map molecular composition in three dimensions (3D) with submicron resolution. Here we describe a mass spectral imaging method that exploits the high 3D localization of absorbed extreme ultraviolet laser light and its fundamentally distinct interaction with matter to determine molecular composition from a volume as small as 50 zl in a single laser shot. Molecular imaging with a lateral resolution of 75 nm and a depth resolution of 20 nm is demonstrated. These results open opportunities to visualize chemical composition and chemical changes in 3D at the nanoscale. PMID:25903827

  20. Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems.

    PubMed

    Kamibayashi, Yuki; Miura, Shinichi

    2016-08-21

    In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction. PMID:27544094

  1. An Integrative Object-Based Image Analysis Workflow for Uav Images

    NASA Astrophysics Data System (ADS)

    Yu, Huai; Yan, Tianheng; Yang, Wen; Zheng, Hong

    2016-06-01

    In this work, we propose an integrative framework to process UAV images. The overall process can be viewed as a pipeline consisting of the geometric and radiometric corrections, subsequent panoramic mosaicking and hierarchical image segmentation for later Object Based Image Analysis (OBIA). More precisely, we first introduce an efficient image stitching algorithm after the geometric calibration and radiometric correction, which employs a fast feature extraction and matching by combining the local difference binary descriptor and the local sensitive hashing. We then use a Binary Partition Tree (BPT) representation for the large mosaicked panoramic image, which starts by the definition of an initial partition obtained by an over-segmentation algorithm, i.e., the simple linear iterative clustering (SLIC). Finally, we build an object-based hierarchical structure by fully considering the spectral and spatial information of the super-pixels and their topological relationships. Moreover, an optimal segmentation is obtained by filtering the complex hierarchies into simpler ones according to some criterions, such as the uniform homogeneity and semantic consistency. Experimental results on processing the post-seismic UAV images of the 2013 Ya'an earthquake demonstrate the effectiveness and efficiency of our proposed method.

  2. Integrating genomics, proteomics and bioinformatics in translational studies of molecular medicine.

    PubMed

    Ostrowski, Jerzy; Wyrwicz, Lucjan S

    2009-09-01

    Understanding the molecular mechanisms of disease requires the introduction of molecular diagnostics into medical practice. Current medicine employs only elements of molecular diagnostics, which are usually applied on the scale of single genes. Medicine in the postgenomic era will utilize thousands of disease-associated molecular markers provided by high-throughput sequencing and functional genomic, proteomic and metabolomic studies. Such a spectrum of techniques will link clinical medicine based on molecularly oriented diagnostics with the prediction and prevention of disease. To achieve this task, large-scale and genome-wide biological and medical data must be combined with biostatistical and bioinformatic analyses to model biological systems. Collecting, cataloging and comparing data from molecular studies, and the subsequent development of conclusions, creates the fundamentals of systems biology. This highly complex analytical process reflects a new scientific paradigm known as integrative genomics. PMID:19732006

  3. Integrative genomics--a basic and essential tool for the development of molecular medicine.

    PubMed

    Ostrowski, Jerzy

    2008-01-01

    Understanding the molecular mechanisms of disease requires the introduction of molecular diagnostics into medical practice. Current medicine employs only elements of molecular diagnostics, and usually on the scale of single genes. Medicine in the post-genomic era will utilize thousands of molecular markers associated with disease that are provided by high-throughput sequencing and functional genomic, proteomic and metabolomic studies. Such a spectrum of techniques will link clinical medicine based on molecularly oriented diagnostics with the prediction and prevention of disease. To achieve this task, large-scale and genome-wide biological and medical data must be combined with biostatistical analyses and bioinformatic modeling of biological systems. The collecting, cataloging and comparison of data from molecular studies and the subsequent development of conclusions create the fundamentals of systems biology. This highly complex analytical process reflects a new scientific paradigm called integrative genomics. PMID:19172842

  4. Three-dimensional visualization of objects in scattering medium using integral imaging and spectral analysis

    NASA Astrophysics Data System (ADS)

    Lee, Yeonkyung; Yoo, Hoon

    2016-02-01

    This paper presents a three-dimensional visualization method of 3D objects in a scattering medium. The proposed method employs integral imaging and spectral analysis to improve the visual quality of 3D images. The images observed from 3D objects in the scattering medium such as turbid water suffer from image degradation due to scattering. The main reason is that the observed image signal is very weak compared with the scattering signal. Common image enhancement techniques including histogram equalization and contrast enhancement works improperly to overcome the problem. Thus, integral imaging that enables to integrate the weak signals from multiple images was discussed to improve image quality. In this paper, we apply spectral analysis to an integral imaging system such as the computational integral imaging reconstruction. Also, we introduce a signal model with a visibility parameter to analyze the scattering signal. The proposed method based on spectral analysis efficiently estimates the original signal and it is applied to elemental images. The visibility-enhanced elemental images are then used to reconstruct 3D images using a computational integral imaging reconstruction algorithm. To evaluate the proposed method, we perform the optical experiments for 3D objects in turbid water. The experimental results indicate that the proposed method outperforms the existing methods.

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

    PubMed Central

    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

  6. Balancing an accurate representation of the molecular surface in generalized born formalisms with integrator stability in molecular dynamics simulations.

    PubMed

    Chocholousová, Jana; Feig, Michael

    2006-04-30

    Different integrator time steps in NVT and NVE simulations of protein and nucleic acid systems are tested with the GBMV (Generalized Born using Molecular Volume) and GBSW (Generalized Born with simple SWitching) methods. The simulation stability and energy conservation is investigated in relation to the agreement with the Poisson theory. It is found that very close agreement between generalized Born methods and the Poisson theory based on the commonly used sharp molecular surface definition results in energy drift and simulation artifacts in molecular dynamics simulation protocols with standard 2-fs time steps. New parameters are proposed for the GBMV method, which maintains very good agreement with the Poisson theory while providing energy conservation and stable simulations at time steps of 1 to 1.5 fs. PMID:16518883

  7. The Graduate Training Programme "Molecular Imaging for the Analysis of Gene and Protein Expression": A Case Study with an Insight into the Participation of Universities of Applied Sciences

    ERIC Educational Resources Information Center

    Hafner, Mathias

    2008-01-01

    Cell biology and molecular imaging technologies have made enormous progress in basic research. However, the transfer of this knowledge to the pharmaceutical drug discovery process, or even therapeutic improvements for disorders such as neuronal diseases, is still in its infancy. This transfer needs scientists who can integrate basic research with…

  8. Semantic Integrative Digital Pathology: Insights into Microsemiological Semantics and Image Analysis Scalability.

    PubMed

    Racoceanu, Daniel; Capron, Frédérique

    2016-01-01

    Being able to provide a traceable and dynamic second opinion has become an ethical priority for patients and health care professionals in modern computer-aided medicine. In this perspective, a semantic cognitive virtual microscopy approach has been recently initiated, the MICO project, by focusing on cognitive digital pathology. This approach supports the elaboration of pathology-compliant daily protocols dedicated to breast cancer grading, in particular mitotic counts and nuclear atypia. A proof of concept has thus been elaborated, and an extension of these approaches is now underway in a collaborative digital pathology framework, the FlexMIm project. As important milestones on the way to routine digital pathology, a series of pioneer international benchmarking initiatives have been launched for mitosis detection (MITOS), nuclear atypia grading (MITOS-ATYPIA) and glandular structure detection (GlaS), some of the fundamental grading components in diagnosis and prognosis. These initiatives allow envisaging a consolidated validation referential database for digital pathology in the very near future. This reference database will need coordinated efforts from all major teams working in this area worldwide, and it will certainly represent a critical bottleneck for the acceptance of all future imaging modules in clinical practice. In line with recent advances in molecular imaging and genetics, keeping the microscopic modality at the core of future digital systems in pathology is fundamental to insure the acceptance of these new technologies, as well as for a deeper systemic, structured comprehension of the pathologies. After all, at the scale of routine whole-slide imaging (WSI; ∼0.22 µm/pixel), the microscopic image represents a structured 'genomic cluster', enabling a naturally structured support for integrative digital pathology approaches. In order to accelerate and structure the integration of this heterogeneous information, a major effort is and will continue to

  9. Integrated photoacoustic, ultrasound and fluorescence platform for diagnostic medical imaging-proof of concept study with a tissue mimicking phantom

    PubMed Central

    James, Joseph; Murukeshan, Vadakke Matham; Woh, Lye Sun

    2014-01-01

    The structural and molecular heterogeneities of biological tissues demand the interrogation of the samples with multiple energy sources and provide visualization capabilities at varying spatial resolution and depth scales for obtaining complementary diagnostic information. A novel multi-modal imaging approach that uses optical and acoustic energies to perform photoacoustic, ultrasound and fluorescence imaging at multiple resolution scales from the tissue surface and depth is proposed in this paper. The system comprises of two distinct forms of hardware level integration so as to have an integrated imaging system under a single instrumentation set-up. The experimental studies show that the system is capable of mapping high resolution fluorescence signatures from the surface, optical absorption and acoustic heterogeneities along the depth (>2cm) of the tissue at multi-scale resolution (<1µm to <0.5mm). PMID:25071954

  10. Performances of compact integrated superconducting magnetometers for biomagnetic imaging

    NASA Astrophysics Data System (ADS)

    Granata, C.; Vettoliere, A.; Rombetto, S.; Nappi, C.; Russo, M.

    2008-10-01

    In the present paper, performances of compact fully integrated superconducting quantum interference device (SQUID) magnetometers, recently developed, have been investigated in view of their employment in large multichannel systems for biomagnetic imaging. The analysis has been focused on SQUID sensors having a pickup loop side length of 3 and 4 mm based on a design aimed to maximize the magnetic flux transferred from the detection coil to the SQUID in comparison with a magnetometer with 9 mm side length having a suitable sensitivity for biomagnetic applications. The performance study has been consisted in the computation of the magnetic responses to a current dipole which is the most fundamental approach used in biomagnetism. The results have shown that the dipole current sensitivity of 4 mm long side compact magnetometers is suitable for application in multichannel systems for magnetoencephalography and magnetocardiography.

  11. Integrative molecular characterization of head and neck cancer cell model genomes

    PubMed Central

    Tsui, Ivy F.L.; Garnis, Cathie

    2010-01-01

    Background Cell lines are invaluable model systems for the investigation of cancer. Knowledge of the molecular alterations that exist within cell models is required to define the mechanisms governing cellular phenotypes. Methods Five tongue squamous cell carcinomas cell lines and one submaxillary salivary gland epidermoid carcinoma cell line were analyzed for copy number and mRNA expression by tiling-path DNA microarrays and Agilent Whole Human Genome Oligoarrays, respectively. Results Integrative analysis of genetic and expression alterations revealed the molecular landscape of each cell line. Molecular results for individual cell lines and across all samples have been summarized and made available for easy reference. Conclusion Our integrative genomic analyses have defined the DNA and RNA alterations for each individual line. These data will be useful to anyone modelling oral cancer behaviour, providing a molecular context that will be useful for deciphering cell phenotypes. PMID:20014447

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

    PubMed Central

    Lu, Feng-Mei

    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 neuroscience has provided tremendous insights into disturbed human brain function. Among all of the molecular imaging modalities, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have occupied a particular position that visualize and measure the physiological processes using high-affinity and high-specificity molecular radioactive tracers as imaging probes in intact living brain. In this review, we will put emphasis on the PET/SPECT applications in Alzheimer’s disease (AD) and Parkinson’s disease (PD) as major CNS disorders. We will first give an overview of the main classical molecular neuroimaging modalities. Then, the major clinical applications of PET and SPECT along with molecular probes in the fields of psychiatry and neurology will be discussed. PMID:26029646

  13. Molecular clock integration of brown adipose tissue formation and function

    PubMed Central

    Nam, Deokhwa; Yechoor, Vijay K.; Ma, Ke

    2016-01-01

    Abstract The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  14. Molecular clock integration of brown adipose tissue formation and function.

    PubMed

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  15. Application of integral imaging autostereoscopic display to medical training equipment

    NASA Astrophysics Data System (ADS)

    Nagatani, Hiroyuki

    2010-02-01

    We applied an autostereoscopic display based on the integral imaging method (II method) to training equipment for medical treatment in an attempt to recover the binocular vision performance of strabismus or amblyopia (lazy eye) patients. This report summarizes the application method and results. The point of the training is to recognize the parallax using both eyes. The strabismus or amblyopia patients have to recognize the information on both eyes equally when they gaze at the display with parallax and perceive the stereo depth of the content. Participants in this interactive training engage actively with the image. As a result, they are able to revive their binocular visual function while playing a game. Through the training, the observers became able to recognize the amount of parallax correctly. In addition, the training level can be changed according to the eyesight difference between a right eye and a left eye. As a result, we ascertained that practical application of the II method for strabismus or amblyopia patients would be possible.

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

    PubMed Central

    Meng, Qingqing; Li, Zheng

    2013-01-01

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

  17. Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT.

    PubMed

    Kirmizialtin, Serdal; Hennelly, Scott P; Schug, Alexander; Onuchic, Jose N; Sanbonmatsu, Karissa Y

    2015-01-01

    Integration and calibration of molecular dynamics simulations with experimental data remain a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2'-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the force field according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations. PMID:25726467

  18. Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT

    PubMed Central

    Kirmizialtin, Serdal; Hennelly, Scott P.; Schug, Alexander; Onuchic, Jose N.; Sanbonmatsu, Karissa Y.

    2016-01-01

    Integration and calibration of molecular dynamics simulations with experimental data remains a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2’-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the forcefield according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations. PMID:25726467

  19. Investigating Atmospheric Oxidation with Molecular Dynamics Imaging and Spectroscopy

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    PubMed Central

    2014-01-01

    Background In an effort to reduce necessary acquisition time to perform molecular breast imaging (MBI), we compared diagnostic performance of MBI performed with standard 10-min-per-view acquisitions and half-time 5-min-per-view acquisitions, with and without wide beam reconstruction (WBR) processing. Methods Eighty-two bilateral, two-view MBI studies were reviewed. Studies were performed with 300 MBq Tc-99 m sestamibi and a direct conversion molecular breast imaging (DC-MBI) system. Acquisitions were 10 min-per-view; the first half of each was extracted to create 5-min-per-view datasets, and WBR processing was applied. The 10-min-, 5-min-, and 5-min-per-view WBR studies were independently interpreted in a randomized, blinded fashion by two radiologists. Assessments of 1 to 5 were assigned; 4 and 5 were considered test positive. Background parenchymal uptake, lesion type, distribution of non-mass lesions, lesion intensity, and image quality were described. Results Considering detection of all malignant and benign lesions, 5 min-per-view MBI had lower sensitivity (mean of 70% vs. 85% (p ≤ 0.04) for two readers) and lower area under curve (AUC) (mean of 92.7 vs. 99.6, p ≤ 0.01) but had similar specificity (p = 1.0). WBR processing did not alter sensitivity, specificity, or AUC obtained at 5 min-per-view. Overall agreement in final assessment between 5-min-per-view and 10-min-per-view acquisition types was near perfect (κ = 0.82 to 0.89); however, fair to moderate agreement was observed for assessment category 3 (probably benign) (κ = 0.24 to 0.48). Of 33 malignant lesions, 6 (18%) were changed from assessment of 4 or 5 with 10-min-per-view MBI to assessment of 3 with 5-min-per-view MBI. Image quality of 5-min-per-view studies was reduced compared to 10-min-per-view studies for both readers (3.24 vs. 3.98, p < 0.0001 and 3.60 vs. 3.91, p < 0.0001). WBR processing improved image quality for one reader (3.85 vs. 3.24, p < 0

  1. Integrated molecular mechanism directing nucleosome reorganization by human FACT

    PubMed Central

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-01-01

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT–histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3–H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid–H2A steric collision on the H2A-docking surface of the H3–H4 tetramer within the nucleosome induces H2A–H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  2. Integrated molecular mechanism directing nucleosome reorganization by human FACT.

    PubMed

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-03-15

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT-histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3-H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid-H2A steric collision on the H2A-docking surface of the H3-H4 tetramer within the nucleosome induces H2A-H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  3. Establishment of functional and molecular ultrasound for breast cancer xenograft imaging.

    PubMed

    Bzyl, J

    2014-04-01

    The present work was originally published in European Radiology and as a PhD thesis at the RWTH Aachen University and was conducted at the Institute for Experimental Molecular Imaging at the RWTH Aachen University. PMID:24683170

  4. Semiconducting Polymer Nanoparticles as Photoacoustic Molecular Imaging Probes in Living Mice

    PubMed Central

    Pu, Kanyi; Shuhendler, Adam J.; Jokerst, Jesse V.; Mei, Jianguo; Gambhir, Sanjiv S.; Bao, Zhenan; Rao, Jianghong

    2014-01-01

    Photoacoustic (PA) imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, PA molecular imaging probes have to be developed. Herein we introduce near infrared (NIR) light absorbing semiconducting polymer nanoparticles (SPNs) as a new class of contrast agents for PA molecular imaging. SPNs can produce stronger signal than commonly used single-wall carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph node PA mapping in living mice at a low systematic injection mass. Furthermore, SPNs possess high structural flexibility, narrow PA spectral profiles, and strong resistance to photodegradation and oxidation, which enables development of the first NIR ratiometric PA probe for in vivo real-time imaging of reactive oxygen species—vital chemical mediators of many diseases. These results demonstrate SPNs an ideal nanoplatform for developing PA molecular probes. PMID:24463363

  5. Integrative systems medicine approaches to identify molecular targets in lymphoid malignancies.

    PubMed

    Frazzi, Raffaele; Auffray, Charles; Ferrari, Angela; Filippini, Perla; Rutella, Sergio; Cesario, Alfredo

    2016-01-01

    Although survival rates for lymphoproliferative disorders are steadily increasing both in the US and in Europe, there is need for optimizing front-line therapies and developing more effective salvage strategies. Recent advances in molecular genetics have highlighted the biological diversity of lymphoproliferative disorders. In particular, integrative approaches including whole genome sequencing, whole exome sequencing, and transcriptome or RNA sequencing have been instrumental to the identification of molecular targets for treatment. Herein, we will discuss how genomic, epigenomic and proteomic approaches in lymphoproliferative disorders have supported the discovery of molecular lesions and their therapeutic targeting in the clinic. PMID:27580852

  6. High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates

    PubMed Central

    Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S.; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

    2014-01-01

    In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research. PMID:25098236

  7. Images of a lipid bilayer at molecular resolution by scanning tunneling microscopy.

    PubMed Central

    Smith, D P; Bryant, A; Quate, C F; Rabe, J P; Gerber, C; Swalen, J D

    1987-01-01

    The molecular structure of a fatty acid bilayer has been recorded with a scanning tunneling microscope operating in air. The molecular film, a bilayer of cadmium icosanoate (arachidate), was deposited onto a graphite substrate by the Langmuir-Blodgett technique. The packing of the lipid film was found to be partially ordered. Along one axis of the triclinic unit cell the intermolecular distance varied randomly around a mean of 5.84 A with a SD of 0.24 A. Along the other axis the mean distance was 4.1 A and appeared to vary monotonically over several intermolecular distances, indicating that a superstructure of longer range may exist. The molecular density was one molecular per 19.4 A2. The surprising ability of the scanning tunneling microscope to image the individual molecular chains demonstrates that electrons from the graphite can be transferred along the molecular chains for a distance of 50 A. Images PMID:3103128

  8. Transmission imaging for integrated PET-MR systems

    NASA Astrophysics Data System (ADS)

    Bowen, Spencer L.; Fuin, Niccolò; Levine, Michael A.; Catana, Ciprian

    2016-08-01

    Attenuation correction for PET-MR systems continues to be a challenging problem, particularly for body regions outside the head. The simultaneous acquisition of transmission scan based μ-maps and MR images on integrated PET-MR systems may significantly increase the performance of and offer validation for new MR-based μ-map algorithms. For the Biograph mMR (Siemens Healthcare), however, use of conventional transmission schemes is not practical as the patient table and relatively small diameter scanner bore significantly restrict radioactive source motion and limit source placement. We propose a method for emission-free coincidence transmission imaging on the Biograph mMR. The intended application is not for routine subject imaging, but rather to improve and validate MR-based μ-map algorithms; particularly for patient implant and scanner hardware attenuation correction. In this study we optimized source geometry and assessed the method’s performance with Monte Carlo simulations and phantom scans. We utilized a Bayesian reconstruction algorithm, which directly generates μ-map estimates from multiple bed positions, combined with a robust scatter correction method. For simulations with a pelvis phantom a single torus produced peak noise equivalent count rates (34.8 kcps) dramatically larger than a full axial length ring (11.32 kcps) and conventional rotating source configurations. Bias in reconstructed μ-maps for head and pelvis simulations was  ⩽4% for soft tissue and  ⩽11% for bone ROIs. An implementation of the single torus source was filled with 18F-fluorodeoxyglucose and the proposed method quantified for several test cases alone or in comparison with CT-derived μ-maps. A volume average of 0.095 cm‑1 was recorded for an experimental uniform cylinder phantom scan, while a bias of  <2% was measured for the cortical bone equivalent insert of the multi-compartment phantom. Single torus μ-maps of a hip implant phantom showed significantly

  9. Transmission imaging for integrated PET-MR systems.

    PubMed

    Bowen, Spencer L; Fuin, Niccolò; Levine, Michael A; Catana, Ciprian

    2016-08-01

    Attenuation correction for PET-MR systems continues to be a challenging problem, particularly for body regions outside the head. The simultaneous acquisition of transmission scan based μ-maps and MR images on integrated PET-MR systems may significantly increase the performance of and offer validation for new MR-based μ-map algorithms. For the Biograph mMR (Siemens Healthcare), however, use of conventional transmission schemes is not practical as the patient table and relatively small diameter scanner bore significantly restrict radioactive source motion and limit source placement. We propose a method for emission-free coincidence transmission imaging on the Biograph mMR. The intended application is not for routine subject imaging, but rather to improve and validate MR-based μ-map algorithms; particularly for patient implant and scanner hardware attenuation correction. In this study we optimized source geometry and assessed the method's performance with Monte Carlo simulations and phantom scans. We utilized a Bayesian reconstruction algorithm, which directly generates μ-map estimates from multiple bed positions, combined with a robust scatter correction method. For simulations with a pelvis phantom a single torus produced peak noise equivalent count rates (34.8 kcps) dramatically larger than a full axial length ring (11.32 kcps) and conventional rotating source configurations. Bias in reconstructed μ-maps for head and pelvis simulations was  ⩽4% for soft tissue and  ⩽11% for bone ROIs. An implementation of the single torus source was filled with (18)F-fluorodeoxyglucose and the proposed method quantified for several test cases alone or in comparison with CT-derived μ-maps. A volume average of 0.095 cm(-1) was recorded for an experimental uniform cylinder phantom scan, while a bias of  <2% was measured for the cortical bone equivalent insert of the multi-compartment phantom. Single torus μ-maps of a hip implant phantom showed significantly

  10. Achieving molecular selectivity in imaging using multiphoton Raman spectroscopy techniques

    SciTech Connect

    Holtom, Gary R. ); Thrall, Brian D. ); Chin, Beek Yoke ); Wiley, H Steven ); Colson, Steven D. )

    2000-12-01

    In the case of most imaging methods, contrast is generated either by physical properties of the sample (Differential Image Contrast, Phase Contrast), or by fluorescent labels that are localized to a particular protein or organelle. Standard Raman and infrared methods for obtaining images are based upon the intrinsic vibrational properties of molecules, and thus obviate the need for attached flurophores. Unfortunately, they have significant limitations for live-cell imaging. However, an active Raman method, called Coherent Anti-Stokes Raman Scattering (CARS), is well suited for microscopy, and provides a new means for imaging specific molecules. Vibrational imaging techniques, such as CARS, avoid problems associated with photobleaching and photo-induced toxicity often associated with the use of fluorescent labels with live cells. Because the laser configuration needed to implement CARS technology is similar to that used in other multiphoton microscopy methods, such as two -photon fluorescence and harmonic generation, it is possible to combine imaging modalities, thus generating simultaneous CARS and fluorescence images. A particularly powerful aspect of CARS microscopy is its ability to selectively image deuterated compounds, thus allowing the visualization of molecules, such as lipids, that are chemically indistinguishable from the native species.

  11. Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.

    PubMed

    Pan, Ying; Volkmer, Jens-Peter; Mach, Kathleen E; Rouse, Robert V; Liu, Jen-Jane; Sahoo, Debashis; Chang, Timothy C; Metzner, Thomas J; Kang, Lei; van de Rijn, Matt; Skinner, Eila C; Gambhir, Sanjiv S; Weissman, Irving L; Liao, Joseph C

    2014-10-29

    A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer. PMID:25355698

  12. A unified scheme for the calculation of differentiated and undifferentiated molecular integrals over solid-harmonic Gaussians.

    PubMed

    Reine, Simen; Tellgren, Erik; Helgaker, Trygve

    2007-09-14

    Utilizing the fact that solid-harmonic combinations of Cartesian and Hermite Gaussian atomic orbitals are identical, a new scheme for the evaluation of molecular integrals over solid-harmonic atomic orbitals is presented, where the integration is carried out over Hermite rather than Cartesian atomic orbitals. Since Hermite Gaussians are defined as derivatives of spherical Gaussians, the corresponding molecular integrals become the derivatives of integrals over spherical Gaussians, whose transformation to the solid-harmonic basis is performed in the same manner as for integrals over Cartesian Gaussians, using the same expansion coefficients. The presented solid-harmonic Hermite scheme simplifies the evaluation of derivative molecular integrals, since differentiation by nuclear coordinates merely increments the Hermite quantum numbers, thereby providing a unified scheme for undifferentiated and differentiated four-center molecular integrals. For two- and three-center two-electron integrals, the solid-harmonic Hermite scheme is particularly efficient, significantly reducing the cost relative to the Cartesian scheme. PMID:17712455

  13. Small unilamellar vesicles: a platform technology for molecular imaging of brain tumors

    NASA Astrophysics Data System (ADS)

    Iqbal, Umar; Albaghdadi, Homam; Nieh, Mu-Ping; Tuor, Ursula I.; Mester, Zoltan; Stanimirovic, Danica; Katsaras, John; Abulrob, Abedelnasser

    2011-05-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  14. Small Unilamellar Vesicles: A Platform Technology for Molecular Imaging of Brain Tumors

    SciTech Connect

    Iqbal, U; Albaghdadi, H; Nieh, Mu-Ping; Tuor, U.I; Mester, Z; Stanimirovic, D; Katsaras, John; Abulrob, A

    2011-01-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  15. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    DOE PAGESBeta

    Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; et al

    2016-02-02

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

  16. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    PubMed

    Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-16

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

  17. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    PubMed Central

    Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

    2016-01-01

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

  18. Deblurring molecular images using desorption electrospray ionization mass spectrometry

    PubMed Central

    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

  19. Improvements of 3-D image quality in integral display by reducing distortion errors

    NASA Astrophysics Data System (ADS)

    Kawakita, Masahiro; Sasaki, Hisayuki; Arai, Jun; Okano, Fumio; Suehiro, Koya; Haino, Yasuyuki; Yoshimura, Makoto; Sato, Masahito

    2008-02-01

    An integral three-dimensional (3-D) system based on the principle of integral photography can display natural 3-D images. We studied ways of improving the resolution and viewing angle of 3-D images by using extremely highresolution (EHR) video in an integral 3-D video system. One of the problems with the EHR projection-type integral 3-D system is that positional errors appear between the elemental image and the elemental lens when there is geometric distortion in the projected image. We analyzed the relationships between the geometric distortion in the elemental images caused by the projection lens and the spatial distortion of the reconstructed 3-D image. As a result, we clarified that 3-D images reconstructed far from the lens array were greatly affected by the distortion of the elemental images, and that the 3-D images were significantly distorted in the depth direction at the corners of the displayed images. Moreover, we developed a video signal processor that electrically compensated the distortion in the elemental images for an EHR projection-type integral 3-D system. Therefore, the distortion in the displayed 3-D image was removed, and the viewing angle of the 3-D image was expanded to nearly double that obtained with the previous prototype system.

  20. IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface

    PubMed Central

    2012-01-01

    Background The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed. Results A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform. Conclusions IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at http://kyc.nenu.edu.cn/IVSPlat/. PMID:22222098

  1. Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis.

    PubMed

    Zhao, Zide; Zhang, Yingying; Gai, Fengchun; Wang, Ying

    2016-09-01

    Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P‑values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention. PMID:27430657

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

    PubMed

    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

  3. NEAR-INFRARED DYES: Probe Development and Applications in Optical Molecular Imaging

    PubMed Central

    Nolting, Donald D.; Gore, John C.; Pham, Wellington

    2010-01-01

    The recent emergence of optical imaging has brought forth a unique challenge for chemists: development of new biocompatible dyes that fluoresce in the near-infrared (NIR) region for optimal use in biomedical applications. This review describes the synthesis of NIR dyes and the design of probes capable of noninvasively imaging molecular events in small animal models. PMID:21822405

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

    PubMed

    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. PMID:25324995

  5. Imaging Ultra-fast Molecular Dynamics in Free Electron Laser Field

    NASA Astrophysics Data System (ADS)

    Zhang, Y. Z.; Jiang, Y. H.

    The free electron laser (FEL) provides the coherent, brilliant and ultrashort light pulse in short wavelength (extreme ultraviolet and X-ray) regimes, opening up possibilities to study ultra-fast molecular dynamics in photo-induced chemical reactions with new methodologies. In this chapter, we introduce the time-resolved pump-probe experiments on gas-phase targets with FEL facilities to image the nuclear and electronic motions in molecular reactions, which serve as a benchmark for further FEL applications like coherent diffraction imaging and coherent control of functional dynamics in complex molecular reactions.

  6. Advances in molecular imaging: targeted optical contrast agents for cancer diagnostics

    PubMed Central

    Hellebust, Anne; Richards-Kortum, Rebecca

    2012-01-01

    Over the last three decades, our understanding of the molecular changes associated with cancer development and progression has advanced greatly. This has led to new cancer therapeutics targeted against specific molecular pathways; such therapies show great promise to reduce mortality, in part by enabling physicians to tailor therapy for patients based on a molecular profile of their tumor. Unfortunately, the tools for definitive cancer diagnosis – light microscopic examination of biopsied tissue stained with nonspecific dyes – remain focused on the analysis of tissue ex vivo. There is an important need for new clinical tools to support the molecular diagnosis of cancer. Optical molecular imaging is emerging as a technique to help meet this need. Targeted, optically active contrast agents can specifically label extra-and intracellular biomarkers of cancer. Optical images can be acquired in real time with high spatial resolution to image-specific molecular targets, while still providing morphologic context. This article reviews recent advances in optical molecular imaging, highlighting the advances in technology required to improve early cancer detection, guide selection of targeted therapy and rapidly evaluate therapeutic efficacy. PMID:22385200

  7. Fluorescence molecular tomographic image reconstruction based on reduced measurement data

    NASA Astrophysics Data System (ADS)

    Zou, Wei; Wang, Jiajun; Feng, David Dagan; Fang, Erxi

    2015-07-01

    The analysis of fluorescence molecular tomography is important for medical diagnosis and treatment. Although the quality of reconstructed results can be improved with the increasing number of measurement data, the scale of the matrices involved in the reconstruction of fluorescence molecular tomography will also become larger, which may slow down the reconstruction process. A new method is proposed where measurement data are reduced according to the rows of the Jacobian matrix and the projection residual error. To further accelerate the reconstruction process, the global inverse problem is solved with level-by-level Schur complement decomposition. Simulation results demonstrate that the speed of the reconstruction process can be improved with the proposed algorithm.

  8. Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging.

    PubMed

    Sharifi, Shahriar; Seyednejad, Hajar; Laurent, Sophie; Atyabi, Fatemeh; Saei, Amir Ata; Mahmoudi, Morteza

    2015-01-01

    In the last decade, the biomedical applications of nanoparticles (NPs) (e.g. cell tracking, biosensing, magnetic resonance imaging (MRI), targeted drug delivery, and tissue engineering) have been increasingly developed. Among the various NP types, superparamagnetic iron oxide NPs (SPIONs) have attracted considerable attention for early detection of diseases due to their specific physicochemical properties and their molecular imaging capabilities. A comprehensive review is presented on the recent advances in the development of in vitro and in vivo SPION applications for molecular imaging, along with opportunities and challenges. PMID:25882768

  9. A novel method for image denoising of fluorescence molecular imaging based on fuzzy C-Means clustering

    NASA Astrophysics Data System (ADS)

    An, Yu; Liu, Jie; Ye, Jinzuo; Mao, Yamin; Yang, Xin; Jiang, Shixin; Chi, Chongwei; Tian, Jie

    2015-03-01

    As an important molecular imaging modality, fluorescence molecular imaging (FMI) has the advantages of high sensitivity, low cost and ease of use. By labeling the regions of interest with fluorophore, FMI can noninvasively obtain the distribution of fluorophore in-vivo. However, due to the fact that the spectrum of fluorescence is in the section of the visible light range, there are mass of autofluorescence on the surface of the bio-tissues, which is a major disturbing factor in FMI. Meanwhile, the high-level of dark current for charge-coupled device (CCD) camera and other influencing factor can also produce a lot of background noise. In this paper, a novel method for image denoising of FMI based on fuzzy C-Means clustering (FCM) is proposed, because the fluorescent signal is the major component of the fluorescence images, and the intensity of autofluorescence and other background signals is relatively lower than the fluorescence signal. First, the fluorescence image is smoothed by sliding-neighborhood operations to initially eliminate the noise. Then, the wavelet transform (WLT) is performed on the fluorescence images to obtain the major component of the fluorescent signals. After that, the FCM method is adopt to separate the major component and background of the fluorescence images. Finally, the proposed method was validated using the original data obtained by in vivo implanted fluorophore experiment, and the results show that our proposed method can effectively obtain the fluorescence signal while eliminate the background noise, which could increase the quality of fluorescence images.

  10. Intraparticle Molecular Orbital Engineering of Semiconducting Polymer Nanoparticles as Amplified Theranostics for in Vivo Photoacoustic Imaging and Photothermal Therapy.

    PubMed

    Lyu, Yan; Fang, Yuan; Miao, Qingqing; Zhen, Xu; Ding, Dan; Pu, Kanyi

    2016-04-26

    Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems. PMID:26959505

  11. Method and apparatus for molecular imaging using x-rays at resonance wavelengths

    DOEpatents

    Chapline, G.F. Jr.

    Holographic x-ray images are produced representing the molecular structure of a microscopic object, such as a living cell, by directing a beam of coherent x-rays upon the object to produce scattering of the x-rays by the object, producing interference on a recording medium between the scattered x-rays from the object and unscattered coherent x-rays and thereby producing holograms on the recording surface, and establishing the wavelength of the coherent x-rays to correspond with a molecular resonance of a constituent of such object and thereby greatly improving the contrast, sensitivity and resolution of the holograms as representations of molecular structures involving such constituent. For example, the coherent x-rays may be adjusted to the molecular resonant absorption line of nitrogen at about 401.3 eV to produce holographic images featuring molecular structures involving nitrogen.

  12. Method and apparatus for molecular imaging using X-rays at resonance wavelengths

    DOEpatents

    Chapline, Jr., George F.

    1985-01-01

    Holographic X-ray images are produced representing the molecular structure of a microscopic object, such as a living cell, by directing a beam of coherent X-rays upon the object to produce scattering of the X-rays by the object, producing interference on a recording medium between the scattered X-rays from the object and unscattered coherent X-rays and thereby producing holograms on the recording surface, and establishing the wavelength of the coherent X-rays to correspond with a molecular resonance of a constituent of such object and thereby greatly improving the contrast, sensitivity and resolution of the holograms as representations of molecular structures involving such constituent. For example, the coherent X-rays may be adjusted to the molecular resonant absorption line of nitrogen at about 401.3 eV to produce holographic images featuring molecular structures involving nitrogen.

  13. Print and Image Integration of Science Texts and Reading Comprehension: A Systemic Functional Linguistics Perspective

    ERIC Educational Resources Information Center

    Hsu, Pei-Ling; Yang, Wen-Gin

    2007-01-01

    Systemic functional linguistics (SFL) was the foundation for this study that explored the effect of science text and image integration on grade 9 students' reading comprehension. Two texts in Chinese on the moon phase with different print and image integration were compared--a traditional textbook (TT) used in Taiwanese junior high schools and a…

  14. Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

    PubMed Central

    Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

    2015-01-01

    Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

  15. New Applications of Cardiac Computed Tomography: Dual-Energy, Spectral, and Molecular CT Imaging.

    PubMed

    Danad, Ibrahim; Fayad, Zahi A; Willemink, Martin J; Min, James K

    2015-06-01

    Computed tomography (CT) has evolved into a powerful diagnostic tool, and it is impossible to imagine current clinical practice without CT imaging. Because of its widespread availability, ease of clinical application, superb sensitivity for the detection of coronary artery disease, and noninvasive nature, CT has become a valuable tool within the armamentarium of cardiologists. In the past few years, numerous technological advances in CT have occurred, including dual-energy CT, spectral CT, and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging tool that permits accurate plaque characterization, assessment of myocardial perfusion, and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

  16. Managing incidental pancreatic cystic neoplasms with integrated molecular pathology is a cost-effective strategy

    PubMed Central

    Das, Ananya; Brugge, William; Mishra, Girish; Smith, Dennis M.; Sachdev, Mankanwal; Ellsworth, Eric

    2015-01-01

    Background and study aims: Current guidelines recommend using endoscopic ultrasound (EUS), carcinoembryonic antigen (CEA) testing and cytology to manage incidental pancreatic cystic neoplasms (PCN); however, studies suggest a strategy including integrated molecular pathology (IMP) of cyst fluid may further aid in predicting risk of malignancy. Here, we evaluate several strategies for diagnosing and managing asymptomatic PCN using healthcare economic modeling. Patients and methods: A third-party-payer perspective Markov decision model examined four management strategies in a hypothetical cohort of 1000 asymptomatic patients incidentally found to have a 3 cm solitary pancreatic cystic lesion. Strategy I used cross-sectional imaging, recommended surgery only if symptoms or risk factors emerged. Strategy II considered patients for resection without initial EUS. Strategy III (EUS + CEA + Cytology) referred only those with mucinous cysts (CEA > 192 ng/mL) for resection. Strategy IV implemented IMP; a commercially available panel provided a “Benign,” “Mucinous,” or “Aggressive” classification based on the level of mutational change in cyst fluid. “Benign” and “Mucinous” patients were followed with surveillance; “Aggressive” patients were referred for resection. Quality-adjusted life-years (QALY), relative risk with 95 %CI, Number Needed to Treat (NNT), and incremental cost-effectiveness ratios were calculated. Results: Strategy IV provided the greatest increase in QALY at nearly identical cost to the cheapest approach, Strategy I. Relative risk of malignancy compared to the current standard of care and nearest competing strategy, Strategy III, was 0.18 (95 %CI 0.06 – 0.53) with an NNT of 56 (95 %CI 34 – 120). Conclusions: Use of IMP was the most cost-effective strategy, supporting its routine clinical use. PMID:26528505

  17. Fluorescent X-Ray Computed Tomography towards Molecular Imaging: Proof-of-Concept Experiments

    SciTech Connect

    Yuasa, Tetsuya; Huo, Qingkai; Akatsuka, Takao; Takeda, Tohoru; Hyodo, Kazuyuki; Dilmanian, F. Avraham

    2009-03-10

    By means of fluorescent x-ray computed tomography (FXCT) one can detect and image a distribution of non-radioactive imaging agent, e.g., iodine, in a biomedical subject at a high spatial resolution, so it can be a novel molecular imaging modality. We have been studying an FXCT system using synchrotron radiation for in-vivo imaging brains of small animals such as mouse, or rat. For the purpose, we propose a fast FXCT imaging method based on the novel geometry. In this study, we prove the feasibility of this concept and investigate its imaging properties, including spatial and contrast resolutions and quantitativeness, by imaging an acrylic phantom and a normal mouse brain using a preliminary imaging system with monochromatic synchrotron x rays.

  18. Video-rate molecular imaging in vivo with stimulated Raman scattering.

    PubMed

    Saar, Brian G; Freudiger, Christian W; Reichman, Jay; Stanley, C Michael; Holtom, Gary R; Xie, X Sunney

    2010-12-01

    Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans. PMID:21127249

  19. Synthetic aperture integration (SAI) algorithm for SAR imaging

    DOEpatents

    Chambers, David H; Mast, Jeffrey E; Paglieroni, David W; Beer, N. Reginald

    2013-07-09

    A method and system for detecting the presence of subsurface objects within a medium is provided. In some embodiments, the imaging and detection system operates in a multistatic mode to collect radar return signals generated by an array of transceiver antenna pairs that is positioned across the surface and that travels down the surface. The imaging and detection system pre-processes the return signal to suppress certain undesirable effects. The imaging and detection system then generates synthetic aperture radar images from real aperture radar images generated from the pre-processed return signal. The imaging and detection system then post-processes the synthetic aperture radar images to improve detection of subsurface objects. The imaging and detection system identifies peaks in the energy levels of the post-processed image frame, which indicates the presence of a subsurface object.

  20. Improvement of integral 3D image quality by compensating for lens position errors

    NASA Astrophysics Data System (ADS)

    Okui, Makoto; Arai, Jun; Kobayashi, Masaki; Okano, Fumio

    2004-05-01

    Integral photography (IP) or integral imaging is a way to create natural-looking three-dimensional (3-D) images with full parallax. Integral three-dimensional television (integral 3-D TV) uses a method that electronically presents 3-D images in real time based on this IP method. The key component is a lens array comprising many micro-lenses for shooting and displaying. We have developed a prototype device with about 18,000 lenses using a super-high-definition camera with 2,000 scanning lines. Positional errors of these high-precision lenses as well as the camera's lenses will cause distortions in the elemental image, which directly affect the quality of the 3-D image and the viewing area. We have devised a way to compensate for such geometrical position errors and used it for the integral 3-D TV prototype, resulting in an improvement in both viewing zone and picture quality.

  1. Molecular imaging to target transplanted muscle progenitor cells.

    PubMed

    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

  2. Full-parallax 360 degrees horizontal viewing integral imaging using anamorphic optics

    NASA Astrophysics Data System (ADS)

    Erdenebat, Munkh-Uchral; Baasantseren, Ganbat; Park, Jae-Hyeung; Kim, Nam; Kwon, Ki-Chul; Jang, Young-Hee; Yoo, Kwan-Hee

    2011-03-01

    We propose full-parallax integral imaging display with 360 degree horizontal viewing angle. Two-dimensional (2D) elemental images are projected by a high-speed DMD projector and integrated into three-dimensional (3D) image by a lens array. The anamorphic optic system tailors the horizontal and vertical viewing angles of the integrated 3D images in order to obtain high angular ray density in horizontal direction and large viewing angle in vertical direction. Finally, the mirror screen that rotates in synchronization with the DMD projector presents the integrated 3D images to desired direction accordingly. Full-parallax and 360 degree horizontal viewing angle 3D images with both of monocular and binocular depth cues can be achieved by the proposed method.

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

    PubMed Central

    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.

  4. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    NASA Astrophysics Data System (ADS)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  5. In vivo integrated photoacoustic ophthalmoscopy, optical coherence tomography, and scanning laser ophthalmoscopy for retinal imaging

    NASA Astrophysics Data System (ADS)

    Song, Wei; Zhang, Rui; Zhang, Hao F.; Wei, Qing; Cao, Wenwu

    2012-12-01

    The physiological and pathological properties of retina are closely associated with various optical contrasts. Hence, integrating different ophthalmic imaging technologies is more beneficial in both fundamental investigation and clinical diagnosis of several blinding diseases. Recently, photoacoustic ophthalmoscopy (PAOM) was developed for in vivo retinal imaging in small animals, which demonstrated the capability of imaging retinal vascular networks and retinal pigment epithelium (RPE) at high sensitivity. We combined PAOM with traditional imaging modalities, such as fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and auto-fluorescence scanning laser ophthalmoscopy (AF-SLO), for imaging rats and mice. The multimodal imaging system provided more comprehensive evaluation of the retina based on the complementary imaging contrast mechanisms. The high-quality retinal images show that the integrated ophthalmic imaging system has great potential in the investigation of blinding disorders.

  6. The need for novel informatics tools for integrating and planning research in molecular and cellular cognition.

    PubMed

    Silva, Alcino J; Müller, Klaus-Robert

    2015-09-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning. PMID:26286658

  7. Clinical evaluation of using semantic searching engine for radiological imaging services in RIS-integrated PACS

    NASA Astrophysics Data System (ADS)

    Ling, Tonghui; Zhang, Kai; Yang, Yuanyuan; Hua, Yanqing; Zhang, Jianguo

    2015-03-01

    We had designed a semantic searching engine (SSE) for radiological imaging to search both reports and images in RIS-integrated PACS environment. In this presentation, we present evaluation results of this SSE about how it impacting the radiologists' behaviors in reporting for different kinds of examinations, and how it improving the performance of retrieval and usage of historical images in RIS-integrated PACS.

  8. Heterogeneous photonic integrated circuits and their applications in computing, networking, and imaging

    NASA Astrophysics Data System (ADS)

    Yoo, S. J. Ben

    2014-03-01

    We discuss heterogeneous integrations and their impacts on computing, networking, and imaging applications. We will review photonic integration technologies including silicon, InP, GaAs, SiO2, Si3N4, and magneto-optical materials such as YIG and BIG. We will address new architectures, new capabilities, and performance enhancement brought into computing, networking, and imaging architectures through heterogeneous photonic integration.

  9. Molecular 'OR' and 'AND' logic gates integrated in a single molecule

    NASA Astrophysics Data System (ADS)

    Ami, S.; Hliwa, M.; Joachim, C.