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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.

  2. Integrated Molecular Imaging and Therapy for Breast Cancer

    DTIC Science & Technology

    2008-08-01

    nanoshells [8-9] and nanotubes [10-11] have been shown in the past to be quite applicable for cancer imaging and therapy. Subcellular nanostructures...micro- surgery and cell repair machineries. While nanoshells have been targeted to the surface receptor of cancer cells in the past [4], in this...universally expressed in cells and nanoshells have targeted more breast cancer relevant Her2 surface receptor. We have taken this a step further by showing

  3. Integrated Molecular Imaging and Therapy for Breast Cancer

    DTIC Science & Technology

    2007-08-01

    nanoshells [8-9] and nanotubes [10-11] have been shown in the past to be quite applicable for cancer imaging and therapy. Subcellular nanostructures...micro- surgery and cell repair machineries. While nanoshells have been targeted to the surface receptor of cancer cells in the past [4], in this...universally expressed in cells and nanoshells have targeted more breast cancer relevant Her2 surface receptor. We have taken this a step further by showing

  4. 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

  5. Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging.

    PubMed Central

    Nicholson, C; Tao, L

    1993-01-01

    This paper describes the theory of an integrative optical imaging system and its application to the analysis of the diffusion of 3-, 10-, 40-, and 70-kDa fluorescent dextran molecules in agarose gel and brain extracellular microenvironment. The method uses a precisely defined source of fluorescent molecules pressure ejected from a micropipette, and a detailed theory of the intensity contributions from out-of-focus molecules in a three-dimensional medium to a two-dimensional image. Dextrans tagged with either tetramethylrhodamine or Texas Red were ejected into 0.3% agarose gel or rat cortical slices maintained in a perfused chamber at 34 degrees C and imaged using a compound epifluorescent microscope with a 10 x water-immersion objective. About 20 images were taken at 2-10-s intervals, recorded with a cooled CCD camera, then transferred to a 486 PC for quantitative analysis. The diffusion coefficient in agarose gel, D, and the apparent diffusion coefficient, D*, in brain tissue were determined by fitting an integral expression relating the measured two-dimensional image intensity to the theoretical three-dimensional dextran concentration. The measurements in dilute agarose gel provided a reference value of D and validated the method. Values of the tortuosity, lambda = (D/D*)1/2, for the 3- and 10-kDa dextrans were 1.70 and 1.63, respectively, which were consistent with previous values derived from tetramethylammonium measurements in cortex. Tortuosities for the 40- and 70-kDa dextrans had significantly larger values of 2.16 and 2.25, respectively. This suggests that the extracellular space may have local constrictions that hinder the diffusion of molecules above a critical size that lies in the range of many neurotrophic compounds. Images FIGURE 6 FIGURE 8 PMID:7508761

  6. 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.

  7. 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

  8. Molecular imaging in endoscopy

    PubMed Central

    Hoetker, Michael S

    2013-01-01

    Molecular imaging focuses on the molecular signature of cells rather than morphological changes in the tissue. The need for this novel type of imaging arises from the often difficult detection and characterization especially of small and/or premalignant lesions. Molecular imaging specifically visualizes biological properties of a lesion and might thereby be able to close diagnostic gaps, e.g. when differentiating hyperplastic from neoplastic polyps or detecting the margins of intraepithelial neoplastic spread. Additionally, not only the detection and discrimination of lesions could be improved: based on the molecular features identified using molecular imaging, therapy regimens could be adjusted on the day of diagnosis to allow for personalized medicine and optimized care for each individual patient. PMID:24917945

  9. 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.

  10. Molecular Imaging of Ovarian Cancer

    PubMed Central

    Sharma, Sai Kiran; Nemieboka, Brandon; Sala, Evis; Lewis, Jason S.; Zeglis, Brian M.

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer. PMID:27127223

  11. 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

  12. Molecular imaging for personalized cancer care.

    PubMed

    Kircher, Moritz F; Hricak, Hedvig; Larson, Steven M

    2012-04-01

    Molecular imaging is rapidly gaining recognition as a tool with the capacity to improve every facet of cancer care. Molecular imaging in oncology can be defined as in vivo characterization and measurement of the key biomolecules and molecularly based events that are fundamental to the malignant state. This article outlines the basic principles of molecular imaging as applied in oncology with both established and emerging techniques. It provides examples of the advantages that current molecular imaging techniques offer for improving clinical cancer care as well as drug development. It also discusses the importance of molecular imaging for the emerging field of theranostics and offers a vision of how molecular imaging may one day be integrated with other diagnostic techniques to dramatically increase the efficiency and effectiveness of cancer care.

  13. 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.

  14. Integrated Dual Imaging Detector

    NASA Technical Reports Server (NTRS)

    Rust, David M.

    1999-01-01

    A new type of image detector was designed to simultaneously analyze the polarization of light at all picture elements in a scene. The integrated Dual Imaging detector (IDID) consists of a lenslet array and a polarizing beamsplitter bonded to a commercial charge coupled device (CCD). The IDID simplifies the design and operation of solar vector magnetographs and the imaging polarimeters and spectroscopic imagers used, for example, in atmosphere and solar research. When used in a solar telescope, the vector magnetic fields on the solar surface. Other applications include environmental monitoring, robot vision, and medical diagnoses (through the eye). Innovations in the IDID include (1) two interleaved imaging arrays (one for each polarization plane); (2) large dynamic range (well depth of 10(exp 5) electrons per pixel); (3) simultaneous readout and display of both images; and (4) laptop computer signal processing to produce polarization maps in field situations.

  15. Nanoparticles for molecular imaging.

    PubMed

    Sheng, Yang; Liao, Lun De; Thakor, Nitish V; Tan, Mei Chee

    2014-10-01

    Imaging techniques have been instrumental in the visualization of fundamental biological processes, identification and diagnosis of diseased states and the development of structure-function relationships at the cellular, tissue and anatomical levels. Together with the advancements made in imaging techniques, complementary chemical compounds, also known as imaging probes or contrast agents, are developed to improve the visibility of the image by enhancing sensitivity, and for the identification and quantitation of specific molecular species or structures. Extensive studies have been conducted to explore the use of inorganic nanoparticles which exhibit magnetic and optical properties unique to the nano regime so as to enhance the signals sensitivity for magnetic resonance and fluorescent imaging. These physical properties are tailored by controlling the size, shape and surface properties of nanoparticles. In addition, surface modification of nanoparticles is often required to improve its stability, compatibility and functionality. Surfactants, surface-active agents, have been used to engineer the surface characteristics of nanoparticles to improved particle stability and functionality. Surfactants enhance nanoparticle stability through the reduction of surface energy, and by acting as a barrier to agglomeration through either steric hindrance or repulsive electrostatic forces. Coupling of nanoparticles with biomolecules such as antibodies or tumor targeting peptides are enabled by the presence of functional groups (e.g., carboxyl or amine groups) on surfactants. This paper provides an overview of the chemistry underlying the synthesis and surface modification of nanomaterials together with a discussion on how the physical properties (e.g., magnetic, absorption and luminescent) can be controlled. The applications of these nanoparticles for magnetic resonance, fluorescent and photoacoustic imaging techniques that do not rely on ionizing radiation are also covered in

  16. Molecular imaging applications for immunology.

    PubMed

    Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam

    2004-05-01

    The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.

  17. Molecular imaging in atherosclerosis.

    PubMed

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

    2010-12-01

    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

  18. Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

    PubMed Central

    Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

    2017-01-01

    Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies. PMID:28358042

  19. Integration of High-Volume Molecular and Imaging Data for Composite Biomarker Discovery in the Study of Melanoma

    PubMed Central

    Chatziioannou, Aristotelis

    2014-01-01

    In this work the effects of simple imputations are studied, regarding the integration of multimodal data originating from different patients. Two separate datasets of cutaneous melanoma are used, an image analysis (dermoscopy) dataset together with a transcriptomic one, specifically DNA microarrays. Each modality is related to a different set of patients, and four imputation methods are employed to the formation of a unified, integrative dataset. The application of backward selection together with ensemble classifiers (random forests), followed by principal components analysis and linear discriminant analysis, illustrates the implication of the imputations on feature selection and dimensionality reduction methods. The results suggest that the expansion of the feature space through the data integration, achieved by the exploitation of imputation schemes in general, aids the classification task, imparting stability as regards the derivation of putative classifiers. In particular, although the biased imputation methods increase significantly the predictive performance and the class discrimination of the datasets, they still contribute to the study of prominent features and their relations. The fusion of separate datasets, which provide a multimodal description of the same pathology, represents an innovative, promising avenue, enhancing robust composite biomarker derivation and promoting the interpretation of the biomedical problem studied. PMID:24527435

  20. Molecular imaging with engineered physiology

    PubMed Central

    Desai, Mitul; Slusarczyk, Adrian L.; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-01-01

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms. PMID:27910951

  1. Molecular imaging with engineered physiology.

    PubMed

    Desai, Mitul; Slusarczyk, Adrian L; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-12-02

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.

  2. Multi-modality molecular imaging for gastric cancer research

    NASA Astrophysics Data System (ADS)

    Liang, Jimin; Chen, Xueli; Liu, Junting; Hu, Hao; Qu, Xiaochao; Wang, Fu; Nie, Yongzhan

    2011-12-01

    Because of the ability of integrating the strengths of different modalities and providing fully integrated information, multi-modality molecular imaging techniques provide an excellent solution to detecting and diagnosing earlier cancer, which remains difficult to achieve by using the existing techniques. In this paper, we present an overview of our research efforts on the development of the optical imaging-centric multi-modality molecular imaging platform, including the development of the imaging system, reconstruction algorithms and preclinical biomedical applications. Primary biomedical results show that the developed optical imaging-centric multi-modality molecular imaging platform may provide great potential in the preclinical biomedical applications and future clinical translation.

  3. Advances in multimodal molecular imaging.

    PubMed

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

    2017-03-01

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

  4. 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

  5. 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.

  6. TU-CD-BRB-02: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Identification of Molecular Phenotypes by Integrating Radiomics and Genomics

    SciTech Connect

    Grossmann, P; Velazquez, E Rios; Parmar, C; Aerts, H; El-Hachem, N; Leijenaar, R; Haibe-Kains, B; Lambin, P

    2015-06-15

    Purpose: To uncover the mechanistic connections between radiomic features, molecular pathways, and clinical outcomes, to develop radiomic based predictors of pathway activation states in individual patients, and to assess whether combining radiomic with clinical and genomic data improves prognostication. Methods: We analyzed two independent lung cancer cohorts totaling 351 patients, for whom diagnostic computed tomography (CT) scans, gene-expression profiles, and clinical outcomes were available. The tumor phenotype was characterized based on 636 radiomic features describing tumor intensity, texture, shape and size. We performed an integrative analysis by developing and independently validating association modules of coherently expressed radiomic features and molecular pathways. These modules were statistically tested for significant associations to overall survival (OS), TNM stage, and pathologic histology. Results: We identified thirteen radiomic-pathway association modules (p < 0.05), the most prominent of which were associated with the immune system, p53 pathway, and other pathways involved in cell cycle regulation. Eleven modules were significantly associated with clinical outcomes (p < 0.05). Strong predictive power for pathway activation states in individual patients was observed using radiomics; the strongest per module predictions ranged from an intra-tumor heterogeneity feature predicting RNA III polymerase transcription (AUC 0.62, p = 0.03), to a tumor intensity dispersion feature predicting pyruvate metabolism and citric acid TCA cycle (AUC 0.72, p < 10−{sup 6}). Stepwise combinations of radiomic data with clinical outcomes and gene expression profiles resulted in consistent increases of prognostic power to predict OS (concordance index max = 0.73, p < 10−{sup 9}). Conclusion: This study demonstrates that radiomic approaches permit a non-invasive assessment of molecular and clinical characteristics of tumors, and therefore have the unprecedented

  7. 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

  8. Molecular imaging in cancer treatment

    PubMed Central

    Michalski, Mark H.

    2010-01-01

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. PMID:20661557

  9. Molecular Imaging of the Kidneys

    PubMed Central

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

    2010-01-01

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

  10. Molecular imaging in the eye.

    PubMed

    Eter, Nicole

    2010-11-01

    Molecular imaging plays an increasingly powerful role in elucidating pathophysiological pathways, in advancing drug discovery and in deciphering developmental processes. Multiple modalities, including optical imaging, ultrasound, nuclear imaging, computed tomography and various techniques of MRI are now being used to obtain fundamental new insights at the cellular and molecular level, both in basic research, using animal models and in clinical studies. In permitting unique optical access, the eye is particularly well suited for molecular imaging, for example, transgenic mice in which the fractalkine receptor is rendered intrinsically fluorescent to allow for in vivo monitoring of myeloid immune cells within the retina and choroid by scanning laser ophthalmoscopy (SLO). Retinal cell apoptosis can be assessed by intravitreal injection of fluorescent-labelled annexin 5 in vivo using a similar SLO technique. Intravital microscopy also allows visualisation of CD11c-positive dendritic cells in transgenic mice expressing yellow-fluorescent protein in these immune cells. Adoptive transfer of fluorescent-labelled transgenic T-cells enables visualisation of infiltration by specific T-cells into various eye compartments. On the other hand, functional imaging can be provided by new MR methodologies: deuterium MRI and diffusion MRI analysis techniques permit dynamic studies of water movement in animal eyes. MRI also enables pharmacokinetic studies on ocular drug delivery and detects biomarkers for treatment efficacy in retinopathies. Undoubtedly, these and further molecular imaging techniques currently being developed will have a fundamental impact on experimental and clinical ophthalmology and thus on our understanding of eye disease and development of therapy in general.

  11. 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

  12. 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

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

    PubMed

    Yang, Jack Y; Yang, Mary Qu; Arabnia, Hamid R; Deng, Youping

    2008-09-16

    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.

  14. Molecular imaging with theranostic nanoparticles.

    PubMed

    Jokerst, Jesse V; Gambhir, Sanjiv S

    2011-10-18

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

  15. Clinical applications in molecular imaging.

    PubMed

    Heneweer, Carola; Grimm, Jan

    2011-02-01

    Molecular imaging is aimed at the noninvasive in vivo characterization and measurement of processes at a cellular and molecular level with clinical imaging methods. Contrast agents are constructed to target markers that are specific either for certain diseases or for functional states of specialized tissues. Efforts are currently focused mainly on processes involved in angiogenesis, inflammation, and apoptosis. Cell tracking is performed for diagnostic purposes as well as for monitoring of novel cell therapies. Visualization of these processes would provide more precise information about disease expansion as well as treatment response, and could lead to a more individualized therapy for patients. Many attempts have shown promising results in preclinical studies; however, translation into the clinic remains a challenge. This applies especially to paediatrics because of more stringent safety concerns and the low prevalence of individual diseases. The most promising modalities for clinical translation are nuclear medicine methods (positron emission tomography [PET] and single photon emission CT [SPECT]) due to their high sensitivity, which allows concentrations below biological activity. However, special dose consideration is required for any application of ionizing radiation especially in children. While very little has been published on molecular imaging in a paediatric patient population beyond fluorodeoxyglucose (FDG)-PET and metaiodobenzylguanidine (MIBG) tracers, this review will attempt to discuss approaches that we believe have promise for paediatric imaging. These will include agents that already reached clinical trials as well as preclinical developments with high potential for clinical application.

  16. 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

  17. Imaging by integrating stitched spectrograms.

    PubMed

    Teale, Carson; Adams, Dan; Murnane, Margaret; Kapteyn, Henry; Kane, Daniel J

    2013-03-25

    A new diffractive imaging technique called Imaging By Integrating Stitched Spectrograms (IBISS) is presented. Both the data collection and phase retrieval algorithm used in IBISS are direct extensions of frequency resolved optical gating to higher dimensions. Data collection involves capturing an array of diffraction patterns generated by scanning a sample across a coherent beam of light. Phase retrieval is performed using the Principal Components Generalized Projections Algorithm (PCGPA) by reducing the four dimensional data set of images to two remapped two-dimensional sets. The technique is successfully demonstrated using a Helium Neon laser to image a 350μm wide sample with 12μm resolution.

  18. 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

  19. 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

  20. Integration of retinal image sequences

    NASA Astrophysics Data System (ADS)

    Ballerini, Lucia

    1998-10-01

    In this paper a method for noise reduction in ocular fundus image sequences is described. The eye is the only part of the human body where the capillary network can be observed along with the arterial and venous circulation using a non invasive technique. The study of the retinal vessels is very important both for the study of the local pathology (retinal disease) and for the large amount of information it offers on systematic haemodynamics, such as hypertension, arteriosclerosis, and diabetes. In this paper a method for image integration of ocular fundus image sequences is described. The procedure can be divided in two step: registration and fusion. First we describe an automatic alignment algorithm for registration of ocular fundus images. In order to enhance vessel structures, we used a spatially oriented bank of filters designed to match the properties of the objects of interest. To evaluate interframe misalignment we adopted a fast cross-correlation algorithm. The performances of the alignment method have been estimated by simulating shifts between image pairs and by using a cross-validation approach. Then we propose a temporal integration technique of image sequences so as to compute enhanced pictures of the overall capillary network. Image registration is combined with image enhancement by fusing subsequent frames of a same region. To evaluate the attainable results, the signal-to-noise ratio was estimated before and after integration. Experimental results on synthetic images of vessel-like structures with different kind of Gaussian additive noise as well as on real fundus images are reported.

  1. Integrating image processing in PACS.

    PubMed

    Faggioni, Lorenzo; Neri, Emanuele; Cerri, Francesca; Turini, Francesca; Bartolozzi, Carlo

    2011-05-01

    Integration of RIS and PACS services into a single solution has become a widespread reality in daily radiological practice, allowing substantial acceleration of workflow with greater ease of work compared with older generation film-based radiological activity. In particular, the fast and spectacular recent evolution of digital radiology (with special reference to cross-sectional imaging modalities, such as CT and MRI) has been paralleled by the development of integrated RIS--PACS systems with advanced image processing tools (either two- and/or three-dimensional) that were an exclusive task of costly dedicated workstations until a few years ago. This new scenario is likely to further improve productivity in the radiology department with reduction of the time needed for image interpretation and reporting, as well as to cut costs for the purchase of dedicated standalone image processing workstations. In this paper, a general description of typical integrated RIS--PACS architecture with image processing capabilities will be provided, and the main available image processing tools will be illustrated.

  2. 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

  3. 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

  4. 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

  5. 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)

  6. 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.

  7. Techniques for Molecular Imaging Probe Design

    PubMed Central

    Reynolds, Fred; Kelly, Kimberly A.

    2011-01-01

    Molecular imaging allows clinicians to visualize disease specific molecules, thereby providing relevant information in the diagnosis and treatment of patients. With advances in genomics and proteomics and underlying mechanisms of disease pathology, the number of targets identified has significantly outpaced the number of developed molecular imaging probes. There has been a concerted effort to bridge this gap with multidisciplinary efforts in chemistry, proteomics, physics, material science, and biology; all essential to progress in molecular imaging probe development. In this review, we will discuss target selection, screening techniques and probe optimization with the aim of developing clinically relevant molecularly targeted imaging agents. PMID:22201532

  8. Techniques for molecular imaging probe design.

    PubMed

    Reynolds, Fred; Kelly, Kimberly A

    2011-12-01

    Molecular imaging allows clinicians to visualize disease-specific molecules, thereby providing relevant information in the diagnosis and treatment of patients. With advances in genomics and proteomics and underlying mechanisms of disease pathology, the number of targets identified has significantly outpaced the number of developed molecular imaging probes. There has been a concerted effort to bridge this gap with multidisciplinary efforts in chemistry, proteomics, physics, material science, and biology--all essential to progress in molecular imaging probe development. In this review, we discuss target selection, screening techniques, and probe optimization with the aim of developing clinically relevant molecularly targeted imaging agents.

  9. 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

  10. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    PubMed Central

    Lee, Soo Jin

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced. PMID:26357491

  11. 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.

  12. 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

  13. Integrated imaging of cardiac anatomy, physiology, and viability.

    PubMed

    Arrighi, James A

    2009-03-01

    Technologic developments in imaging will have a significant impact on cardiac imaging over the next decade. These advances will permit more detailed assessment of cardiac anatomy, complex assessment of cardiac physiology, and integration of anatomic and physiologic data. The distinction between anatomic and physiologic imaging is important. For assessing patients with known or suspected coronary artery disease, physiologic and anatomic imaging data are complementary. The strength of anatomic imaging rests in its ability to detect the presence of disease, whereas physiologic imaging techniques assess the impact of disease, such as whether a coronary atherosclerotic lesion limits myocardial blood flow. Research indicates that physiologic data are more prognostically important than anatomic data, but both may be important in patient management decisions. Integrated cardiac imaging is an evolving field, with many potential indications. These include assessment of coronary stenosis, myocardial viability, anatomic and physiologic characterization of atherosclerotic plaque, and advanced molecular imaging.

  14. In vivo Noninvasive Small Animal Molecular Imaging

    PubMed Central

    Youn, Hyewon; Hong, Kee-Jong

    2012-01-01

    The remarkable efforts that are made on molecular imaging technologies demonstrate its potential importance and range of applications. The generation of disease-specific animal models, and the developments of target-specific probes and genetically encoded reporters are another important component. Continued improvements in the instrumentation, the identification of novel targets and genes, and the availability of improved imaging probes should be made. Multimodal imaging probes should provide easier transitions between laboratory studies, including small animal studies and clinical applications. Here, we reviewed basic strategies of noninvasive in vivo imaging methods in small animals to introducing the concept of molecular imaging. PMID:24159487

  15. Advances in Molecular Imaging with Ultrasound

    PubMed Central

    Gessner, Ryan; Dayton, Paul A.

    2010-01-01

    Ultrasound imaging has long demonstrated utility in the study and measurement of anatomic features and noninvasive observation of blood flow. Within the last decade, advances in molecular biology and contrast agents have allowed researchers to use ultrasound to detect changes in the expression of molecular markers on the vascular endothelium and other intravascular targets. This new technology, referred to as ultrasonic molecular imaging, is still in its infancy. However, in preclinical studies, ultrasonic molecular imaging has shown promise in assessing angiogenesis, inflammation, and thrombus. In this review, we discuss recent advances in microbubble-type contrast agent development, ultrasound technology, and signal processing strategies that have the potential to substantially improve the capabilities and utility of ultrasonic molecular imaging. PMID:20487678

  16. 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

  17. PET-based molecular imaging in neuroscience.

    PubMed

    Jacobs, A H; Li, H; Winkeler, A; Hilker, R; Knoess, C; Rüger, A; Galldiks, N; Schaller, B; Sobesky, J; Kracht, L; Monfared, P; Klein, M; Vollmar, S; Bauer, B; Wagner, R; Graf, R; Wienhard, K; Herholz, K; Heiss, W D

    2003-07-01

    Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

  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. Ultrasound molecular imaging: Moving toward clinical translation.

    PubMed

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

    2015-09-01

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

  20. Acoustic and photoacoustic molecular imaging of cancer.

    PubMed

    Wilson, Katheryne E; Wang, Tzu Yin; Willmann, Jürgen K

    2013-11-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed.

  1. Enhanced integral imaging system using image floating technique

    NASA Astrophysics Data System (ADS)

    Min, Sung-Wook; Kim, Joohwan; Lee, Byoungho

    2005-09-01

    Enhanced integral imaging system based on the image floating method is proposed. The integral imaging is one of the most promising methods among the autostereoscopic displays and the integrated image has the volumetric characteristics unlike the other stereoscopic images. The image floating is a common 3D display technique, which uses a big convex lens or a concave mirror to exhibit the image of a real object to the observer. The image floating method can be used to emphasize the viewing characteristics of the volumetric image and the noise image which is located on the fixed plane can be eliminated by the floating lens through the control of the focal length. In this paper, the solution of the seam noise and the image flipping of the integral imaging system is proposed using the image floating method. Moreover, the advanced techniques of the integral imaging system can be directly applied to the proposed system. The proposed system can be successfully applied to many 3D applications such as 3D television.

  2. Molecular Imaging in Breast Cancer – Potential Future Aspects

    PubMed Central

    Pinker, Katja; Bogner, Wolfgang; Gruber, Stephan; Brader, Peter; Trattnig, Siegfried; Karanikas, Georgios; Helbich, Thomas H.

    2011-01-01

    Summary Molecular imaging aims to visualize and quantify biological, physiological, and pathological processes at cellular and molecular levels. Recently, molecular imaging has been introduced into breast cancer imaging. In this review, we will present a survey of the molecular imaging techniques that are either clinically available or are being introduced into clinical imaging. We will discuss nuclear imaging and multiparametric magnetic resonance imaging as well as the combined application of molecular imaging in the assessment of breast lesions. In addition, we will briefly discuss other evolving molecular imaging techniques, such as phosphorus magnetic resonance spectroscopic imaging and sodium imaging. PMID:21673821

  3. 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

  4. 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.

  5. Molecular Slater Integrals for Electronic Energy Calculations

    DTIC Science & Technology

    2010-10-15

    Facultad de Ciencias . Departamento de Quı́mica Fı́sica Aplicada. C-XIV. Abstract The algorithms for computing molecular integrals with Slater functions...and propulsion sciences research programs. This extension requires a thorough revision on the performance of the algorithms currently available and

  6. Fundamental considerations for multiwavelength photoacoustic molecular imaging

    NASA Astrophysics Data System (ADS)

    Zemp, Roger J.; Li, Li; Wang, Lihong V.

    2006-02-01

    Photoacoustic technology offers great promise for molecular imaging in vivo since it offers significant penetration, and optical contrast with ultrasonic spatial resolution. In this article we examine fundamental technical issues impacting capabilities of photoacoustic tomography for molecular imaging. First we examine how reconstructed photoacoustic tomography images are related to true absorber distributions by studying the modulation transfer function of a circular scanning tomographic system employing a modified filtered backprojection algorithm. We then study factors influencing quantitative estimation by developing a forward model of photoacoustic signal generation, and show conditions for which the system of equations can be inverted. Errors in the estimated optical fluence are shown to be a source of bias in estimates of molecular agent concentration. Finally we discuss noise propagation through the matrix inversion procedure and discuss implications for molecular imaging sensitivity and system design.

  7. 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

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

    PubMed Central

    Tian, Mei; Zhang, Hong

    2014-01-01

    Spinal cord injury (SCI) is a serious disease of the center nervous system (CNS). It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging (i.e., bioluminescence imaging (BLI)) gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI. PMID:24701583

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Quantitative molecular thermochemistry based on path integrals.

    PubMed

    Glaesemann, Kurt R; Fried, Laurence E

    2005-07-15

    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 for going beyond the harmonic analysis and to calculate the vibrational and rotational contributions to ab initio energies. This is an application and an extension of a method previously developed in our group [J. Chem. Phys. 118, 1596 (2003)].

  14. Molecular and functional imaging of internet addiction.

    PubMed

    Zhu, Yunqi; Zhang, Hong; Tian, Mei

    2015-01-01

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

  15. Bead-Fourier path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ivanov, Sergei D.; Lyubartsev, Alexander P.; Laaksonen, Aatto

    2003-06-01

    Molecular dynamics formulation of Bead-Fourier path integral method for simulation of quantum systems at finite temperatures is presented. Within this scheme, both the bead coordinates and Fourier coefficients, defining the path representing the quantum particle, are treated as generalized coordinates with corresponding generalized momenta and masses. Introduction of the Fourier harmonics together with the center-of-mass thermostating scheme is shown to remove the ergodicity problem, known to pose serious difficulties in standard path integral molecular dynamics simulations. The method is tested for quantum harmonic oscillator and hydrogen atom (Coulombic potential). The simulation results are compared with the exact analytical solutions available for both these systems. Convergence of the results with respect to the number of beads and Fourier harmonics is analyzed. It was shown that addition of a few Fourier harmonics already improves the simulation results substantially, even for a relatively small number of beads. The proposed Bead-Fourier path integral molecular dynamics is a reliable and efficient alternative to simulations of quantum systems.

  16. Molecular imaging of Alzheimer disease pathology.

    PubMed

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

  17. Integral volumetric imaging using decentered elemental lenses.

    PubMed

    Sawada, Shimpei; Kakeya, Hideki

    2012-11-05

    This paper proposes a high resolution integral imaging system using a lens array composed of non-uniform decentered elemental lenses. One of the problems of integral imaging is the trade-off relationship between the resolution and the number of views. When the number of views is small, motion parallax becomes strongly discrete to maintain the viewing angle. In order to overcome this trade-off, the proposed method uses the elemental lenses whose size is smaller than that of the elemental images. To keep the images generated by the elemental lenses at constant depth, the lens array is designed so that the optical centers of elemental lenses may be located in the centers of elemental images, not in the centers of elemental lenses. To compensate optical distortion, new image rendering algorithm is developed so that undistorted 3D image may be presented with a non-uniform lens array. The proposed design of lens array can be applied to integral volumetric imaging, where display panels are layered to show volumetric images in the scheme of integral imaging.

  18. Luminescence-based Imaging Approaches in the Field of Interventional Molecular Imaging.

    PubMed

    van Leeuwen, Fijs W B; Hardwick, James C H; van Erkel, Arian R

    2015-07-01

    Luminescence imaging-based guidance technologies are increasingly gaining interest within surgical and radiologic disciplines. Their promise to help visualize molecular features of disease in real time and with microscopic detail is considered desirable. Integrating luminescence imaging with three-dimensional radiologic- and/or nuclear medicine-based preinterventional imaging may overcome limitations such as the limited tissue penetration of luminescence signals. At the same time, the beneficial features of luminescence imaging may be used to complement the routinely used radiologic- and nuclear medicine-based modalities. To fully exploit this integrated concept, and to relate the largely experimental luminesce-based guidance approaches into perspective with routine imaging approaches, it is essential to understand the advantages and limitations of this relatively new modality. By providing an overview of the available luminescence technologies and the various clinically evaluated exogenous luminescent tracers (fluorescent, hybrid, and theranostic tracers), this review attempts to place luminescence-based interventional molecular imaging technologies into perspective to the available radiologic- and/or nuclear medicine-based imaging technologies. At the same time, the transition from anatomic to physiologic and even molecular interventional luminescence imaging is illustrated.

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

    PubMed Central

    Khondee, Supang; Wang, Thomas D.

    2014-01-01

    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

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

    PubMed

    Sallam, Karim; Wu, Joseph C

    2010-01-01

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

  1. Molecular imaging agents: impact on diagnosis and therapeutics in oncology

    PubMed Central

    Seaman, Marc E.; Contino, Gianmarco; Bardeesy, Nabeel; Kelly, Kimberly A.

    2011-01-01

    Imaging has become a crucial tool in oncology throughout the course of disease detection and management and is an integral part of clinical trials. Anatomic and functional imaging led the way, providing valuable information used in the diagnosis of disease, including data regarding the size and location of the tumor and on physiologic processes such as blood flow and perfusion. As understanding of cancer pathogenesis has advanced through the identification of genetic, biochemical, and cellular alterations in evolving tumors, emphasis has been made on developing methods to detect and serially monitor such alterations. This class of approaches is referred to as molecular imaging. Molecular imaging offers the potential for increasingly sensitive and specific visualization and quantification of biological processes at the cellular and molecular level. These approaches have become established as essential tools for cancer research, early cancer detection and staging and monitoring and predicting response to targeted therapies. Here, we will discuss recent advances in the development of molecular imaging agents and their implementation in basic cancer research as well as in more rationalized approaches to cancer care. PMID:20633310

  2. 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.

  3. Integrating evolutionary and molecular genetics of aging.

    PubMed

    Flatt, Thomas; Schmidt, Paul S

    2009-10-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

  4. 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

  5. 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

  6. 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.

  7. Integrating Advanced Molecular Technologies into Public Health.

    PubMed

    Gwinn, Marta; MacCannell, Duncan R; Khabbaz, Rima F

    2017-03-01

    Advances in laboratory and information technologies are transforming public health microbiology. High-throughput genome sequencing and bioinformatics are enhancing our ability to investigate and control outbreaks, detect emerging infectious diseases, develop vaccines, and combat antimicrobial resistance, all with increased accuracy, timeliness, and efficiency. The Advanced Molecular Detection (AMD) initiative has allowed the Centers for Disease Control and Prevention (CDC) to provide leadership and coordination in integrating new technologies into routine practice throughout the U.S. public health laboratory system. Collaboration and partnerships are the key to navigating this transition and to leveraging the next generation of methods and tools most effectively for public health.

  8. Molecular Imaging in Nanotechnology and Theranostics.

    PubMed

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

    2017-03-27

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

  9. 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

  10. 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.

  11. Molecular histopathology by nonlinear interferometric vibrational imaging

    NASA Astrophysics Data System (ADS)

    Boppart, Stephen A.

    2011-07-01

    A rapid label-free approach for molecular histopathology is presented and reviewed. Broadband vibrational spectra are generated by nonlinear interferometric vibrational imaging (NIVI), a coherent anti-Stokes Raman scattering (CARS)- based technique that uses interferometry and signal processing approaches to acquire Raman-like profiles with suppression of the non-resonant background. This allows for the generation of images that provide contrast based on quantitative chemical composition with high spatial and spectral resolution. Algorithms are demonstrated for reducing the diagnostic spectral information into color-coded composite images for the rapid identification of chemical constituents in skin, as well as differentiating normal from abnormal tissue in a pre-clinical tumor model for human breast cancer. This technology and methodology could result in an alternative method to the traditional histological staining and subjective interpretation procedure currently used in the diagnosis of disease, and has the potential for future in vivo molecular histopathology.

  12. 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.

  13. [Redox Molecular Imaging Using ReMI].

    PubMed

    Hyodo, Fuminori; Ito, Shinji; Utsumi, Hideo

    2015-01-01

    Tissue redox status is one of the most important parameters to maintain homeostasis in the living body. Numerous redox reactions are involved in metabolic processes, such as energy production in the mitochondrial electron transfer system. A variety of intracellular molecules such as reactive oxygen species, glutathione, thioredoxins, NADPH, flavins, and ascorbic acid may contribute to the overall redox status in tissues. Breakdown of redox balance may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore imaging of tissue redox status and monitoring antioxidant levels in living organisms can be useful in the diagnosis of disease states and assessment of treatment response. In vivo redox molecular imaging technology such as electron spin resonance imaging (ESRI), magnetic resonance imaging (MRI), and dynamic nuclear polarization (DNP)-MRI (redox molecular imaging; ReMI) is emerging as a viable redox status imaging modality. This review focuses on the application of magnetic resonance technologies using MRI or DNP-MRI and redox-sensitive contrast agents.

  14. 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

  15. Imaging molecular geometry with electron momentum spectroscopy.

    PubMed

    Wang, Enliang; Shan, Xu; Tian, Qiguo; Yang, Jing; Gong, Maomao; Tang, Yaguo; Niu, Shanshan; Chen, Xiangjun

    2016-12-22

    Electron momentum spectroscopy is a unique tool for imaging orbital-specific electron density of molecule in momentum space. However, the molecular geometry information is usually veiled due to the single-centered character of momentum space wavefunction of molecular orbital (MO). Here we demonstrate the retrieval of interatomic distances from the multicenter interference effect revealed in the ratios of electron momentum profiles between two MOs with symmetric and anti-symmetric characters. A very sensitive dependence of the oscillation period on interatomic distance is observed, which is used to determine F-F distance in CF4 and O-O distance in CO2 with sub-Ångström precision. Thus, using one spectrometer, and in one measurement, the electron density distributions of MOs and the molecular geometry information can be obtained simultaneously. Our approach provides a new robust tool for imaging molecules with high precision and has potential to apply to ultrafast imaging of molecular dynamics if combined with ultrashort electron pulses in the future.

  16. Imaging molecular geometry with electron momentum spectroscopy

    PubMed Central

    Wang, Enliang; Shan, Xu; Tian, Qiguo; Yang, Jing; Gong, Maomao; Tang, Yaguo; Niu, Shanshan; Chen, Xiangjun

    2016-01-01

    Electron momentum spectroscopy is a unique tool for imaging orbital-specific electron density of molecule in momentum space. However, the molecular geometry information is usually veiled due to the single-centered character of momentum space wavefunction of molecular orbital (MO). Here we demonstrate the retrieval of interatomic distances from the multicenter interference effect revealed in the ratios of electron momentum profiles between two MOs with symmetric and anti-symmetric characters. A very sensitive dependence of the oscillation period on interatomic distance is observed, which is used to determine F-F distance in CF4 and O-O distance in CO2 with sub-Ångström precision. Thus, using one spectrometer, and in one measurement, the electron density distributions of MOs and the molecular geometry information can be obtained simultaneously. Our approach provides a new robust tool for imaging molecules with high precision and has potential to apply to ultrafast imaging of molecular dynamics if combined with ultrashort electron pulses in the future. PMID:28004794

  17. Imaging molecular geometry with electron momentum spectroscopy

    NASA Astrophysics Data System (ADS)

    Wang, Enliang; Shan, Xu; Tian, Qiguo; Yang, Jing; Gong, Maomao; Tang, Yaguo; Niu, Shanshan; Chen, Xiangjun

    2016-12-01

    Electron momentum spectroscopy is a unique tool for imaging orbital-specific electron density of molecule in momentum space. However, the molecular geometry information is usually veiled due to the single-centered character of momentum space wavefunction of molecular orbital (MO). Here we demonstrate the retrieval of interatomic distances from the multicenter interference effect revealed in the ratios of electron momentum profiles between two MOs with symmetric and anti-symmetric characters. A very sensitive dependence of the oscillation period on interatomic distance is observed, which is used to determine F-F distance in CF4 and O-O distance in CO2 with sub-Ångström precision. Thus, using one spectrometer, and in one measurement, the electron density distributions of MOs and the molecular geometry information can be obtained simultaneously. Our approach provides a new robust tool for imaging molecules with high precision and has potential to apply to ultrafast imaging of molecular dynamics if combined with ultrashort electron pulses in the future.

  18. Analysis on enhanced depth of field for integral imaging microscope.

    PubMed

    Lim, Young-Tae; Park, Jae-Hyeung; Kwon, Ki-Chul; Kim, Nam

    2012-10-08

    Depth of field of the integral imaging microscope is studied. In the integral imaging microscope, 3-D information is encoded as a form of elemental images Distance between intermediate plane and object point decides the number of elemental image and depth of field of integral imaging microscope. From the analysis, it is found that depth of field of the reconstructed depth plane image by computational integral imaging reconstruction is longer than depth of field of optical microscope. From analyzed relationship, experiment using integral imaging microscopy and conventional microscopy is also performed to confirm enhanced depth of field of integral imaging microscopy.

  19. In vivo molecular contrast OCT imaging of methylene blue.

    PubMed

    Kim, Wihan; Applegate, Brian E

    2015-04-01

    An 830-nm spectral-domain optical coherence tomography (OCT) system with an integrated 663-nm diode pump laser has been developed to enable molecular contrast OCT imaging of methylene blue (MB), a common vital dye used clinically. The introduction of the 663-nm diode laser, which acts as the pump in this implementation of pump-probe OCT (PPOCT), represents a minor modification to an otherwise typical OCT system. A newly developed background subtraction technique completely removes all background from intensity noise at the pump modulation frequency, simplifying the interpretation of PPOCT images. These developments have enabled the first in vivo imaging of MB with PPOCT. Volumetric images of a zebrafish, stained by submersion in a 0.01% (w/v) solution of MB for 6 h, show accumulation of MB in the mesonephros, the primordial filtration organ.

  20. Molecular imaging to biomarker development in neuroscience.

    PubMed

    Frost, J James

    2008-11-01

    CNS drug candidates fail approval in over 90% of the cases due to poor targeting, lack of efficacy, and/or unacceptable side effects. In vivo imaging offers a pathway to derisk drug molecules at each stage of development, but more research and development is needed to fully realize this potential. The greatest activity is in the use of target biomarkers, but those for disease mechanism, efficacy, and toxicological effects are under study and urgently needed. Many of the biomarker tracers can later be developed as new diagnostic imaging agents and then used to guide individual molecular therapy. Realization of this goal will require ongoing collaborative research and development among universities, pharmaceutical companies, biotechnology, the contract research organization (CRO) industry, diagnostic companies, and producers and distributors of radiopharmaceuticals. During the past decade there has been a progressive merger of the interests of the pharmaceutical industry and academia in the area of molecular biomarker imaging in human brain disease. Historically, academia has been more focused on disease mechanisms, etiology, diagnosis, and treatment monitoring. The pharmaceutical industry has concentrated more on medication development, drug pharmacokinetics, and surrogate treatment end points. In the era of personalized medicine, these interests have evolved to a continuum where the knowledge of diagnosis and molecular mechanism of disease from imaging not only guides new medication development but also is beginning to direct individualized drug choice and dosage.

  1. Molecular imaging with CARS micro-spectroscopy.

    PubMed

    Cicerone, Marcus

    2016-08-01

    After more than a decade of instrument and method development, broadband coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy is beginning to live up to its potential as a label-free imaging modality that can rapidly generate high resolution images with full vibrational spectra at each image pixel. Presently these instruments are able to obtain quantitative, spatially resolved information on lipids from the CH stretch region of the Raman spectrum, and some instrument designs facilitate acquisition of high quality fingerprint spectra, containing information on a host of molecular species including structural proteins, nucleotides, and metabolites. While most of the existing instruments are research projects themselves, it appears that the relevant technologies are maturing so that commercially available instruments may not be too far in the future, making this remarkable imaging modality widely available.

  2. 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.

  3. 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

  4. Engineering imaging probes and molecular machines for nanomedicine.

    PubMed

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

    2012-10-01

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

  5. Molecular orbital imaging for partially aligned molecules

    NASA Astrophysics Data System (ADS)

    Qin, Meiyan; Zhu, Xiaosong

    2017-01-01

    We investigate molecular orbital reconstruction using high-order harmonic emissions from partially aligned molecular ensembles. By carrying out the reconstruction procedure using the harmonic sampling with or without the spectral minimum, the roles of the harmonic phase and amplitude modulation due to the partial alignment can be separately studied. It is found that with the prior knowledge of the orbital symmetry, the reconstructed result is very sensitive to the modulation of the harmonic phase for the πg orbital, while in the case of σg orbital, the reconstructed result is mainly determined by the harmonic amplitude. These results can provide an important reference for the future experiment of molecular orbital imaging.

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

    PubMed

    Sevick-Muraca, Eva M; Rasmussen, John C

    2008-01-01

    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.

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

    PubMed

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-02-17

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

  8. 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.

  9. Molecular Imaging of Immunotherapy Targets in Cancer

    PubMed Central

    Ehlerding, Emily B.; England, Christopher G.; McNeel, Douglas G.

    2016-01-01

    Immunotherapy has emerged as a promising alternative in the arsenal against cancer by harnessing the power of the immune system to specifically target malignant tissues. As the field of immunotherapy continues to expand, researchers will require newer methods for studying the interactions between the immune system, tumor cells, and immunotherapy agents. Recently, several noninvasive imaging strategies have been used to map the biodistribution of immune checkpoint molecules, monitor the efficacy and potential toxicities of the treatments, and identify patients who are likely to benefit from immunotherapies. In this review, we outline the current applications of noninvasive techniques for the preclinical imaging of immunotherapy targets and suggest future pathways for molecular imaging to contribute to this developing field. PMID:27469363

  10. Application of ASAP in integral imaging

    NASA Astrophysics Data System (ADS)

    Wang, Hong-xia; Xu, Zhi-li; Wen, Shao-jie; Wu, Chun-hong

    2012-10-01

    Integral imaging (II) is a technique that is capable of displaying 3D images with continuous parallax in full natural color. At present Integral Imaging is a popular three-dimensional imaging technology. It is becoming the most perspective technique in developing next generation three-dimensional TV (3DTV) and visualization field due to its outstanding advantages. The micro-lens array is used in recording and replaying 3D scene information in this technique with true color, simply reconstruction and non-relevant light source. In order to research really many precision instrument are required. But the price is too high to set up a complicated authentic imaging system. In the same time the imaging condition is very difficult to satisfy. ASAP (Advanced System Analysis Program) is an advanced imitates optical software to solve reality optical questions. It is used in many research territories. In this paper the ASAP software is proposed to simulate and model the micro-lens array sheet. The ray tracing and energy distribution is completed. According to the study results we can optimum lens designing through modifying the focal length, aperture size and imaging position. We hope the study cost can be reduced and the efficiency can be improved through the use of simulation method to optical design software ASAP.

  11. Small Animal Imaging Center Design: The Facility at the UCLA Crump Institute for Molecular Imaging

    PubMed Central

    Stout, David B.; Chatziioannou, Arion F.; Lawson, Timothy P.; Silverman, Robert W.; Gambhir, Sanjiv S.; Phelps, Michael E.

    2010-01-01

    Purpose The growing number of mouse and rat experiments, coupled with advances in small-animal imaging systems such as microPET®, optical, microCAT™, microMR, ultrasound and microSPECT, has necessitated a common technical center for imaging small animals. Procedures At the UCLA Crump Institute for Molecular Imaging, we have designed and built a facility to support the research interests of a wide range of investigators from multiple disciplines. Requirements to satisfy both research and regulatory oversight have been critically examined. Support is provided for investigator training, study scheduling, data acquisition, archiving, image display, and analysis. Results The center has been in operation for more than 18 months, supporting more than 13,000 individual imaging procedures. Conclusions We have created a facility that maximizes our resource utilization while providing optimal investigator support, as well as the means to continually improve the quality and diversity of the science by integrating physical and biological sciences. PMID:16261425

  12. Molecular imaging: the vision and opportunity for radiology in the future.

    PubMed

    Hoffman, John M; Gambhir, Sanjiv S

    2007-07-01

    Molecular imaging is being hailed as the next great advance for imaging. This introductory article in the molecular imaging series to be published over the next several months in Radiology sets the stage for the subsequent set of articles by providing relevant definitions and background information and traces the evolution of molecular imaging to its current state of research and clinical practice. It discusses in detail the evolution of molecular imaging and the role that the National Cancer Institute and the National Institutes of Health have had in the funding and development of many of the important molecular imaging research programs that are in existence today. The article also provides basic information about the complex biology of the cell and details of the pathogenesis of cancer and how molecular imaging will be critical for earlier detection and management of cancer in the future. The article lays the foundation for the subsequent articles in the series and describes how and why molecular imaging will be critical and integral for clinical care of patients in the future. The introductory article also discusses the relevance of molecular imaging to clinical radiology practice and why it is critical for the practicing radiologist to understand these evolving techniques, as they will be the future of imaging.

  13. 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.

  14. 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.

  15. Comprehensive phantom for interventional fluorescence molecular imaging

    NASA Astrophysics Data System (ADS)

    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.

  16. Integrated circuit tester using interferometric imaging

    SciTech Connect

    Donaldson, W.R.; Michaels, E.M.R.; Akowuah, K.

    1997-04-01

    An interferometric imaging technique can provide time-resolved diagnostics of semiconductor integrated circuits. The semiconductor device is placed in one arm of an interferometer and illuminated with a picosecond pulse from a sub-bandgap infrared laser. As the laser passes through the semiconductor, it samples local variations in the index of refraction. These variations are caused by a number of physical phenomena including dopants in the material such as those used to form device structures, heating due to the flow of electrical currents, and changes in carrier concentration due to injection. These variations have both static and dynamic components. The dynamic components are associated with the normal device operation and are the most interesting. To separate the components, the device is first imaged in a quiescent state, and then a second image is taken after the device enters a known voltage state. Differences between the two images determine where the local index of refraction has changed and by how much. A third image taken with the reference arm of the interferometer blocked, allows device structures to be associated with particular changes in the index of refraction. Activation of the voltage state is synchronized with the pulsed illumination source, and the time delay between the application of the voltage and the laser probe pulse allows us to take a series of images that map the time evolution of the interferogram. This technique offers an exciting new diagnostic for semiconductor integrated circuits. The technique is noninvasive and compatible with high-speed operation of integrated circuits. The picosecond resolution enables us to either characterize specific logic states or watch an individual device turn on. This imaging technique is sensitive to all of the index of refraction changes that can be associated with IC`s. These include heating due to current flowing through narrow wires and charge injection into the depletion region of a transistor.

  17. Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging.

    PubMed

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

    2010-01-07

    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 is a great deal of interest 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 x 2.4 mm(2) field-of-view. The transverse resolutions of OCT and FMI of the system are both approximately 10 microm. 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 the APC(min) mouse model is presented as an example of biological applications of this co-registered OCT/FMI system.

  18. 3D integral imaging with optical processing

    NASA Astrophysics Data System (ADS)

    Martínez-Corral, Manuel; Martínez-Cuenca, Raúl; Saavedra, Genaro; Javidi, Bahram

    2008-04-01

    Integral imaging (InI) systems are imaging devices that provide auto-stereoscopic images of 3D intensity objects. Since the birth of this new technology, InI systems have faced satisfactorily many of their initial drawbacks. Basically, two kind of procedures have been used: digital and optical procedures. The "3D Imaging and Display Group" at the University of Valencia, with the essential collaboration of Prof. Javidi, has centered its efforts in the 3D InI with optical processing. Among other achievements, our Group has proposed the annular amplitude modulation for enlargement of the depth of field, dynamic focusing for reduction of the facet-braiding effect, or the TRES and MATRES devices to enlarge the viewing angle.

  19. Imaging Total Stations - Modular and Integrated Concepts

    NASA Astrophysics Data System (ADS)

    Hauth, Stefan; Schlüter, Martin

    2010-05-01

    Keywords: 3D-Metrology, Engineering Geodesy, Digital Image Processing Initialized in 2009, the Institute for Spatial Information and Surveying Technology i3mainz, Mainz University of Applied Sciences, forces research towards modular concepts for imaging total stations. On the one hand, this research is driven by the successful setup of high precision imaging motor theodolites in the near past, on the other hand it is pushed by the actual introduction of integrated imaging total stations to the positioning market by the manufacturers Topcon and Trimble. Modular concepts for imaging total stations are manufacturer independent to a large extent and consist of a particular combination of accessory hardware, software and algorithmic procedures. The hardware part consists mainly of an interchangeable eyepiece adapter offering opportunities for digital imaging and motorized focus control. An easy assembly and disassembly in the field is possible allowing the user to switch between the classical and the imaging use of a robotic total station. The software part primarily has to ensure hardware control, but several level of algorithmic support might be added and have to be distinguished. Algorithmic procedures allow to reach several levels of calibration concerning the geometry of the external digital camera and the total station. We deliver insight in our recent developments and quality characteristics. Both the modular and the integrated approach seem to have its individual strengths and weaknesses. Therefore we expect that both approaches might point at different target applications. Our aim is a better understanding of appropriate applications for robotic imaging total stations. First results are presented. Stefan Hauth, Martin Schlüter i3mainz - Institut für Raumbezogene Informations- und Messtechnik FH Mainz University of Applied Sciences Lucy-Hillebrand-Straße 2, 55128 Mainz, Germany

  20. Radiolabeled nanogels for nuclear molecular imaging.

    PubMed

    Singh, Smriti; Bingöl, Bahar; Morgenroth, Agnieszka; Mottaghy, Felix M; Möller, Martin; Schmaljohann, Jörn

    2013-04-12

    An efficient and simple synthesis approach to form stable (68) Ga-labeled nanogels is reported and their fundamental properties investigated. Nanogels are obtained by self-assembly of amphiphilic statistical prepolymers derivatised with chelating groups for radiometals. The resulting nanogels exhibit a well-defined spherical shape with a diameter of 290 ± 50 nm. The radionuclide (68) Ga is chelated in high radiochemical yields in an aqueous medium at room temperature. The phagocytosis assay demonstrates a highly increased internalization of nanogels by activated macrophages. Access to these (68) Ga-nanogels will allow the investigation of general behavior and clearance pathways of nanogels in vivo by nuclear molecular imaging.

  1. Molecular imaging with targeted contrast ultrasound.

    PubMed

    Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

    2009-01-01

    Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation.

  2. 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.

  3. Molecular imaging of human embryonic stem cells.

    PubMed

    Narsinh, Kazim H; Cao, Feng; Wu, Joseph C

    2009-01-01

    Human embryonic stem cells (hESCs) are a renewable source of differentiated cell types that may be employed in various tissue regeneration strategies. However, clinical implementation of cell transplantation therapy is hindered by legitimate concerns regarding the in vivo teratoma formation of undifferentiated hESCs and host immune reactions to allogenic cells. Investigating in vivo hESC behaviour and the ultimate feasibility of cell transplantation therapy necessitates the development of novel molecular imaging techniques to longitudinally monitor hESC localization, proliferation, and viability in living subjects. An innovative approach to harness the respective strengths of various imaging platforms is the creation and use of a fusion reporter construct composed of red fluorescent protein (RFP), firefly luciferase (fluc), and herpes simplex virus thymidine kinase (HSV-tk). The imaging modalities made available by use of this construct, including optical fluorescence, bioluminescence, and positron emission tomography (PET), mat be adapted to investigate a variety of physiological phenomena, including the spatio-temporal kinetics of hESC engraftment and proliferation in living subjects. This chapter describes the applications of reporter gene imaging to accelerate basic science research and clinical studies involving hESCs through (1) isolation of a homogenous hESC population, (2) noninvasive, longitudinal tracking of the location and proliferation of hESCs administered to a living subject, and (3) ablation of the hESC graft in the event of cellular misbehavior.

  4. jAMVLE, a New Integrated Molecular Visualization Learning Environment

    ERIC Educational Resources Information Center

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

    2006-01-01

    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…

  5. All-optically integrated multimodality imaging system: combined photoacoustic microscopy, optical coherence tomography, and fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Chen, Zhongjiang; Yang, Sihua; Xing, Da

    2016-10-01

    We have developed a multimodality imaging system by optically integrating all-optical photoacoustic microscopy (AOPAM), optical coherence tomography (OCT) and fluorescence microscopy (FLM) to provide complementary information including optical absorption, optical back-scattering and fluorescence contrast of biological tissue. By sharing the same low-coherence Michelson interferometer, AOPAM and OCT could be organically optically combined to obtain the absorption and scattering information of the biological tissues. Also, owing to using the same laser source and objective lens, intrinsically registered photoacoustic and fluorescence signals are obtained to present the radiative and nonradiative transition process of absorption. Simultaneously photoacoustic angiography, tissue structure and fluorescence molecular in vivo images of mouse ear were acquired to demonstrate the capabilities of the optically integrated trimodality imaging system, which can present more information to study tumor angiogenesis, vasculature, anatomical structure and microenvironments in vivo.

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

    PubMed

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

    2016-09-15

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

  7. Integrated imaging of neonatal renal masses.

    PubMed

    Kirks, D R; Rosenberg, E R; Johnson, D G; King, L R

    1985-01-01

    Thirty-three neonatal renal masses were evaluated during a 2-year interval. The final diagnoses in these 33 patients were hydronephrosis [14], multicystic dysplastic kidney [10], renal vein thrombosis [3], obstructed upper pole duplication [2], polycystic kidney disease [2], nephroblastomatosis [1], and mesoblastic nephroma [1]. We recommend an integrated imaging approach that utilizes sonography to clarify anatomy and renal scintigraphy or excretory urography to determine renal function.

  8. Molecular imaging and cancer gene therapy.

    PubMed

    Saadatpour, Z; Bjorklund, G; Chirumbolo, S; Alimohammadi, M; Ehsani, H; Ebrahiminejad, H; Pourghadamyari, H; Baghaei, B; Mirzaei, H R; Sahebkar, A; Mirzaei, H; Keshavarzi, M

    2016-11-18

    Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers. Imaging techniques have been critical in guiding physicians in the more accurate and precise diagnosis and monitoring of cancer patients in different phases of malignancies. Imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are non-invasive and powerful tools for monitoring of the distribution of transgene expression over time and assessing patients who have received therapeutic genes. Here, we discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients' response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals.Cancer Gene Therapy advance online publication, 18 November 2016; doi:10.1038/cgt.2016.62.

  9. Intraoperative molecular imaging to identify lung adenocarcinomas

    PubMed Central

    Newton, Andrew D.; Kennedy, Gregory T.; Predina, Jarrod D.; Low, Philip S.

    2016-01-01

    Intraoperative molecular imaging is a promising new technology with numerous applications in lung cancer surgery. Accurate identification of small nodules and assessment of tumor margins are two challenges in pulmonary resections for cancer, particularly with increasing use of video-assisted thoracoscopic surgery (VATS). One potential solution to these problems is intraoperative use of a fluorescent contrast agent to improve detection of cancer cells. This technology requires both a targeted fluorescent dye that will selectively accumulate in cancer cells and a specialized imaging system to detect the cells. In several studies, we have shown that intraoperative imaging with indocyanine green (ICG) can be used to accurately identify indeterminate pulmonary nodules. The use of a folate-tagged fluorescent molecule targeted to the folate receptor-α (FRα) further improves the sensitivity and specificity of detecting lung adenocarcinomas. We have demonstrated this technology can be used as an “optical biopsy” to differentiate adenocarcinoma versus other histological subtypes of pulmonary nodules. This strategy has potential applications in assessing bronchial stump margins, identifying synchronous or metachronous lesions, and rapidly assessing lymph nodes for lung adenocarcinoma. PMID:28066672

  10. Image reconstruction for synchronous data acquisition in fluorescence molecular tomography.

    PubMed

    Zhang, Xuanxuan; Liu, Fei; Zuo, Siming; Bai, Jing; Luo, Jianwen

    2015-01-01

    The present full-angle, free-space fluorescence molecular tomography (FMT) system uses a step-by-step strategy to acquire measurements, which consumes time for both the rotation of the object and the integration of the charge-coupled device (CCD) camera. Completing the integration during the rotation is a more time-efficient strategy called synchronous data acquisition. However, the positions of sources and detectors in this strategy are not stationary, which is not taken into account in the conventional reconstruction algorithm. In this paper we propose a reconstruction algorithm based on the finite element method (FEM) to overcome this problem. Phantom experiments were carried out to validate the performance of the algorithm. The results show that, compared with the conventional reconstruction algorithm used in the step-by-step data acquisition strategy, the proposed algorithm can reconstruct images with more accurate location data and lower relative errors when used with the synchronous data acquisition strategy.

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

    SciTech Connect

    Bohn, Paul W.; Shrout, J. D.; Sweedler, J. V.; Farrand, S.

    2016-01-25

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

  12. 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

  13. 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.

  14. 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

  15. Ultrasound Molecular Imaging and Drug Delivery.

    PubMed

    Caskey, Charles F

    2017-03-02

    Ultrasound is a rapidly advancing field with many emerging diagnostic and therapeutic applications. For diagnostics, new vascular targets are routinely identified and mature technologies are being translated to humans, while other recent innovations may bring about the creation of acoustic reporter genes and micron-scale resolution with ultrasound. As a cancer therapy, ultrasound is being explored as an adjuvant to immune therapies and to deliver acoustically or thermally active drugs to tumor regions. Ultrasound-enhanced delivery across the blood brain barrier (BBB) could potentially be very impactful for brain cancers and neurodegenerative diseases where the BBB often impedes the delivery of therapeutic molecules. In this minireview, we provide an overview of these topics in the field of ultrasound that are especially relevant to the interests of World Molecular Imaging Society.

  16. 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

  17. 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

  18. Molecular mechanisms of retroviral integration site selection

    PubMed Central

    Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

    2014-01-01

    Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

  19. 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.

  20. Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.

    PubMed

    Lee, Chung-Cheng; Sui, Guodong; Elizarov, Arkadij; Shu, Chengyi Jenny; Shin, Young-Shik; Dooley, Alek N; Huang, Jiang; Daridon, Antoine; Wyatt, Paul; Stout, David; Kolb, Hartmuth C; Witte, Owen N; Satyamurthy, Nagichettiar; Heath, James R; Phelps, Michael E; Quake, Stephen R; Tseng, Hsian-Rong

    2005-12-16

    Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.

  1. Translational research of optical molecular imaging for personalized medicine.

    PubMed

    Qin, C; Ma, X; Tian, J

    2013-12-01

    In the medical imaging field, molecular imaging is a rapidly developing discipline and forms many imaging modalities, providing us effective tools to visualize, characterize, and measure molecular and cellular mechanisms in complex biological processes of living organisms, which can deepen our understanding of biology and accelerate preclinical research including cancer study and medicine discovery. Among many molecular imaging modalities, although the penetration depth of optical imaging and the approved optical probes used for clinics are limited, it has evolved considerably and has seen spectacular advances in basic biomedical research and new drug development. With the completion of human genome sequencing and the emergence of personalized medicine, the specific drug should be matched to not only the right disease but also to the right person, and optical molecular imaging should serve as a strong adjunct to develop personalized medicine by finding the optimal drug based on an individual's proteome and genome. In this process, the computational methodology and imaging system as well as the biomedical application regarding optical molecular imaging will play a crucial role. This review will focus on recent typical translational studies of optical molecular imaging for personalized medicine followed by a concise introduction. Finally, the current challenges and the future development of optical molecular imaging are given according to the understanding of the authors, and the review is then concluded.

  2. 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

  3. Click Reaction: An Applicable Radiolabeling Method for Molecular Imaging.

    PubMed

    Choi, Ji Young; Lee, Byung Chul

    2015-12-01

    In recent years, the click reaction has found rapidly growing applications in the field of radiochemistry, ranging from a practical labeling method to molecular imaging of biomacromolecules. This present review details the development of highly reliable, powerful and selective click chemistry reactions for the rapid synthesis of new radiotracers for molecular imaging.

  4. Integrating image data into biomedical text categorization.

    PubMed

    Shatkay, Hagit; Chen, Nawei; Blostein, Dorothea

    2006-07-15

    Categorization of biomedical articles is a central task for supporting various curation efforts. It can also form the basis for effective biomedical text mining. Automatic text classification in the biomedical domain is thus an active research area. Contests organized by the KDD Cup (2002) and the TREC Genomics track (since 2003) defined several annotation tasks that involved document classification, and provided training and test data sets. So far, these efforts focused on analyzing only the text content of documents. However, as was noted in the KDD'02 text mining contest-where figure-captions proved to be an invaluable feature for identifying documents of interest-images often provide curators with critical information. We examine the possibility of using information derived directly from image data, and of integrating it with text-based classification, for biomedical document categorization. We present a method for obtaining features from images and for using them-both alone and in combination with text-to perform the triage task introduced in the TREC Genomics track 2004. The task was to determine which documents are relevant to a given annotation task performed by the Mouse Genome Database curators. We show preliminary results, demonstrating that the method has a strong potential to enhance and complement traditional text-based categorization methods.

  5. Medium scale integration of molecular logic gates in an automaton.

    PubMed

    Macdonald, Joanne; Li, Yang; Sutovic, Marko; Lederman, Harvey; Pendri, Kiran; Lu, Wanhong; Andrews, Benjamin L; Stefanovic, Darko; Stojanovic, Milan N

    2006-11-01

    The assembly of molecular automata that perform increasingly complex tasks, such as game playing, presents an unbiased test of molecular computation. We now report a second-generation deoxyribozyme-based automaton, MAYA-II, which plays a complete game of tic-tac-toe according to a perfect strategy. In silicon terminology, MAYA-II represents the first "medium-scale integrated molecular circuit", integrating 128 deoxyribozyme-based logic gates, 32 input DNA molecules, and 8 two-channel fluorescent outputs across 8 wells.

  6. 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

  7. Symplectic integrator for molecular dynamics of a protein in water

    NASA Astrophysics Data System (ADS)

    Ishida, Hisashi; Nagai, Yoshinori; Kidera, Akinori

    1998-01-01

    The symplectic integrator is an algorithm for solving equations of motion, preserving the volume in phase space and ensuring a stable simulation. We carried out molecular dynamics simulations of liquid water and a protein in water using several variations of symplectic integrators. It was found that a fourth-order symplectic integrator of Calvo and Sanz-Serna generated a trajectory of much higher accuracy than the conventional Verlet and Gear methods with the same requirements for CPU time.

  8. JIVE integration of imaging and behavioral data.

    PubMed

    Yu, Qunqun; Risk, Benjamin B; Zhang, Kai; Marron, J S

    2017-02-27

    A major goal in neuroscience is to understand the neural pathways underlying human behavior. We introduce the recently developed Joint and Individual Variation Explained (JIVE) method to the neuroscience community to simultaneously analyze imaging and behavioral data from the Human Connectome Project. Motivated by recent computational and theoretical improvements in the JIVE approach, we simultaneously explore the joint and individual variation between and within imaging and behavioral data. In particular, we demonstrate that JIVE is an effective and efficient approach for integrating task fMRI and behavioral variables using three examples: one example where task variation is strong, one where task variation is weak and a reference case where the behavior is not directly related to the image. These examples are provided to visualize the different levels of signal found in the joint variation including working memory regions in the image data and accuracy and response time from the in-task behavioral variables. Joint analysis provides insights not available from conventional single block decomposition methods such as Singular Value Decomposition. Additionally, the joint variation estimated by JIVE appears to more clearly identify the working memory regions than Partial Least Squares (PLS), while Canonical Correlation Analysis (CCA) gives grossly overfit results. The individual variation in JIVE captures the behavior unrelated signals such as a background activation that is spatially homogeneous and activation in the default mode network. The information revealed by this individual variation is not examined in traditional methods such as CCA and PLS. We suggest that JIVE can be used as an alternative to PLS and CCA to improve estimation of the signal common to two or more datasets and reveal novel insights into the signal unique to each dataset.

  9. Molecular imaging in Libman-Sacks endocarditis.

    PubMed

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

    2015-04-01

    We present a 54-year-old woman with systemic lupus erythematosus (SLE), fever, pericardial effusion and a mitral valve vegetation. (18)F-Fluorodesoxyglucose positron emission tomography CT ((18)F-FDG-PET-CT) showed very high accumulation of the isotope at the mitral valve. The patient underwent cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, (18)F-FDG-PET-CT clearly demonstrated the increased glucose uptake caused by infiltrating white blood cells in the ongoing inflammatory process at the mitral valve. In conclusion, (18)F-FDG-PET-CT cannot be used to distinguish between IE and non-infective Libman-Sacks vegetations.

  10. Multiscale integration of -omic, imaging, and clinical data in biomedical informatics.

    PubMed

    Phan, John H; Quo, Chang F; Cheng, Chihwen; Wang, May Dongmei

    2012-01-01

    This paper reviews challenges and opportunities in multiscale data integration for biomedical informatics. Biomedical data can come from different biological origins, data acquisition technologies, and clinical applications. Integrating such data across multiple scales (e.g., molecular, cellular/tissue, and patient) can lead to more informed decisions for personalized, predictive, and preventive medicine. However, data heterogeneity, community standards in data acquisition, and computational complexity are big challenges for such decision making. This review describes genomic and proteomic (i.e., molecular), histopathological imaging (i.e., cellular/tissue), and clinical (i.e., patient) data; it includes case studies for single-scale (e.g., combining genomic or histopathological image data), multiscale (e.g., combining histopathological image and clinical data), and multiscale and multiplatform (e.g., the Human Protein Atlas and The Cancer Genome Atlas) data integration. Numerous opportunities exist in biomedical informatics research focusing on integration of multiscale and multiplatform data.

  11. Nanoparticle Functionalization and Its Potentials for Molecular Imaging

    PubMed Central

    Thiruppathi, Rukmani; Mishra, Sachin; Ganapathy, Mathangi

    2016-01-01

    Functionalization enhances the properties and characteristics of nanoparticles through surface modification, and enables them to play a major role in the field of medicine. In molecular imaging, quality functional images are required with proper differentiation which can be seen with high contrast to obtain viable information. This review article discusses how functionalization enhances molecular imaging and enables multimodal imaging by which images with combination of functions particular to each modality can be obtained. This also explains how nanoparticles interacting at molecular level, when functionalized with molecules can target the cells of interest or substances with high specificity, reducing background signal and allowing simultaneous therapies to be carried out while imaging. Functionalization allows imaging for a prolonged period and enables to track the cells over a period of time. Recent researches and progress in functionalizing the nanoparticles to specifically enhance bioimaging with different modalities and their applications are reviewed in this article. PMID:28331783

  12. Instrumentation and probes for molecular and cellular imaging.

    PubMed

    Lecchi, M; Ottobrini, L; Martelli, C; Del Sole, A; Lucignani, G

    2007-06-01

    Molecular and cellular imaging is a branch of biomedical sciences that combines the use of imaging instrumentation and biotechnology to characterize molecular and cellular processes in living organisms in normal and pathologic conditions. The two merging areas of research behind molecular and cellular imaging are detection technology, i.e. scanners and imaging devices, and development of tracers, contrast agents and reporter probes that make imaging with scanners and devices possible. Several in vivo imaging instruments currently used in human studies, such as computer tomography, ultrasound, magnetic resonance, positron emission tomography and single photon emission computed tomography, have been rescaled for small animal studies, while other methods initially used for in vitro evaluation, such as bioluminescence and fluorescence, have been refined for in vivo imaging. Conventional imaging relies on the use of non specific contrast agents and classical probes; however, newly developed targeted contrast agents and activable ''smart'' imaging probes for so-called ''targeted imaging'' have demonstrated high specificity and high signal to noise ratio in small animal studies. This review focuses on basic recent findings in the technical aspects of molecular and cellular imaging modalities (equipment, targeted probe and contrast agents and applied combinations of instrumentation and probe) with particular attention to the choice of the future: the multimodal imaging approach.

  13. Ultrasound for molecular imaging and therapy in cancer

    PubMed Central

    Kaneko, Osamu F.

    2012-01-01

    Over the past decade, molecularly-targeted contrast enhanced ultrasound (ultrasound molecular imaging) has attracted significant attention in preclinical research of cancer diagnostic and therapy. Potential applications for ultrasound molecular imaging run the gamut from early detection and characterization of malignancies to monitoring treatment responses and guiding therapies. There may also be a role for ultrasound contrast agents for improved delivery of chemotherapeutic drugs and gene therapies across biological barriers. Currently, a first Phase 0 clinical trial in patients with prostate cancer assesses toxicity and feasibility of ultrasound molecular imaging using contrast agents targeted at the angiogenic marker vascular endothelial growth factor receptor type 2 (VEGFR2). This mini-review highlights recent advances and potential applications of ultrasound molecular imaging and ultrasound-guided therapy in cancer. PMID:23061039

  14. 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.

  15. 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.

  16. Molecular characterization of rheumatoid arthritis with magnetic resonance imaging.

    PubMed

    Gu, Jeffrey T; Nguyen, Linda; Chaudhari, Abhijit J; MacKenzie, John D

    2011-04-01

    Several recent advances in the field of magnetic resonance imaging (MRI) may transform the detection and monitoring of rheumatoid arthritis (RA). These advances depict both anatomic and molecular alterations from RA. Previous techniques could detect specific end products of metabolism in vitro or were limited to providing anatomic information. This review focuses on the novel molecular imaging techniques of hyperpolarized carbon-13 MRI, MRI with iron-labeled probes, and fusion of MRI with positron emission tomography. These new imaging approaches go beyond the anatomic description of RA and lend new information into the status of this disease by giving molecular information.

  17. Molecular Imaging and Therapy of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    Our objective is to develop an arsenic-based radiopharmaceutical platform for IGF1R-targeted imaging and therapy of PCa. The hypothesis is that...arsenic-based, IGF1R-targeted radiopharmaceuticals can allow for PET imaging, IRT, and monitoring the therapeutic response of PCa. Specific Aims: Aim 1: To...models with PET imaging. Aim 3: To monitor the efficacy of 76As-based IRT of PCa with multimodality imaging.

  18. 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

  19. 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.

  20. Components of a curriculum for molecular imaging scientists.

    PubMed

    Zinn, Kurt R; Anderson, Carolyn J; Bradbury, Michelle; Cutler, Cathy S; Peterson, Todd E; Morgan, Desiree E; Price, Julie C; Graham, Michael M; Contag, Christopher H; Wittstrom, Kristina; Norenberg, Jeffrey P

    2011-04-01

    Molecular imaging is the visualization, characterization, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems (1). It comprises an emerging set of technologies that builds on advances in imaging procedures (e.g., PET, SPECT, MRI, ultrasound, optical, and photoacoustic), improved understanding of biology, and the development of molecularly targeted agents. These continuously expanding sets of imaging methods are often used in combination, and advances in data acquisition and analyses facilitate a more complete understanding of biology. Molecular imaging aims to improve our understanding of mammalian biology and lead to advances in patient care by providing targeted therapies that will enable personalized medicine and the imaging tools to assess outcome. Implementation of these new technologies in clinical care has many educational, technical, and regulatory challenges that must be overcome before molecular imaging reaches its full potential. The impact of molecular imaging has been significant in several disciplines, because it represents a paradigm shift in how scientists and clinicians can observe biology in real time and in a relatively noninvasive manner to enable the power of repeated measures in living organisms.

  1. Pixel extraction based integral imaging with controllable viewing direction

    NASA Astrophysics Data System (ADS)

    Ji, Chao-Chao; Deng, Huan; Wang, Qiong-Hua

    2012-09-01

    We propose pixel extraction based integral imaging with a controllable viewing direction. The proposed integral imaging can provide viewers three-dimensional (3D) images in a very small viewing angle. The viewing angle and the viewing direction of the reconstructed 3D images are controlled by the pixels extracted from an elemental image array. Theoretical analysis and a 3D display experiment of the viewing direction controllable integral imaging are carried out. The experimental results verify the correctness of the theory. A 3D display based on the integral imaging can protect the viewer’s privacy and has huge potential for a television to show multiple 3D programs at the same time.

  2. 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.

  3. Variational path integral molecular dynamics study of a water molecule

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi

    2013-08-01

    In the present study, a variational path integral molecular dynamics method developed by the author [Chem. Phys. Lett. 482, 165 (2009)] is applied to a water molecule on the adiabatic potential energy surface. The method numerically generates an exact wavefunction using a trial wavefunction of the target system. It has been shown that even if a poor trial wavefunction is employed, the exact quantum distribution is numerically extracted, demonstrating the robustness of the variational path integral method.

  4. Quantum tunneling splittings from path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

  5. 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

  6. ESPMIS: Helping Young Scientists Navigate the Molecular Imaging Landscape.

    PubMed

    Zeglis, Brian M; Vugts, Danielle J

    2017-02-13

    The core mission of the Early Stage Professionals in Molecular Imaging Sciences (ESPMIS) Interest Group is to help young scientists navigate the professional landscape of molecular imaging. Since its formation in early 2015, ESPMIS has used the annual World Molecular Imaging Congress (WMIC) as a platform to provide education and guidance on three areas that are particularly critical to young scientists: networking, career development, and funding. In the coming years, ESPMIS plans to continue its focus on these topics, work with the WMIS on the creation of new digital tools for young scientists, and introduce two new areas of emphasis: the importance of mentoring and international career opportunities. We at ESPMIS sincerely believe that the future is bright for young scientists in molecular imaging, and we are here to help.

  7. Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

    PubMed Central

    Zhang, Hong; Tian, Mei

    2013-01-01

    Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB), in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI), nuclear medicine imaging, and optical imaging (OI). Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke. PMID:24222920

  8. 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.

  9. Emerging concepts in functional and molecular photoacoustic imaging.

    PubMed

    Hu, Song

    2016-08-01

    Providing the specific imaging contrast of optical absorption and excellent spatial scalability across the optical and ultrasonic dimensions, photoacoustic imaging has been rapidly emerging and expanding in the past two decades. In this review, I focus on a few latest advances in this enabling technology that hold the potential to transform in vivo functional and molecular imaging at multiple length scales. Specifically, multi-parametric photoacoustic microscopy enables simultaneous high-resolution mapping of hemoglobin concentration, oxygen saturation and blood flow-opening up the possibility of quantifying the metabolic rate of oxygen at the microscopic level. The pump-probe approach harnesses a variety of photoinduced transient optical absorption as novel contrast mechanisms for high-specificity molecular imaging at depth and as nonlinear excitation strategies for high-resolution volumetric microscopy beyond the conventional limit. Novel magneto-optical and photochromic probes lead to contrast-enhanced molecular photoacoustic imaging through differential detection.

  10. 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

  11. 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

  12. 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

  13. Photoacoustic molecular imaging of small animals in vivo

    NASA Astrophysics Data System (ADS)

    Xie, Xueyi; Li, Meng-Lin; Oh, Jung-Taek; Ku, Geng; Wang, Wei; Li, Chun; Similache, Sergiu; Lungu, Gina F.; Stoica, George; Wang, Lihong V.

    2006-02-01

    Molecular imaging is a newly emerging field in which the modern tools of molecular and cell biology have been married to state-of-the-art technologies for noninvasive imaging. The study of molecular imaging will lead to better methods for understanding biological processes as well as diagnosing and managing disease. Here we present noninvasive in vivo spectroscopic photoacoustic tomography (PAT)-based molecular imaging of αvβ3 integrin in a nude mouse U87 brain tumor. PAT combines high optical absorption contrast and high ultrasonic resolution by employing short laser pulses to generate acoustic waves in biological tissues through thermoelastic expansion. Spectroscopic PAT-based molecular imaging offers the separation of the contributions from different absorbers based on the differences in optical absorption spectra among those absorbers. In our case, in the near infrared (NIR) range, oxy-heamoglobin (O2Hb), deoxy-heamoglobin (HHb) and the injected αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent are the three main absorbers. Therefore, with the excitation by multiple wavelength laser pulses, spectroscopic PAT-based molecular imaging not only provides the level of the contrast agent accumulation in the U87 glioblastoma tumor, which is related to the metabolism and angiogenesis of the tumor, but also offers the information on tumor angiogenesis and tumor hypoxia.

  14. Progresses in 3D integral imaging with optical processing

    NASA Astrophysics Data System (ADS)

    Martínez-Corral, Manuel; Martínez-Cuenca, Raúl; Saavedra, Genaro; Navarro, Héctor; Pons, Amparo; Javidi, Bahram

    2008-11-01

    Integral imaging is a promising technique for the acquisition and auto-stereoscopic display of 3D scenes with full parallax and without the need of any additional devices like special glasses. First suggested by Lippmann in the beginning of the 20th century, integral imaging is based in the intersection of ray cones emitted by a collection of 2D elemental images which store the 3D information of the scene. This paper is devoted to the study, from the ray optics point of view, of the optical effects and interaction with the observer of integral imaging systems.

  15. 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

  16. Integrating molecular diagnostics into histopathology training: the Belfast model.

    PubMed

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information.

  17. 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.

  18. 3D integral imaging using diffractive Fresnel lens arrays.

    PubMed

    Hain, Mathias; von Spiegel, Wolff; Schmiedchen, Marc; Tschudi, Theo; Javidi, Bahram

    2005-01-10

    We present experimental results with binary amplitude Fresnel lens arrays and binary phase Fresnel lens arrays used to implement integral imaging systems. Their optical performance is compared with high quality refractive microlens arrays and pinhole arrays in terms of image quality, color distortion and contrast. Additionally, we show the first experimental results of lens arrays with different focal lengths in integral imaging, and discuss their ability to simultaneously increase both the depth of focus and the field of view.

  19. Molecular Imaging in Cardiovascular Magnetic Resonance Imaging: Current Perspective and Future Potential

    PubMed Central

    Sosnovik, David E.

    2008-01-01

    The development of novel imaging agents and techniques is allowing some biological events to be imaged in vivo with magnetic resonance imaging (MRI) at the cellular and subcellular level. In this paper, the use of novel gadolinium chelates and superparamagnetic iron oxide nanoparticles for molecular MRI of the cardiovascular system is extensively reviewed. The physical properties of these imaging agents and the pulse sequences best suited to their visualization are extensively discussed. The application of molecular MRI in diseases of the vasculature and myocardium is then reviewed. The clinical experience to date, as well as the promise and potential impact of molecular MRI, is extensively discussed. PMID:18690161

  20. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis

    PubMed Central

    Thukkani, Arun K; Jaffer, Farouc A

    2013-01-01

    Novel imaging modalities are required to better identify vulnerable atherosclerotic plaques before their dire consequences of myocardial infarction, sudden death, and stroke. Moving beyond traditional diagnostic methods, the field of molecular imaging offers an innovative approach to report upon critical in vivo biological features of high-risk plaques. Molecular imaging employs engineered, targeted imaging agents in conjunction with sophisticated, high-resolution detection systems. While various modalities have been investigated for this purpose, intravascular near infrared fluorescence imaging (NIRF) strategies are uniquely poised to provide high-resolution readouts of human coronary artery plaques. To date, preclinical animal studies have demonstrated feasibility of both standalone NIRF intravascular imaging as well as dual-modality approaches detecting inflammation and fibrin deposition in coronary-sized arteries. This translatable catheter-based approach is positioned to advance the identification of biologically vulnerable coronary plaques and coronary stents at risk of thrombosis. PMID:23638334

  1. Gold nanoshell bioconjugates for molecular imaging in living cells

    NASA Astrophysics Data System (ADS)

    Loo, Christopher; Hirsch, Leon; Lee, Min-Ho; Chang, Emmanuel; West, Jennifer; Halas, Naomi; Drezek, Rebekah

    2005-05-01

    Advances in scattering-based optical imaging technologies offer a new approach to noninvasive point-of-care detection, diagnosis, and monitoring of cancer. Emerging photonics technologies provide a cost-effective means to image tissue in vivo with high resolution in real time. Advancing the clinical potential of these imaging strategies requires the development of optical contrast agents targeted to specific molecular signatures of disease. We describe the use of a novel class of contrast agents based on nanoshell bioconjugates for molecular imaging in living cells. Nanoshells offer significant advantages over conventional imaging probes including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. We show that nanoshell bioconjugates can be used to effectively target and image human epidermal growth factor receptor 2 (HER2), a clinically relevant biomarker, in live human breast carcinoma cells.

  2. 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.

  3. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    DTIC Science & Technology

    2008-07-01

    vivo imaging of tumors with micron resolution in order to provide a new microscopic, high resolution imaging modality to complement the low resolution...useful approach to delineating the extent of tumors , these methods offer only low resolution, non-specific issues of tissue and cannot provide a detailed...picture of the molecular profile of a tumor . In addition, techniques such as x-ray imaging and MRI are not able to detect small early cancers or

  4. Processing of Image Data by Integrated Circuits

    NASA Technical Reports Server (NTRS)

    Armstrong, R. W.

    1985-01-01

    Sensors combined with logic and memory circuitry. Cross-correlation of two inputs accomplished by transversal filter. Position of image taken to point where image and template data yield maximum value correlation function. Circuit used for controlling robots, medical-image analysis, automatic vehicle guidance, and precise pointing of scientific cameras.

  5. Molecular imaging true-colour spectroscopic optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Robles, Francisco E.; Wilson, Christy; Grant, Gerald; Wax, Adam

    2011-12-01

    Molecular imaging holds a pivotal role in medicine due to its ability to provide invaluable insight into disease mechanisms at molecular and cellular levels. To this end, various techniques have been developed for molecular imaging, each with its own advantages and disadvantages. For example, fluorescence imaging achieves micrometre-scale resolution, but has low penetration depths and is mostly limited to exogenous agents. Here, we demonstrate molecular imaging of endogenous and exogenous chromophores using a novel form of spectroscopic optical coherence tomography. Our approach consists of using a wide spectral bandwidth laser source centred in the visible spectrum, thereby allowing facile assessment of haemoglobin oxygen levels, providing contrast from readily available absorbers, and enabling true-colour representation of samples. This approach provides high spectral fidelity while imaging at the micrometre scale in three dimensions. Molecular imaging true-colour spectroscopic optical coherence tomography (METRiCS OCT) has significant implications for many biomedical applications including ophthalmology, early cancer detection, and understanding fundamental disease mechanisms such as hypoxia and angiogenesis.

  6. 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.

  7. Methods to monitor gene therapy with molecular imaging.

    PubMed

    Waerzeggers, Yannic; Monfared, Parisa; Viel, Thomas; Winkeler, Alexandra; Voges, Jürgen; Jacobs, Andreas H

    2009-06-01

    Recent progress in scientific and clinical research has made gene therapy a promising option for efficient and targeted treatment of several inherited and acquired disorders. One of the most critical issues for ensuring success of gene-based therapies is the development of technologies for non-invasive monitoring of the distribution and kinetics of vector-mediated gene expression. In recent years many molecular imaging techniques for safe, repeated and high-resolution in vivo imaging of gene expression have been developed and successfully used in animals and humans. In this review molecular imaging techniques for monitoring of gene therapy are described and specific use of these methods in the different steps of a gene therapy protocol from gene delivery to assessment of therapy response is illustrated. Linking molecular imaging (MI) to gene therapy will eventually help to improve the efficacy and safety of current gene therapy protocols for human application and support future individualized patient treatment.

  8. 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.

  9. Three-dimensional integral imaging display system via off-axially distributed image sensing

    NASA Astrophysics Data System (ADS)

    Piao, Yongri; Qu, Hongjia; Zhang, Miao; Cho, Myungjin

    2016-10-01

    In this paper, we propose a three-dimensional integral imaging display system with a multiple recorded images using off-axially distributed image sensing. First, the depth map of the 3D objects is extracted from the off-axially recorded multi-perspective 2D images by using profilometry technique. Then, the elemental image array is computationally synthesized using the extracted depth map based on ray mapping model. Finally, the 3D images are optically displayed in integral imaging system. To show the feasibility of the proposed method, the optical experiments for 3D objects are carried out and presented in this paper.

  10. Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

    PubMed Central

    Madden, David J.; Bennett, Ilana J.; Song, Allen W.

    2009-01-01

    The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior-posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application. PMID:19705281

  11. The integration of 3-D cell printing and mesoscopic fluorescence molecular tomography of vascular constructs within thick hydrogel scaffolds.

    PubMed

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

    2012-07-01

    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 ≈ 3 mm). 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.

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

    PubMed

    Carnicer, Artur; Javidi, Bahram

    2015-03-09

    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.

  13. Integration of molecular network data reconstructs Gene Ontology

    PubMed Central

    Gligorijević, Vladimir; Janjić, Vuk; Pržulj, Nataša

    2014-01-01

    Motivation: Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data. Results: We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers’ yeasts protein–protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling. Availability and implementation: Supplementary Tables of new GO

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

    DTIC Science & Technology

    2012-07-01

    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...molecular imaging 7 cdrescher@fhcrc.org Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early Page 3...Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early Charles W Drescher, MD, Principle Investigator

  15. 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.

  16. An integrative characterization of recurrent molecular aberrations in glioblastoma genomes.

    PubMed

    Sintupisut, Nardnisa; Liu, Pei-Ling; Yeang, Chen-Hsiang

    2013-10-01

    Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Decades of investigations and the recent effort of the Cancer Genome Atlas (TCGA) project have mapped many molecular alterations in GBM cells. Alterations on DNAs may dysregulate gene expressions and drive malignancy of tumors. It is thus important to uncover causal and statistical dependency between 'effector' molecular aberrations and 'target' gene expressions in GBMs. A rich collection of prior studies attempted to combine copy number variation (CNV) and mRNA expression data. However, systematic methods to integrate multiple types of cancer genomic data-gene mutations, single nucleotide polymorphisms, CNVs, DNA methylations, mRNA and microRNA expressions and clinical information-are relatively scarce. We proposed an algorithm to build 'association modules' linking effector molecular aberrations and target gene expressions and applied the module-finding algorithm to the integrated TCGA GBM data sets. The inferred association modules were validated by six tests using external information and datasets of central nervous system tumors: (i) indication of prognostic effects among patients; (ii) coherence of target gene expressions; (iii) retention of effector-target associations in external data sets; (iv) recurrence of effector molecular aberrations in GBM; (v) functional enrichment of target genes; and (vi) co-citations between effectors and targets. Modules associated with well-known molecular aberrations of GBM-such as chromosome 7 amplifications, chromosome 10 deletions, EGFR and NF1 mutations-passed the majority of the validation tests. Furthermore, several modules associated with less well-reported molecular aberrations-such as chromosome 11 CNVs, CD40, PLXNB1 and GSTM1 methylations, and mir-21 expressions-were also validated by external information. In particular, modules constituting trans-acting effects with chromosome 11 CNVs and cis-acting effects with chromosome

  17. PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS FOR PROTEIN FUNCTION PREDICTION

    PubMed Central

    Wang, Sheng; Qu, Meng

    2016-01-01

    Automated annotation of protein function has become a critical task in the post-genomic era. Network-based approaches and homology-based approaches have been widely used and recently tested in large-scale community-wide assessment experiments. It is natural to integrate network data with homology information to further improve the predictive performance. However, integrating these two heterogeneous, high-dimensional and noisy datasets is non-trivial. In this work, we introduce a novel protein function prediction algorithm ProSNet. An integrated heterogeneous network is first built to include molecular networks of multiple species and link together homologous proteins across multiple species. Based on this integrated network, a dimensionality reduction algorithm is introduced to obtain compact low-dimensional vectors to encode proteins in the network. Finally, we develop machine learning classification algorithms that take the vectors as input and make predictions by transferring annotations both within each species and across different species. Extensive experiments on five major species demonstrate that our integration of homology with molecular networks substantially improves the predictive performance over existing approaches. PMID:27896959

  18. Ab initio Path Integral Molecular Dynamics Based on Fragment Molecular Orbital Method

    NASA Astrophysics Data System (ADS)

    Fujita, Takatoshi; Watanabe, Hirofumi; Tanaka, Shigenori

    2009-10-01

    We have developed an ab initio path integral molecular dynamics method based on the fragment molecular orbital method. This “FMO-PIMD” method can treat both nuclei and electrons quantum mechanically, and is useful to simulate large hydrogen-bonded systems with high accuracy. After a benchmark calculation for water monomer, water trimer and glycine pentamer have been studied using the FMO-PIMD method to investigate nuclear quantum effects on structure and molecular interactions. The applicability of the present approach is demonstrated through a number of test calculations.

  19. Molecular imaging. A new approach to nuclear cardiology.

    PubMed

    Dobrucki, L W; Sinusas, A J

    2005-03-01

    Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk stratification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentation will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutic angiogenesis.

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

    PubMed

    Put, Stéphanie; Westhovens, René; Lahoutte, Tony; Matthys, Patrick

    2014-04-15

    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.

  1. Direct Imaging of Laser-driven Ultrafast Molecular Rotation.

    PubMed

    Mizuse, Kenta; Fujimoto, Romu; Mizutani, Nobuo; Ohshima, Yasuhiro

    2017-02-04

    We present a method for visualizing laser-induced, ultrafast molecular rotational wave packet dynamics. We have developed a new 2-dimensional Coulomb explosion imaging setup in which a hitherto-impractical camera angle is realized. In our imaging technique, diatomic molecules are irradiated with a circularly polarized strong laser pulse. The ejected atomic ions are accelerated perpendicularly to the laser propagation. The ions lying in the laser polarization plane are selected through the use of a mechanical slit and imaged with a high-throughput, 2-dimensional detector installed parallel to the polarization plane. Because a circularly polarized (isotropic) Coulomb exploding pulse is used, the observed angular distribution of the ejected ions directly corresponds to the squared rotational wave function at the time of the pulse irradiation. To create a real-time movie of molecular rotation, the present imaging technique is combined with a femtosecond pump-probe optical setup in which the pump pulses create unidirectionally rotating molecular ensembles. Due to the high image throughput of our detection system, the pump-probe experimental condition can be easily optimized by monitoring a real-time snapshot. As a result, the quality of the observed movie is sufficiently high for visualizing the detailed wave nature of motion. We also note that the present technique can be implemented in existing standard ion imaging setups, offering a new camera angle or viewpoint for the molecular systems without the need for extensive modification.

  2. Ultrafast molecular orbital imaging based on attosecond photoelectron diffraction.

    PubMed

    Li, Yang; Qin, Meiyan; Zhu, Xiaosong; Zhang, Qingbin; Lan, Pengfei; Lu, Peixiang

    2015-04-20

    We present ab initio numerical study of ultrafast ionization dynamics of H(2)(+) as well as CO(2) and N(2) exposed to linearly polarized attosecond extreme ultraviolet pulses. When the molecules are aligned perpendicular to laser polarization direction, photonionization of these molecules show clear and distinguishing diffraction patterns in molecular attosecond photoelectron momentum distributions. The internuclear distances of the molecules are related to the position of the associated diffraction patterns, which can be determined with high accuracy. Moreover, the relative heights of the diffraction fringes contain fruitful information of the molecular orbital structures. We show that the diffraction spectra can be well produced using the two-center interference model. By adopting a simple inversion algorithm which takes into account the symmetry of the initial molecular orbital, we can retrieve the molecular orbital from which the electron is ionized. Our results offer possibility for imaging of molecular structure and orbitals by performing molecular attosecond photoelectron diffraction.

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

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

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

  4. Monolithic integration of microelectronics and photonics using molecularly engineered materials

    NASA Astrophysics Data System (ADS)

    Kubacki, Ronald M.

    2005-03-01

    The monolithic integration of CMOS microelectronics with photonics is inevitable and benefits both technologies. Photonic integration to microelectronics provides such solutions as overcoming microprocessor communication roadblocks through the use of optical interconnection. Microelectronic integration can provide benefits to photonic structures by optimizing electronic signals generated by photonic biosensors for example. Photonic integration must complement, build on, and enhance the existing state of CMOS microelectronic technology. Photonic approaches that ignore the realities of CMOS architectures (such as power and thermal limitations), provide little benefit to the CMOS device performance, are incompatible with CMOS silicon manufacturing processes, or are incapable of achieving levels of long term reliability already well demonstrated by microelectronic devices, give little reason for photonic/microelectronic integration. Practical implementation of photonics on chip, monolithically with CMOS type microelectronic devices, remains in the laboratory. This work presents architectures to integrate photonics and microelectronics that address CMOS fabrication realities, increase performance of both the electronic and optical functions, and retain current levels of reliability. Fabricating these structures with the limited CMOS material set and/or typical photonic materials requires materials to be molecularly engineered to provide required properties. Materials have been investigated that enable economic fabrication of photonic structures for monolithic integration. Low loss self assembled silicon nanocomposite VIPIR waveguide structures are combined with long term stable non-linear poled polymers for fabrication of electro-optic active devices. Materials are fabricated using low temperature plasma enhanced chemical vapor deposition (PECVD).

  5. 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.

  6. 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.

  7. Molecular imaging probes spy on the body's inner workings: miniaturized microscopes, microbubbles, 7- and 15-T scanners, diffusion-tensor MRI, and other molecular-imaging technologies are pushing molecular imaging into the future.

    PubMed

    Mertz, Leslie

    2013-01-01

    Molecular imaging is one of the hot-button areas within medical imaging. This technology employs imaging techniques in concert with molecular probes, or biomarkers, that together noninvasively spy on cellular function and molecular processes. In some cases, this technology may be able to detect the very earliest stages of diseases and eliminate them on the spot. This paper discusses how miniaturized microscopes, microbubbles, 7T and 15T scanners, diffusion-tensor MRI and other molecular imaging technologies are pushing molecular imaging into the future.

  8. 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

  9. 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.

  10. Noninvasive structural, functional, and molecular imaging in drug development.

    PubMed

    Rudin, Markus

    2009-06-01

    Modern drug research is mechanism-based and the development of disease modifying therapies involves the identification of molecular key players in the pathological cascade. Today, noninvasive imaging tools enable the visualization and quantitative assessment of the expression of molecular targets, of their interaction with potential ligands, as well as of the functional consequence of this interaction at a molecular (e.g. activation of signaling cascades), cellular, metabolic, physiological, and morphological level in a temporo-spatially resolved manner. The ability to gather such information from the intact organism with all regulatory processes in place renders imaging highly attractive for the biomedical researcher and for the drug developer in particular. Molecular imaging is potentially capable of providing this information. Today, proof-of-principle has been established that imaging is in fact adding value to the drug discovery and development processes. Numerous studies have used structural and functional imaging readouts to document therapy efficacy, mainly during lead optimization. Similarly, major efforts have been devoted to the development and evaluation of imaging biomarkers that might serve as early readouts for therapy response with the potential of being used in the clinical drug evaluation thereby facilitating translational research. In this contribution, we illustrate the role and potential of imaging in modern drug discovery and development with selected examples. Yet, despite its huge potential the impact of imaging on drug discovery has been modest in the past; potential reasons will be discussed. Nevertheless, noninvasive imaging methods are rapidly evolving and it is beyond doubt that their importance for biomedical research will increase.

  11. Resolution-enhancement for an orthographic-view image display in an integral imaging microscope system

    PubMed Central

    Kwon, Ki-Chul; Jeong, Ji-Seong; Erdenebat, Munkh-Uchral; Piao, Yan-Ling; Yoo, Kwan-Hee; Kim, Nam

    2015-01-01

    Due to the limitations of micro lens arrays and camera sensors, images on display devices through the integral imaging microscope systems have been suffering for a low-resolution. In this paper, a resolution-enhanced orthographic-view image display method for integral imaging microscopy is proposed and demonstrated. Iterative intermediate-view reconstructions are performed based on bilinear interpolation using neighborhood elemental image information, and a graphics processing unit parallel processing algorithm is applied for fast image processing. The proposed method is verified experimentally and the effective results are presented in this paper. PMID:25798299

  12. Advances in molecular imaging for breast cancer detection and characterization

    PubMed Central

    2012-01-01

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

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

    PubMed

    Mahajan, A; Goh, V; Basu, S; Vaish, R; Weeks, A J; Thakur, M H; Cook, G J

    2015-10-01

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

  14. 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.

  15. 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.

  16. An Integrity Framework for Image-Based Navigation Systems

    DTIC Science & Technology

    2010-06-01

    AN INTEGRITY FRAMEWORK FOR IMAGE-BASED NAVIGATION SYSTEMS DISSERTATION Craig D. Larson, Captain, USAF AFIT/DEE/ENG/ 10 -03 DEPARTMENT OF THE AIR FORCE...United States AFIT/DEE/ENG/ 10 -03 AN INTEGRITY FRAMEWORK FOR IMAGE-BASED NAVIGATION SYSTEMS DISSERTATION Presented to the Faculty Graduate School of...UNLIMITED AFIT/DEE/ENG/ 10 -03 Abstract The value of Global Navigation Satellite Systems (GNSS) in a multitude of both military and civilian navigation and

  17. Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

    PubMed Central

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

    2015-01-01

    Summary 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

  18. Molecular imaging of brain tumors personal experience and review of the literature.

    PubMed

    Schaller, Bernhard J; Cornelius, Jan F; Sandu, Nora; Buchfelder, Michael

    2008-12-01

    HSV-1-TK expression if the blood brain barrier is disrupted. The higher uptake of [(18)F]FLT in the wild-type compared to the transduced type may demonstrate the different doubling time of both tumor tissues suggesting different cytosolic thymidine kinase activity. Molecular imaging probes are developed to image the function of targets without disturbing them or as drug in oder to modify the target's function. This is transfer of gene therapy's experimental knowledge into clinical applications. Molecular imaging closes the gap between in vitro to in vivo integrative biology of disease.

  19. Molecular imaging of cell-mediated cancer immunotherapy.

    PubMed

    Lucignani, Giovanni; Ottobrini, Luisa; Martelli, Cristina; Rescigno, Maria; Clerici, Mario

    2006-09-01

    New strategies based on the activation of a patient's immune response are being sought to complement present conventional exogenous cancer therapies. Elucidating the trafficking pathways of immune cells in vivo, together with their migratory properties in relation to their differentiation and activation status, is useful for understanding how the immune system interacts with cancer. Methods based on tissue sampling to monitor immune responses are inadequate for repeatedly characterizing the responses of the immune system in different organs. A solution to this problem might come from molecular and cellular imaging - a branch of biomedical sciences that combines biotechnology and imaging methods to characterize, in vivo, the molecular and cellular processes involved in normal and pathologic states. The general concepts of noninvasive imaging of targeted cells as well as the technology and probes applied to cell-mediated cancer immunotherapy imaging are outlined in this review.

  20. Recent advances in molecular, multimodal and theranostic ultrasound imaging.

    PubMed

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

    2014-06-01

    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 MBs 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.

  1. 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.

  2. 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

  3. Integration of multimodality images: success and future directions

    NASA Astrophysics Data System (ADS)

    Chen, Chin-Tu

    1993-07-01

    The concept of multi-modality image integration, in which images obtained from different sensors are co-registered spatially and various aspects of object characteristics revealed by individual imaging techniques are synergistically fused in order to yield new information, has received considerable attention in recent years. The initial success was made in visualizing integrated brain images which show the overlay of physiological information from PET or SPECT with anatomical information from CT or MRI, providing new knowledge of correlates of brain function and brain structure that was difficult to access previously. Extension of this concept to cardiac and pulmonary imaging is still in its infancy. One additional difficulty in dealing with cardiac/pulmonary data sets is the issue of motion. However, some features in periodic motion may offer additional information for the purpose of spatial co-registration. In addition to visualization of the fused image data in 2-D and 3-D, future directions in the arena of image integration from multiple modalities include multi-modal image reconstruction, multi-modal image segmentation and feature extraction, and other image analysis tasks that incorporate information available from multiple sources.

  4. An integrated compact airborne multispectral imaging system using embedded computer

    NASA Astrophysics Data System (ADS)

    Zhang, Yuedong; Wang, Li; Zhang, Xuguo

    2015-08-01

    An integrated compact airborne multispectral imaging system using embedded computer based control system was developed for small aircraft multispectral imaging application. The multispectral imaging system integrates CMOS camera, filter wheel with eight filters, two-axis stabilized platform, miniature POS (position and orientation system) and embedded computer. The embedded computer has excellent universality and expansibility, and has advantages in volume and weight for airborne platform, so it can meet the requirements of control system of the integrated airborne multispectral imaging system. The embedded computer controls the camera parameters setting, filter wheel and stabilized platform working, image and POS data acquisition, and stores the image and data. The airborne multispectral imaging system can connect peripheral device use the ports of the embedded computer, so the system operation and the stored image data management are easy. This airborne multispectral imaging system has advantages of small volume, multi-function, and good expansibility. The imaging experiment results show that this system has potential for multispectral remote sensing in applications such as resource investigation and environmental monitoring.

  5. 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.

  6. 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.

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

    PubMed Central

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

    2016-01-01

    Background MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). Methods One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Results Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. Conclusions By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. PMID:26188015

  8. 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.

  9. 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.

  10. 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.

  11. Integrated intravascular optical coherence tomography ultrasound imaging system.

    PubMed

    Yin, Jiechen; Yang, Hao-Chung; Li, Xiang; Zhang, Jun; Zhou, Qifa; Hu, Changhong; Shung, K Kirk; Chen, Zhongping

    2010-01-01

    We report on a dual-modality optical coherence tomography (OCT) ultrasound (US) system for intravascular imaging. To the best of our knowledge, we have developed the first integrated OCT-US probe that combines OCT optical components with an US transducer. The OCT optical components mainly consist of a single-mode fiber, a gradient index lens for light-beam focusing, and a right-angled prism for reflecting light into biological tissue. A 40-MHz piezoelectric transducer (PZT-5H) side-viewing US transducer was fabricated to obtain the US image. These components were integrated into a single probe, enabling both OCT and US imaging at the same time. In vitro OCT and ultrasound images of a rabbit aorta were obtained using this dual-modality imaging system. This study demonstrates the feasibility of an OCT-US system for intravascular imaging, which is expected to have a prominent impact on early detection and characterization of atherosclerosis.

  12. Integrated intravascular optical coherence tomography ultrasound imaging system

    PubMed Central

    Yin, Jiechen; Yang, Hao-Chung; Li, Xiang; Zhang, Jun; Zhou, Qifa; Hu, Changhong; Shung, K. Kirk; Chen, Zhongping

    2010-01-01

    We report on a dual-modality optical coherence tomography (OCT) ultrasound (US) system for intravascular imaging. To the best of our knowledge, we have developed the first integrated OCT-US probe that combines OCT optical components with an US transducer. The OCT optical components mainly consist of a single-mode fiber, a gradient index lens for light-beam focusing, and a right-angled prism for reflecting light into biological tissue. A 40-MHz piezoelectric transducer (PZT-5H) side-viewing US transducer was fabricated to obtain the US image. These components were integrated into a single probe, enabling both OCT and US imaging at the same time. In vitro OCT and ultrasound images of a rabbit aorta were obtained using this dual-modality imaging system. This study demonstrates the feasibility of an OCT-US system for intravascular imaging, which is expected to have a prominent impact on early detection and characterization of atherosclerosis. PMID:20210424

  13. [Consistent presentation of medical images based on CPI integration profile].

    PubMed

    Jiang, Tao; An, Ji-ye; Chen, Zhong-yong; Lu, Xu-dong; Duan, Hui-long

    2007-11-01

    Because of different display parameters and other factors, digital medical images present different display states in different section offices of a hospital. Based on CPI integration profile of IHE, this paper implements the consistent presentation of medical images, and it is helpful for doctors to carry out medical treatments of teamwork.

  14. An integral design strategy combining optical system and image processing to obtain high resolution images

    NASA Astrophysics Data System (ADS)

    Wang, Jiaoyang; Wang, Lin; Yang, Ying; Gong, Rui; Shao, Xiaopeng; Liang, Chao; Xu, Jun

    2016-05-01

    In this paper, an integral design that combines optical system with image processing is introduced to obtain high resolution images, and the performance is evaluated and demonstrated. Traditional imaging methods often separate the two technical procedures of optical system design and imaging processing, resulting in the failures in efficient cooperation between the optical and digital elements. Therefore, an innovative approach is presented to combine the merit function during optical design together with the constraint conditions of image processing algorithms. Specifically, an optical imaging system with low resolution is designed to collect the image signals which are indispensable for imaging processing, while the ultimate goal is to obtain high resolution images from the final system. In order to optimize the global performance, the optimization function of ZEMAX software is utilized and the number of optimization cycles is controlled. Then Wiener filter algorithm is adopted to process the image simulation and mean squared error (MSE) is taken as evaluation criterion. The results show that, although the optical figures of merit for the optical imaging systems is not the best, it can provide image signals that are more suitable for image processing. In conclusion. The integral design of optical system and image processing can search out the overall optimal solution which is missed by the traditional design methods. Especially, when designing some complex optical system, this integral design strategy has obvious advantages to simplify structure and reduce cost, as well as to gain high resolution images simultaneously, which has a promising perspective of industrial application.

  15. Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers.

    PubMed

    Strafella, Antonio P; Bohnen, Nicolaas I; Perlmutter, Joel S; Eidelberg, David; Pavese, Nicola; Van Eimeren, Thilo; Piccini, Paola; Politis, Marios; Thobois, Stephane; Ceravolo, Roberto; Higuchi, Makoto; Kaasinen, Valtteri; Masellis, Mario; Peralta, M Cecilia; Obeso, Ignacio; Pineda-Pardo, Jose Ángel; Cilia, Roberto; Ballanger, Benedicte; Niethammer, Martin; Stoessl, Jon A

    2017-02-01

    Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society.

  16. 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.

  17. Coupling molecular spin centers to microwave planar resonators: towards integration of molecular qubits in quantum circuits.

    PubMed

    Bonizzoni, C; Ghirri, A; Bader, K; van Slageren, J; Perfetti, M; Sorace, L; Lan, Y; Fuhr, O; Ruben, M; Affronte, M

    2016-11-14

    We present spectroscopic measurements looking for the coherent coupling between molecular magnetic centers and microwave photons. The aim is to find the optimal conditions and the best molecular features to achieve the quantum strong coupling regime, for which coherent dynamics of hybrid photon-spin states take place. To this end, we used a high critical temperature YBCO superconducting planar resonator working at 7.7 GHz and at low temperatures to investigate three molecular mononuclear coordination compounds, namely (PPh4)2[Cu(mnt)2] (where mnt(2-) = maleonitriledithiolate), [ErPc2](-)TBA(+) (where pc(2-) is the phtalocyaninato and TBA(+) is the tetra-n-butylammonium cation) and Dy(trensal) (where H3trensal = 2,2',2''-tris(salicylideneimino)triethylamine). Although the strong coupling regime was not achieved in these preliminary experiments, the results provided several hints on how to design molecular magnetic centers to be integrated into hybrid quantum circuits.

  18. 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.

  19. Molecular Imaging and Contrast Agent Database (MICAD): evolution and progress.

    PubMed

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

    2012-02-01

    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 >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values 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, pre-clinical 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.

  20. Molecular imaging and the unification of multilevel mechanisms and data in medical physics.

    PubMed

    Nikiforidis, George C; Sakellaropoulos, George C; Kagadis, George C

    2008-08-01

    Molecular imaging (MI) constitutes a recently developed approach of imaging, where modalities and agents have been reinvented and used in novel combinations in order to expose and measure biologic processes occurring at molecular and cellular levels. It is an approach that bridges the gap between modalities acquiring data from high (e.g., computed tomography, magnetic resonance imaging, and positron-emitting isotopes) and low (e.g., PCR, microarrays) levels of a biological organization. While data integration methodologies will lead to improved diagnostic and prognostic performance, interdisciplinary collaboration, triggered by MI, will result in a better perception of the underlying biological mechanisms. Toward the development of a unifying theory describing these mechanisms, medical physicists can formulate new hypotheses, provide the physical constraints bounding them, and consequently design appropriate experiments. Their new scientific and working environment calls for interventions in their syllabi to educate scientists with enhanced capabilities for holistic views and synthesis.

  1. Improved microgrid arrangement for integrated imaging polarimeters.

    PubMed

    LeMaster, Daniel A; Hirakawa, Keigo

    2014-04-01

    For almost 20 years, microgrid polarimetric imaging systems have been built using a 2×2 repeating pattern of polarization analyzers. In this Letter, we show that superior spatial resolution is achieved over this 2×2 case when the analyzers are arranged in a 2×4 repeating pattern. This unconventional result, in which a more distributed sampling pattern results in finer spatial resolution, is also achieved without affecting the conditioning of the polarimetric data-reduction matrix. Proof is provided theoretically and through Stokes image reconstruction of synthesized data.

  2. 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.

  3. Recent Advances of Radionuclide-based Molecular Imaging of Atherosclerosis

    PubMed Central

    Kazuma, Soraya M.; Sultan, Deborah; Zhao, Yongfeng; Detering, Lisa; You, Meng; Luehmann, Hannah P.; Abdalla, Dulcineia S.P.; Liu, Yongjian

    2015-01-01

    Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclide-based imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression. PMID:26369676

  4. 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

  5. Integrating digital topology in image-processing libraries.

    PubMed

    Lamy, Julien

    2007-01-01

    This paper describes a method to integrate digital topology informations in image-processing libraries. This additional information allows a library user to write algorithms respecting topological constraints, for example, a seed fill or a skeletonization algorithm. As digital topology is absent from most image-processing libraries, such constraints cannot be fulfilled. We describe and give code samples for all the structures necessary for this integration, and show a use case in the form of a homotopic thinning filter inside ITK. The obtained filter can be up to a hundred times as fast as ITK's thinning filter and works for any image dimension. This paper mainly deals of integration within ITK, but can be adapted with only minor modifications to other image-processing libraries.

  6. Molecular subtypes and imaging phenotypes of breast cancer

    PubMed Central

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics. PMID:27599892

  7. Silver Nanoplate Contrast Agents for In Vivo Molecular Photoacoustic Imaging

    PubMed Central

    Homan, Kimberly A.; Souza, Michael; Truby, Ryan; Luke, Geoffrey P.; Green, Christopher; Vreeland, Erika; Emelianov, Stanislav

    2012-01-01

    Silver nanoplates are introduced as a new photoacoustic contrast agent that can be easily functionalized for molecular photoacoustic imaging in vivo. Methods are described for synthesis, functionalization, and stabilization of silver nanoplates using biocompatible (“green”) reagents. Directional antibody conjugation to the nanoplate surface is presented along with proof of molecular sensitivity in vitro with pancreatic cancer cells. Cell viability tests show the antibody-conjugated silver nanoplates to be nontoxic at concentrations up to 1 mg/ml. Furthermore, the silver nanoplates' potential for in vivo application as a molecularly sensitive photoacoustic contrast agent is demonstrated using an orthotopic mouse model of pancreatic cancer. Results of these studies suggest that the synthesized silver nanoplates are well suited for a host of biomedical imaging and sensing applications. PMID:22188516

  8. Aptamers Selected by Cell-SELEX for Molecular Imaging.

    PubMed

    Jin, Cheng; Zheng, Jing; Li, Chunmei; Qiu, Liping; Zhang, Xiaobing; Tan, Weihong

    2015-12-01

    Conventional diagnostics for cancer rely primarily on anatomical techniques. However, these techniques cannot monitor the changes at the molecular level in normal cells, which possibly signal the onset of cancer at its very earliest stages. For accurate prediction of the carcinogenesis at the molecular level, targeting ligands have been used in combination with imaging probes to monitor this biological process. Among these targeting ligands, aptamers have high binding affinity to various targets ranging from small molecules to whole organisms, and, hence, exceptional recognition ability. Many recent studies have been reported on aptamer-based molecular imaging, clearly indicating its clinical and diagnostic utility. In this review, we will discuss some key results of these studies.

  9. Practical Methods for Molecular In Vivo Optical Imaging.

    PubMed

    Chen, Hannah; Thorne, Stephen H

    2012-01-01

    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.

  10. 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

  11. Inverse transport problems in quantitative PAT for molecular imaging

    NASA Astrophysics Data System (ADS)

    Ren, Kui; Zhang, Rongting; Zhong, Yimin

    2015-12-01

    Fluorescence photoacoustic tomography (fPAT) is a molecular imaging modality that combines photoacoustic tomography with fluorescence imaging to obtain high-resolution imaging of fluorescence distributions inside heterogeneous media. The objective of this work is to study inverse problems in the quantitative step of fPAT where we intend to reconstruct physical coefficients in a coupled system of radiative transport equations using internal data recovered from ultrasound measurements. We derive uniqueness and stability results on the inverse problems and develop some efficient algorithms for image reconstructions. Numerical simulations based on synthetic data are presented to validate the theoretical analysis. The results we present here complement these in Ren K and Zhao H (2013 SIAM J. Imaging Sci. 6 2024-49) on the same problem but in the diffusive regime.

  12. 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

  13. 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

  14. Myocardial Ischemic Memory Imaging With Molecular Echocardiography

    PubMed Central

    Villanueva, Flordeliza S.; Lu, Erxiong; Bowry, Shivani; Kilic, Sevgi; Tom, Eric; Wang, Jianjun; Gretton, Joan; Pacella, John J.; Wagner, William R.

    2014-01-01

    Background Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium. Methods and Results Lipid microbubbles (diameter, 3.3±1.7 μm) were synthesized. The selectin ligand sialyl Lewisx was conjugated to the microbubble surface (MBsLex). Control bubbles (MBCTL) bore surface Lewisx or sialyl Lewisc. Intravital microscopy of mouse cremaster muscle was performed after intravenous injection of MBsLex (n=11) or MBCTL (n=9) with or without prior intrascrotal tumor necrosis factor–α. There was greater adhesion of MBsLex to inflamed versus noninflamed endothelium (P=0.0081). Rats (n=12) underwent 15 minutes of anterior descending coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high-mechanical-index nonlinear echocardiographic imaging was performed in which single frames were acquired at 3.5 and 4 minutes after intravenous injection of MBsLex or MBCTL. Video intensity at 4 minutes was subtracted from that at 3.5 minutes to derive target-specific acoustic signal. MBsLex caused greater opacification in postischemic versus nonischemic myocardium at both time points (P≤0.002). Immunostaining confirmed endothelial P-selectin expression in the ischemic bed. Conclusions Echocardiographic identification of recently ischemic myocardium is possible using ultrasound contrast agents targeted to selectins. This may offer a new approach to the more timely and precise diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain cardiac origin. PMID:17210843

  15. 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

  16. Integrative network analysis reveals molecular mechanisms of blood pressure regulation

    PubMed Central

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension. PMID:25882670

  17. Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction

    NASA Astrophysics Data System (ADS)

    Freyer, Marcus; Ale, Angelique; Schulz, Ralf B.; Zientkowska, Marta; Ntziachristos, Vasilis; Englmeier, Karl-Hans

    2010-05-01

    The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

  18. Changing paradigms with molecular imaging of neuroendocrine tumors.

    PubMed

    Hofman, Michael S; Hicks, Rodney J

    2012-07-01

    Molecular imaging is changing diagnostic and treatment paradigms in patients with neuroendocrine tumors through its ability to non-invasively characterize disease, supplementing the traditional role of using imaging for localizing and measuring disease. For patients with metastatic disease, there is an increasing range of therapies but these must be individualized to the specific subtype of tumor expressed, which varies in aggressiveness from well to poorly differentiated phenotypes. Positron emission tomography (PET) is now able to characterize these subtypes through its ability to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism with SSTR and fluorodeoxyglucose (FDG) PET, respectively. The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. Through earlier diagnosis, improved selection of the most appropriate therapy and better assessment of therapeutic response for an individual patient, molecular imaging is improving the outcome for patients with NET.

  19. Molecular, Functional, and Structural Imaging of Major Depressive Disorder.

    PubMed

    Zhang, Kai; Zhu, Yunqi; Zhu, Yuankai; Wu, Shuang; Liu, Hao; Zhang, Wei; Xu, Caiyun; Zhang, Hong; Hayashi, Takuya; Tian, Mei

    2016-06-01

    Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

  20. Molecular pathology - the value of an integrative approach.

    PubMed

    Salto-Tellez, Manuel; James, Jacqueline A; Hamilton, Peter W

    2014-10-01

    Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall. Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know-how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high-quality for biomarker discovery, biomarker validation and molecular diagnostics.

  1. 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.

  2. Path integral molecular dynamics at zero thermal temperature

    NASA Astrophysics Data System (ADS)

    Willow, Soohaeng Yoo

    2017-04-01

    Path integral molecular dynamics (PIMD) simulations at the zero thermal temperature still remain inconceivable. Herein, the quantum-mechanical partition function is revised in conjunction with the time-independent Schrödinger equation. The imaginary temperature for the quantum-mechanical partition function is introduced as an independent variable and defined under the guidance of the virial theorem. In the end, computational evidences are provided showing that this revised PIMD simulation at the zero thermal temperature reproduces both the zero-point energy and the probability density obtained from the Schrödinger equation for the harmonic oscillator.

  3. 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

  4. In vivo Cerenkov luminescence imaging: a new tool for molecular imaging.

    PubMed

    Mitchell, Gregory S; Gill, Ruby K; Boucher, David L; Li, Changqing; Cherry, Simon R

    2011-11-28

    Cerenkov radiation is a phenomenon where optical photons are emitted when a charged particle moves faster than the speed of light for the medium in which it travels. Recently, we and others have discovered that measurable visible light due to the Cerenkov effect is produced in vivo following the administration of β-emitting radionuclides to small animals. Furthermore, the amounts of injected activity required to produce a detectable signal are consistent with small-animal molecular imaging applications. This surprising observation has led to the development of a new hybrid molecular imaging modality known as Cerenkov luminescence imaging (CLI), which allows the spatial distribution of biomolecules labelled with β-emitting radionuclides to be imaged in vivo using sensitive charge-coupled device cameras. We review the physics of Cerenkov radiation as it relates to molecular imaging, present simulation results for light intensity and spatial distribution, and show an example of CLI in a mouse cancer model. CLI allows many common radiotracers to be imaged in widely available in vivo optical imaging systems, and, more importantly, provides a pathway for directly imaging β(-)-emitting radionuclides that are being developed for therapeutic applications in cancer and that are not readily imaged by existing methods.

  5. Towards an integrated molecular model of plant-virus interactions.

    PubMed

    Elena, Santiago F; Rodrigo, Guillermo

    2012-12-01

    The application in recent years of network theory methods to the study of host-virus interactions is providing a new perspective to the way viruses manipulate the host to promote their own replication. An integrated molecular model of such pathosystems require three detailed maps describing, firstly, the interactions between viral elements, secondly, the interactions between host elements, and thirdly, the cross-interactions between viral and host elements. Here, we compile available information for Potyvirus infecting Arabidopsis thaliana. With an integrated model, it is possible to analyze the mode of virus action and how the perturbation of the virus targets propagates along the network. These studies suggest that viral pathogenicity results not only from the alteration of individual elements but it is a systemic property.

  6. Integrated microsystems for optical sensing and imaging applications

    NASA Astrophysics Data System (ADS)

    Kleindienst, Roman; Sinzinger, Stefan

    2016-03-01

    Compact optical systems generally form the backbone of integrated optoelectronic microsystems. Miniaturization as well as integration requirements result in system configurations with folded optical axis such as in planar integrated freespace optics. For optimum performance in such systems geometries, the surface profiles of the corresponding optical elements deviate from classical spherical or aspherical shapes. Optimized plane-symmetric or freeform optical elements are required instead. We discuss design, fabrication and characterization of freeform optical elements for the integration of optical microsystems. The systems performance is demonstrated for imaging as well as sensor applications.

  7. A unified scheme for ab initio molecular orbital theory and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Tachikawa, Masanori; Miura, Shinichi

    2001-11-01

    We present a general approach for accurate calculation of chemical substances which treats both nuclei and electrons quantum mechanically, adopting ab initio molecular orbital theory for the electronic structure and path integral molecular dynamics for the nuclei. The present approach enables the evaluation of physical quantities dependent on the nuclear configuration as well as the electronic structure, within the framework of Born-Oppenheimer adiabatic approximation. As an application, we give the path integral formulation of electric response properties—dipole moment and polarizability, which characterize the changes both in electronic structure and nuclear configuration at a given temperature when uniform electrostatic field is present. We also demonstrate the calculation of a water molecule using the present approach and the result of temperature and isotope effects is discussed.

  8. 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

  9. 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.

  10. 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.

  11. Encrypting 2D/3D image using improved lensless integral imaging in Fresnel domain

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Wei; Wang, Qiong-Hua; Kim, Seok-Tae; Lee, In-Kwon

    2016-12-01

    We propose a new image encryption technique, for the first time to our knowledge, combined Fresnel transform with the improved lensless integral imaging technique. In this work, before image encryption, the input image is first recorded into an elemental image array (EIA) by using the improved lensless integral imaging technique. The recorded EIA is encrypted into random noise by use of two phase masks located in the Fresnel domain. The positions of phase masks and operation wavelength, as well as the integral imaging system parameters are used as encryption keys that can ensure security. Compared with previous works, the main novelty of this proposed method resides in the fact that the elemental images possess distributed memory characteristic, which greatly improved the robustness of the image encryption algorithm. Meanwhile, the proposed pixel averaging algorithm can effectively address the overlapping problem existing in the computational integral imaging reconstruction process. Numerical simulations are presented to demonstrate the feasibility and effectiveness of the proposed method. Results also indicate the high robustness against data loss attacks.

  12. Integrated genomic and molecular characterization of cervical cancer.

    PubMed

    2017-03-16

    Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

  13. Contrast ultrasound molecular imaging of inflammation in cardiovascular disease.

    PubMed

    Lindner, Jonathan R

    2009-11-01

    The cellular immune response plays an important role in almost every major form of cardiovascular disease. The ability to image the key aspects of the immune response in the clinical setting could be used to improve diagnostic information, to provide important prognostic or risk information, and to customize therapy according to disease phenotype. Accordingly, targeted imaging probes for assessing inflammation have been developed for essentially all forms of medical imaging. Molecular imaging of inflammation with contrast ultrasound relies on the detection of targeted microbubble or other gas-filled particle contrast agents. These agents are confined to the vascular space and, hence, have been targeted to either activated leucocytes or endothelial cell adhesion molecules that are upregulated in inflammation and mediate leucocyte recruitment and adhesion. This review focuses on the inflammation-targeting strategies for ultrasound contrast agents and how they have been matched to cardiovascular disease states such as myocardial ischaemia, infarction, atherosclerosis, transplant rejection, and arteriogenesis.

  14. Integrated bio-inspired fluidic imaging system

    NASA Astrophysics Data System (ADS)

    Tsai, Frank S.; Johnson, Daniel; Cho, Sung Hwan; Qiao, Wen; Arianpour, Ashkan; Francis, Cameron S.; Kim, Nam-Hyong; Lo, Yu-Hwa

    2010-02-01

    We developed a new type of optical lens device that can change its curvature like crystalline lens in human eye. The curvature changing capability of the lens allows for a tremendous tuning range in its optical power and subsequently enables miniaturized imaging systems that can perform autofocus, optical zoom, and other advanced functions. In this paper, we study the physical properties of bio-inspired fluidic lenses and demonstrate the optical functionality through miniaturized optical systems constructed with such lenses. We report an auto-focusing optical system that can turn from a camera to a microscope, and demonstrate more than 4X optical zoom with a very short total track length. Finally, we demonstrate the benefits of fluidic lens zoom camera through minimally invasive gallbladder removal surgery.

  15. Orthoscopic real image reconstruction in integral imaging by rotating an elemental image based on the reference point of object space.

    PubMed

    Jang, Jae-Young; Cho, Myungjin

    2015-06-20

    We propose a new approach for depth conversion of three-dimensional (3D) reconstruction from pseudoscopic to orthoscopic real images in resolution priority integral imaging. In integral imaging, depth of field is recorded in an elemental image array. In the proposed method, the depth information is converted by a 180° rotation of each elemental image in an elemental image array based on a reference point of conversion, which is caused by a reference point of object space. Orthoscopic real images can be reconstructed in 3D space by using the depth conversion of an elemental image array. The feasibility of the proposed method has been confirmed through preliminary experiments as well as ray optical analysis.

  16. Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation

    PubMed Central

    Abou, D S; Pickett, J E

    2015-01-01

    Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed. PMID:26133075

  17. Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry.

    PubMed

    Li, Yue; Shrestha, Bindesh; Vertes, Akos

    2007-01-15

    An atmospheric pressure (AP) MALDI imaging interface was developed for an orthogonal acceleration time-of-flight mass spectrometer and utilized to analyze peptides, carbohydrates, and other small biomolecules using infrared laser excitation. In molecular imaging experiments, the spatial distribution of mock peptide patterns was recovered with a detection limit of approximately 1 fmol/pixel from a variety of MALDI matrixes. With the use of oversampling for the image acquisition, a spatial resolution of 40 microm, 5 times smaller than the laser spot size, was achieved. This approach, however, required that the analyte was largely removed at the point of analysis before the next point was interrogated. Native water in plant tissue was demonstrated to be an efficient natural matrix for AP infrared laser desorption ionization. In soft fruit tissues from bananas, grapes, and strawberries, potassiated ions of the most abundant metabolites, small carbohydrates, and their clusters produced the strongest peaks in the spectra. Molecular imaging of a strawberry skin sample revealed the distribution of the sucrose, glucose/fructose, and citric acid species around the embedded seeds. Infrared AP MALDI mass spectrometric imaging without the addition of an artificial matrix enables the in vivo investigation of small biomolecules and biological processes (e.g., metabolomics) in their natural environment.

  18. 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.

  19. 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.

  20. Fluorescent Molecular Tomography for In Vivo Imaging of Mouse Atherosclerosis.

    PubMed

    Arranz, Alicia; Rudin, Markus; Zaragoza, Carlos; Ripoll, Jorge

    2015-01-01

    Optical imaging technologies such as fluorescence molecular tomography (FMT) are gaining great relevance in cardiovascular research. The main reason is the increased number of available fluorescent agents, especially those termed "activatable probes," which remain quenched under baseline conditions and are fluorescent when a specific enzymatic activity is present. A major characteristic of FMT is the possibility of obtaining quantitative data of fluorescence signal distribution in a noninvasive fashion and using nonionizing radiation, making FMT an invaluable tool for longitudinal studies with biomedical applications. Here, we describe a standard procedure to perform FMT experiments in atherosclerosis mouse models, from the handling of the animals to the reconstruction of the 3D images.

  1. Kinetic modeling based probabilistic segmentation for molecular images.

    PubMed

    Saad, Ahmed; Hamarneh, Ghassan; Möller, Torsten; Smith, Ben

    2008-01-01

    We propose a semi-supervised, kinetic modeling based segmentation technique for molecular imaging applications. It is an iterative, self-learning algorithm based on uncertainty principles, designed to alleviate low signal-to-noise ratio (SNR) and partial volume effect (PVE) problems. Synthetic fluorodeoxyglucose (FDG) and simulated Raclopride dynamic positron emission tomography (dPET) brain images with excessive noise levels are used to validate our algorithm. We show, qualitatively and quantitatively, that our algorithm outperforms state-of-the-art techniques in identifying different functional regions and recovering the kinetic parameters.

  2. Molecular Imaging and Precision Medicine in Head and Neck Cancer.

    PubMed

    Mena, Esther; Thippsandra, Shwetha; Yanamadala, Anusha; Redy, Siddaling; Pattanayak, Puskar; Subramaniam, Rathan M

    2017-01-01

    The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms.

  3. 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

  4. Enhancing in vivo tumor boundary delineation with structured illumination fluorescence molecular imaging and spatial gradient mapping

    NASA Astrophysics Data System (ADS)

    Sun, Jessica; Miller, Jessica P.; Hathi, Deep; Zhou, Haiying; Achilefu, Samuel; Shokeen, Monica; Akers, Walter J.

    2016-08-01

    Fluorescence imaging, in combination with tumor-avid near-infrared (NIR) fluorescent molecular probes, provides high specificity and sensitivity for cancer detection in preclinical animal models, and more recently, assistance during oncologic surgery. However, conventional camera-based fluorescence imaging techniques are heavily surface-weighted such that surface reflection from skin or other nontumor tissue and nonspecific fluorescence signals dominate, obscuring true cancer-specific signals and blurring tumor boundaries. To address this challenge, we applied structured illumination fluorescence molecular imaging (SIFMI) in live animals for automated subtraction of nonspecific surface signals to better delineate accumulation of an NIR fluorescent probe targeting α4β1 integrin in mice bearing subcutaneous plasma cell xenografts. SIFMI demonstrated a fivefold improvement in tumor-to-background contrast when compared with other full-field fluorescence imaging methods and required significantly reduced scanning time compared with diffuse optical spectroscopy imaging. Furthermore, the spatial gradient mapping enhanced highlighting of tumor boundaries. Through the relatively simple hardware and software modifications described, SIFMI can be integrated with clinical fluorescence imaging systems, enhancing intraoperative tumor boundary delineation from the uninvolved tissue.

  5. 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.

  6. 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

  7. Free segmentation in rendered 3D images through synthetic impulse response in integral imaging

    NASA Astrophysics Data System (ADS)

    Martínez-Corral, M.; Llavador, A.; Sánchez-Ortiga, E.; Saavedra, G.; Javidi, B.

    2016-06-01

    Integral Imaging is a technique that has the capability of providing not only the spatial, but also the angular information of three-dimensional (3D) scenes. Some important applications are the 3D display and digital post-processing as for example, depth-reconstruction from integral images. In this contribution we propose a new reconstruction method that takes into account the integral image and a simplified version of the impulse response function (IRF) of the integral imaging (InI) system to perform a two-dimensional (2D) deconvolution. The IRF of an InI system has a periodic structure that depends directly on the axial position of the object. Considering different periods of the IRFs we recover by deconvolution the depth information of the 3D scene. An advantage of our method is that it is possible to obtain nonconventional reconstructions by considering alternative synthetic impulse responses. Our experiments show the feasibility of the proposed method.

  8. 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.

  9. Efficient stochastic thermostatting of path integral molecular dynamics.

    PubMed

    Ceriotti, Michele; Parrinello, Michele; Markland, Thomas E; Manolopoulos, David E

    2010-09-28

    The path integral molecular dynamics (PIMD) method provides a convenient way to compute the quantum mechanical structural and thermodynamic properties of condensed phase systems at the expense of introducing an additional set of high frequency normal modes on top of the physical vibrations of the system. Efficiently sampling such a wide range of frequencies provides a considerable thermostatting challenge. Here we introduce a simple stochastic path integral Langevin equation (PILE) thermostat which exploits an analytic knowledge of the free path integral normal mode frequencies. We also apply a recently developed colored noise thermostat based on a generalized Langevin equation (GLE), which automatically achieves a similar, frequency-optimized sampling. The sampling efficiencies of these thermostats are compared with that of the more conventional Nosé-Hoover chain (NHC) thermostat for a number of physically relevant properties of the liquid water and hydrogen-in-palladium systems. In nearly every case, the new PILE thermostat is found to perform just as well as the NHC thermostat while allowing for a computationally more efficient implementation. The GLE thermostat also proves to be very robust delivering a near-optimum sampling efficiency in all of the cases considered. We suspect that these simple stochastic thermostats will therefore find useful application in many future PIMD simulations.

  10. Efficient stochastic thermostatting of path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ceriotti, Michele; Parrinello, Michele; Markland, Thomas E.; Manolopoulos, David E.

    2010-09-01

    The path integral molecular dynamics (PIMD) method provides a convenient way to compute the quantum mechanical structural and thermodynamic properties of condensed phase systems at the expense of introducing an additional set of high frequency normal modes on top of the physical vibrations of the system. Efficiently sampling such a wide range of frequencies provides a considerable thermostatting challenge. Here we introduce a simple stochastic path integral Langevin equation (PILE) thermostat which exploits an analytic knowledge of the free path integral normal mode frequencies. We also apply a recently developed colored noise thermostat based on a generalized Langevin equation (GLE), which automatically achieves a similar, frequency-optimized sampling. The sampling efficiencies of these thermostats are compared with that of the more conventional Nosé-Hoover chain (NHC) thermostat for a number of physically relevant properties of the liquid water and hydrogen-in-palladium systems. In nearly every case, the new PILE thermostat is found to perform just as well as the NHC thermostat while allowing for a computationally more efficient implementation. The GLE thermostat also proves to be very robust delivering a near-optimum sampling efficiency in all of the cases considered. We suspect that these simple stochastic thermostats will therefore find useful application in many future PIMD simulations.

  11. Electrophoretic gel image analysis software for the molecular biology laboratory.

    PubMed

    Redman, T; Jacobs, T

    1991-06-01

    We present GelReader 1.0, a microcomputer program designed to make precision, digital analysis of one-dimensional electrophoretic gels accessible to the molecular biology laboratory of modest means. Images of electrophoretic gels are digitized via a desktop flatbed scanner from instant photographs, autoradiograms or chromogenically stained blotting media. GelReader is then invoked to locate lanes and bands and generate a report of molecular weights of unknowns, based on specified sets of standards. Frequently used standards can be stored in the program. Lanes and bands can be added or removed, based upon users' subjective preferences. A unique lane histogram feature facilitates precise manual addition of bands missed by the software. Image enhancement features include palette manipulation, histogram equalization, shadowing and magnification. The user interface strikes a balance between program autonomy and user intervention, in recognition of the variability in electrophoretic gel quality and users' analytical needs.

  12. Advances in molecular preclinical therapy mediated by imaging.

    PubMed

    Greco, Adelaide; Albanese, Sandra; Auletta, Luigi; DE Carlo, Flavia; Salvatore, Marco; Howard, Candace M; Claudio, Pier P

    2017-03-01

    Several advances have been made toward understanding the biology of cancer and most of them are due to robust genetic studies that led to the scientific recognition that although many patients have the same type of cancer their tumors may have harbored different molecular alterations. Personalized therapy and the development of advanced techniques of preclinical imaging and new murine models of disease are emerging concepts that are allowing mapping of disease markers in vivo and in some cases also receptor targeted therapy. Aim of this review is to illustrate some emerging models of disease that allow patient tumor implantation in mice for subsequent drug testing and advanced approaches for therapy mediated by preclinical imaging. In particular we discuss targeted therapy mediated by high frequency ultrasound and magnetic resonance, two emerging techniques in molecular preclinical therapy.

  13. FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

    PubMed Central

    Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

  14. Dynamic fluorescence imaging with molecular agents for cancer detection

    NASA Astrophysics Data System (ADS)

    Kwon, Sun Kuk

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

  15. NIR fluorescent ytterbium compound for in vivo fluorescence molecular imaging.

    PubMed

    Aita, Kazuki; Temma, Takashi; Kuge, Yuji; Seki, Koh-ichi; Saji, Hideo

    2010-01-01

    We have developed a new NIR fluorescent probe based on an ytterbium(III) (E)-1-(pyridin-2-yl-diazenyl)naphthalen-2-ol (PAN) complex. This probe emits near-infrared luminescence derived from the Yb ion through excitation of the PAN moiety with visible light (lambda(ex)= 530 nm, lambda(em)= 975 nm). The results support the possible utility of the probe for in vivo fluorescence molecular imaging.

  16. 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

  17. Ratiometric Photoacoustic Molecular Imaging for Methylmercury Detection in Living Subjects.

    PubMed

    Liu, Yi; Wang, Sheng; Ma, Ying; Lin, Jing; Wang, Hai-Yan; Gu, Yueqing; Chen, Xiaoyuan; Huang, Peng

    2017-02-22

    Photoacoustic molecular imaging is an emerging and promising diagnostic tool for heavy metal ions detection. Methylmercury (MeHg(+) ) is one of the most potent neurotoxins, which damages the brain and nervous system of human beings through fish consumption. The development of a selective and sensitive method for MeHg(+) detection is highly desirable. In this Communication, we develope a chemoselective photoacoustic sensor (LP-hCy7) composed of the liposome (LP) and MeHg(+) -responsive near-infrared (NIR) cyanine dye (hCy7) for MeHg(+) detection within living subjects, such as zebrafish and mouse. The as-prepared LP-hCy7 nanoprobe displays unique dual-shift NIR absorbance peaks and produces a normalized turn-on response after the reaction of MeHg(+) and hCy7 through a mercury-promoted cyclization reaction. The absorbance intensities of LP-hCy7 nanoprobe at 690 and 860 nm are decreased and increased, respectively. The ratiometric photoacoustic signal (PA860/PA690) is noticeably increased in the presence of MeHg(+) . These findings not only provide a ratiometric photoacoustic molecular imaging probe for the detection of metal ions in vivo, but also provides a tool for spectroscopic photoacoustic molecular imaging.

  18. Molecular Imaging in Tracking Tumor Stem-Like Cells

    PubMed Central

    Xia, Tian; Jiang, Han; Li, Chenrui; Tian, Mei; Zhang, Hong

    2012-01-01

    Cancer remains a major public health problem in many countries. It was found to contain a subset of cancer stem cells (CSCs) that are capable of proliferation and self-renewal, and differentiation into various types of cancer cells. CSCs often display characteristics of chemotherapy resistance and radiotherapy resistance. Numerous putative biomarkers of CSCs are currently identified including CD133, CD44, CD24, ALDH (aldehyde dehydrogenase), and ABCG2. Interestingly, no single marker is exclusively expressed by CSCs. Thus, the various combinations of different biomarkers will be possible to identify CSCs, and considerable work is being done to recognize new ones. In order to demonstrate the mechanisms of resistance and response to therapy and predict the outcome as well as prognosis, the ways to track and identify CSCs will be extremely important. The technologies of molecular imaging will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. Limited studies were investigated on the detection of various types of CSCs by molecular imaging. Although the tracking of circulating CSCs is still hampered by technological challenges, personalized diagnosis and therapies of cancers are expected to be established based on increased understanding of molecular imaging of cancer stem-like cells biomarkers. PMID:22570529

  19. Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease.

    PubMed

    Hirao, Kentaro; Pontone, Gregory M; Smith, Gwenn S

    2015-02-01

    Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome and/or a "risk factor" of neurodegenerative diseases. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer's disease (AD) and Parkinson's disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.

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

    PubMed

    Wachsmann, Jason; Peng, Fangyu

    2016-01-07

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

  1. 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

  2. Microwave Breast Imaging System Prototype with Integrated Numerical Characterization

    PubMed Central

    Haynes, Mark; Stang, John; Moghaddam, Mahta

    2012-01-01

    The increasing number of experimental microwave breast imaging systems and the need to properly model them have motivated our development of an integrated numerical characterization technique. We use Ansoft HFSS and a formalism we developed previously to numerically characterize an S-parameter- based breast imaging system and link it to an inverse scattering algorithm. We show successful reconstructions of simple test objects using synthetic and experimental data. We demonstrate the sensitivity of image reconstructions to knowledge of the background dielectric properties and show the limits of the current model. PMID:22481906

  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. Integrating Non-Semantic Knowledge into Image Segmentation Processes.

    DTIC Science & Technology

    1984-03-01

    D-A149 571 INTEGRATING NON-SEMANTIC KNOWLEDGE INTO IMAGE 1/2 SEGMENTATION PROCESSES(U) MRSSACHUSETTS UNIV AMHERST DEPT OF COMPUTER AND INFORMATION S... IMAGE SEGMENTATION PROCESSES Ralf R. Kohler COINS Technical Report 84-04 SJAN 1 7 1985) This work was supported in part by the Office of Naval Rearch...RR07048-16. DITPI~rN STTM!4 j~pwvq jx public 7le" Dwtnutlfl nlmited . .. Teatn Non-SanatIC Knowledge into Image Segmentation Proces A Dissertation

  5. 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

  6. 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.

  7. 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.

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

    SciTech Connect

    Roy, Nirupam; Momjian, Emmanuel; Datta, Abhirup; Sarma, Anuj P.

    2011-09-20

    Thioxoethenylidene (CCS) is an abundant interstellar molecule and a good tracer of high density and evolutionary stage of dense molecular clouds. It is also a suitable candidate for Zeeman splitting observations for its high splitting factor and narrow thermal line widths. We report here Expanded Very Large Array 22.3 GHz observations of three dense molecular cores TMC-1, TMC-1C, and L1521B in the Taurus molecular cloud complex to image the CCS 2{sub 1}-1{sub 0} transition. For all three sources, the clumpy CCS emission is most likely tracing the starless cores. However, these compact structures account for only {approx}1%-13% of the integrated emission detected in single-dish observations, indicating the presence of significant large-scale diffuse emission in favorable conditions for producing CCS.

  9. 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.

  10. 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.

  11. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    PubMed Central

    Sheikh, Arif; Polack, Berna; Rodriguez, Yvette; Kuker, Russ

    2017-01-01

    Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC) diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI) imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1). A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC. PMID:28117289

  12. 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

  13. 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.

  14. Imaging tumor microscopic viscosity in vivo using molecular rotors

    PubMed Central

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

    2017-01-01

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

  15. 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

  16. 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.

  17. 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.

  18. 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…

  19. 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...

  20. 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

  1. Spine labeling in axial magnetic resonance imaging via integral kernels.

    PubMed

    Miles, Brandon; Ben Ayed, Ismail; Hojjat, Seyed-Parsa; Wang, Michael H; Li, Shuo; Fenster, Aaron; Garvin, Gregory J

    2016-12-01

    This study investigates a fast integral-kernel algorithm for classifying (labeling) the vertebra and disc structures in axial magnetic resonance images (MRI). The method is based on a hierarchy of feature levels, where pixel classifications via non-linear probability product kernels (PPKs) are followed by classifications of 2D slices, individual 3D structures and groups of 3D structures. The algorithm further embeds geometric priors based on anatomical measurements of the spine. Our classifier requires evaluations of computationally expensive integrals at each pixel, and direct evaluations of such integrals would be prohibitively time consuming. We propose an efficient computation of kernel density estimates and PPK evaluations for large images and arbitrary local window sizes via integral kernels. Our method requires a single user click for a whole 3D MRI volume, runs nearly in real-time, and does not require an intensive external training. Comprehensive evaluations over T1-weighted axial lumbar spine data sets from 32 patients demonstrate a competitive structure classification accuracy of 99%, along with a 2D slice classification accuracy of 88%. To the best of our knowledge, such a structure classification accuracy has not been reached by the existing spine labeling algorithms. Furthermore, we believe our work is the first to use integral kernels in the context of medical images.

  2. Multimodality image guidance system integrating X-ray fluoroscopy and ultrasound image streams with electromagnetic tracking

    NASA Astrophysics Data System (ADS)

    Gutiérrez, Luis F.; Shechter, Guy; Stanton, Douglas; Dalal, Sandeep; Elgort, Daniel; Manzke, Robert; Chan, Raymond C.; Zagorchev, Lyubomir

    2007-03-01

    This work presents an integrated system for multimodality image guidance of minimally invasive medical procedures. This software and hardware system offers real-time integration and registration of multiple image streams with localization data from navigation systems. All system components communicate over a local area Ethernet network, enabling rapid and flexible deployment configurations. As a representative configuration, we use X-ray fluoroscopy (XF) and ultrasound (US) imaging. The XF imaging system serves as the world coordinate system, with gantry geometry derived from the imaging system, and patient table position tracked with a custom-built measurement device using linear encoders. An electromagnetic (EM) tracking system is registered to the XF space using a custom imaging phantom that is also tracked by the EM system. The RMS fiducial registration error for the EM to X-ray registration was 2.19 mm, and the RMS target registration error measured with an EM-tracked catheter was 8.81 mm. The US image stream is subsequently registered to the XF coordinate system using EM tracking of the probe, following a calibration of the US image within the EM coordinate system. We present qualitative results of the system in operation, demonstrating the integration of live ultrasound imaging spatially registered to X-ray fluoroscopy with catheter localization using electromagnetic tracking.

  3. Integrated editing system for Japanese text and image information "Linernote"

    NASA Astrophysics Data System (ADS)

    Tanaka, Kazuto

    Integrated Japanese text editing system "Linernote" developed by Toyo Industries Co. is explained. The system has been developed on the concept of electronic publishing. It is composed of personal computer NEC PC-9801 VX and other peripherals. Sentence, drawing and image data is inputted and edited under the integrated operating environment in the system and final text is printed out by laser printer. Handling efficiency of time consuming work such as pattern input or page make up has been improved by draft image data indication method on CRT. It is the latest DTP system equipped with three major functions, namly, typesetting for high quality text editing, easy drawing/tracing and high speed image processing.

  4. Quantification of bound microbubbles in ultrasound molecular imaging.

    PubMed

    Daeichin, Verya; Akkus, Zeynettin; Skachkov, Ilya; Kooiman, Klazina; Needles, Andrew; Sluimer, Judith; Janssen, Ben; Daemen, Mat J A P; van der Steen, Antonius F W; de Jong, Nico; Bosch, Johan G

    2015-06-01

    Molecular markers associated with diseases can be visualized and quantified noninvasively with targeted ultrasound contrast agent (t-UCA) consisting of microbubbles (MBs) that can bind to specific molecular targets. Techniques used for quantifying t-UCA assume that all unbound MBs are taken out of the blood pool few minutes after injection and only MBs bound to the molecular markers remain. However, differences in physiology, diseases, and experimental conditions can increase the longevity of unbound MBs. In such conditions, unbound MBs will falsely be quantified as bound MBs. We have developed a novel technique to distinguish and classify bound from unbound MBs. In the post-processing steps, first, tissue motion was compensated using block-matching (BM) techniques. To preserve only stationary contrast signals, a minimum intensity projection (MinIP) or 20th-percentile intensity projection (PerIP) was applied. The after-flash MinIP or PerIP was subtracted from the before-flash MinIP or PerIP. In this way, tissue artifacts in contrast images were suppressed. In the next step, bound MB candidates were detected. Finally, detected objects were tracked to classify the candidates as unbound or bound MBs based on their displacement. This technique was validated in vitro, followed by two in vivo experiments in mice. Tumors (n = 2) and salivary glands of hypercholesterolemic mice (n = 8) were imaged using a commercially available scanner. Boluses of 100 μL of a commercially available t-UCA targeted to angiogenesis markers and untargeted control UCA were injected separately. Our results show considerable reduction in misclassification of unbound MBs as bound ones. Using our method, the ratio of bound MBs in salivary gland for images with targeted UCA versus control UCA was improved by up to two times compared with unprocessed images.

  5. Integrating fossils with molecular phylogenies improves inference of trait evolution.

    PubMed

    Slater, Graham J; Harmon, Luke J; Alfaro, Michael E

    2012-12-01

    Comparative biologists often attempt to draw inferences about tempo and mode in evolution by comparing the fit of evolutionary models to phylogenetic comparative data consisting of a molecular phylogeny with branch lengths and trait measurements from extant taxa. These kinds of approaches ignore historical evidence for evolutionary pattern and process contained in the fossil record. In this article, we show through simulation that incorporation of fossil information dramatically improves our ability to distinguish among models of quantitative trait evolution using comparative data. We further suggest a novel Bayesian approach that allows fossil information to be integrated even when explicit phylogenetic hypotheses are lacking for extinct representatives of extant clades. By applying this approach to a comparative dataset comprising body sizes for caniform carnivorans, we show that incorporation of fossil information not only improves ancestral state estimates relative to those derived from extant taxa alone, but also results in preference of a model of evolution with trend toward large body size over alternative models such as Brownian motion or Ornstein-Uhlenbeck processes. Our approach highlights the importance of considering fossil information when making macroevolutionary inference, and provides a way to integrate the kind of sparse fossil information that is available to most evolutionary biologists.

  6. Integrated molecular profiling of SOD2 expression in multiple myeloma.

    PubMed

    Hurt, Elaine M; Thomas, Suneetha B; Peng, Benjamin; Farrar, William L

    2007-05-01

    Reactive oxygen species are known to be involved in several cellular processes, including cell signaling. SOD2 is a key enzyme in the conversion of reactive oxygen species and has been implicated in a host of disease states, including cancer. Using an integrated, whole-cell approach encompassing epigenetics, genomics, and proteomics, we have defined the role of SOD2 in multiple myeloma. We show that the SOD2 promoter is methylated in several cell lines and there is a correlative decrease in expression. Furthermore, myeloma patient samples have decreased SOD2 expression compared with healthy donors. Overexpression of SOD2 results in decreased proliferation and altered sensitivity to 2-methoxyestradiol-induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65 genes, including genes involved in tumorigenesis, and proteomic analysis identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated transcription factors identified 31 transcription factors with altered DNA binding activity, including XBP1, NFAT, forkhead, and GAS binding sites. Integration of data from our gestalt molecular analysis has defined a role for SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several transcription factors.

  7. Path-integral molecular dynamics simulation of diamond

    NASA Astrophysics Data System (ADS)

    Ramírez, Rafael; Herrero, Carlos P.; Hernández, Eduardo R.

    2006-06-01

    Diamond is studied by path-integral molecular dynamics simulations of the atomic nuclei in combination with a tight-binding Hamiltonian to describe its electronic structure and total energy. This approach allows us to quantify the influence of quantum zero-point vibrations and finite temperatures on both the electronic and vibrational properties of diamond. The electron-phonon coupling mediated by the zero-point vibration reduces the direct electronic gap of diamond by 10%. The calculated decrease of the direct gap with temperature shows good agreement with the experimental data available up to 700K . Anharmonic vibrational frequencies of the crystal have been obtained from a linear-response approach based on the path integral formalism. In particular, the temperature dependence of the zone-center optical phonon has been derived from the simulations. The anharmonicity of the interatomic potential produces a red shift of this phonon frequency. At temperatures above 500K , this shift is overestimated in comparison to available experimental data. The predicted temperature shift of the elastic constant c44 displays reasonable agreement with the available experimental results.

  8. Integral imaging based 3D display of holographic data.

    PubMed

    Yöntem, Ali Özgür; Onural, Levent

    2012-10-22

    We propose a method and present applications of this method that converts a diffraction pattern into an elemental image set in order to display them on an integral imaging based display setup. We generate elemental images based on diffraction calculations as an alternative to commonly used ray tracing methods. Ray tracing methods do not accommodate the interference and diffraction phenomena. Our proposed method enables us to obtain elemental images from a holographic recording of a 3D object/scene. The diffraction pattern can be either numerically generated data or digitally acquired optical data. The method shows the connection between a hologram (diffraction pattern) and an elemental image set of the same 3D object. We showed three examples, one of which is the digitally captured optical diffraction tomography data of an epithelium cell. We obtained optical reconstructions with our integral imaging display setup where we used a digital lenslet array. We also obtained numerical reconstructions, again by using the diffraction calculations, for comparison. The digital and optical reconstruction results are in good agreement.

  9. In vivo molecular profiling of human glioma using diffusion kurtosis imaging.

    PubMed

    Hempel, Johann-Martin; Bisdas, Sotirios; Schittenhelm, Jens; Brendle, Cornelia; Bender, Benjamin; Wassmann, Henk; Skardelly, Marco; Tabatabai, Ghazaleh; Vega, Salvador Castaneda; Ernemann, Ulrike; Klose, Uwe

    2017-01-01

    The purpose of this study is to assess the diagnostic performance of diffusion kurtosis imaging (DKI) for in vivo molecular profiling of human glioma. Normalized mean kurtosis (MKn) and mean diffusivity (MDn) metrics from DKI were assessed in 50 patients with histopathologically confirmed glioma. The results were compared in regard to the WHO-based histological findings and molecular characteristics leading to integrated diagnosis (Haarlem Consensus): isocitrate-dehydrogenase (IDH1/2) mutation status, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression, chromosome 1p/19q loss of heterozygosity (LOH), and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. MKn was significantly lower in tumors with IDH1/2 mutation (0.43 ± 0.09) and ATRX loss of expression (0.41 ± 0.11) than in those with IDH1/2 wild type (0.57 ± 0.09, p < 0.001) and ATRX maintained expression (0.51 ± 0.10, p = 0.004), respectively. Regarding the integrated molecular diagnosis, MKn was significantly higher in primary glioblastoma (0.57 ± 0.10) than in astrocytoma (0.39 ± 0.11, p < 0.001) and oligodendroglioma (0.47 ± 0.05, p = 0.003). MK may be used to provide insight into the human glioma molecular profile regarding IDH1/2 mutation status and ATRX expression. Considering the diagnostic and prognostic significance of these molecular markers, MK appears to be a promising in vivo biomarker for glioma. The diagnostic performance of MK seems to fit more with the integrated molecular approach than the conventional histological findings of the current WHO 2007 classification.

  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. Multifunctional nanoparticles for drug delivery and molecular imaging.

    PubMed

    Bao, Gang; Mitragotri, Samir; Tong, Sheng

    2013-01-01

    Recent advances in nanotechnology and growing needs in biomedical applications have driven the development of multifunctional nanoparticles. These nanoparticles, through nanocrystalline synthesis, advanced polymer processing, and coating and functionalization strategies, have the potential to integrate various functionalities, simultaneously providing (a) contrast for different imaging modalities, (b) targeted delivery of drug/gene, and (c) thermal therapies. Although still in its infancy, the field of multifunctional nanoparticles has shown great promise in emerging medical fields such as multimodal imaging, theranostics, and image-guided therapies. In this review, we summarize the techniques used in the synthesis of complex nanostructures, review the major forms of multifunctional nanoparticles that have emerged over the past few years, and provide a perceptual vision of this important field of nanomedicine.

  12. Molecular imaging in traditional Chinese medicine therapy for neurological diseases.

    PubMed

    Wang, Zefeng; Wan, Haitong; Li, Jinhui; Zhang, Hong; Tian, Mei

    2013-01-01

    With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM.

  13. Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases

    PubMed Central

    Wan, Haitong; Li, Jinhui; Zhang, Hong; Tian, Mei

    2013-01-01

    With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM. PMID:24222911

  14. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    PubMed Central

    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

  15. 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

  16. 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.

  17. Initial Investigation of Preclinical Integrated SPECT and MR Imaging

    PubMed Central

    Hamamura, Mark J.; Ha, Seunghoon; Roeck, Werner W.; Wagenaar, Douglas J.; Meier, Dirk; Patt, Bradley E.; Nalcioglu, Orhan

    2014-01-01

    Single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high-spatial resolution anatomical information as well as complementary functional information. In this study, we utilized a dual modality SPECT/MRI (MRSPECT) system to investigate the integration of SPECT and MRI for improved image accuracy. The MRSPECT system consisted of a cadmium-zinc-telluride (CZT) nuclear radiation detector interfaced with a specialized radiofrequency (RF) coil that was placed within a whole-body 4 T MRI system. The importance of proper corrections for non-uniform detector sensitivity and Lorentz force effects was demonstrated. MRI data were utilized for attenuation correction (AC) of the nuclear projection data and optimized Wiener filtering of the SPECT reconstruction for improved image accuracy. Finally, simultaneous dual-imaging of a nude mouse was performed to demonstrated the utility of co-registration for accurate localization of a radioactive source. PMID:20082527

  18. Geometric Modeling With Image Plane Integral (IPI) Holography

    NASA Astrophysics Data System (ADS)

    Lacey, D. C. L.

    1984-10-01

    Holography has long been considered to be an ideal method of visually presenting three-dimensional data which has been either experimentally acquired or mathematically calculated with a preconceived form in mind. Unfortunately, holograms have not had the image quality and accuracy to gain scientific acceptability outside the field of interferometric analysis. This paper will describe the use of an advanced composite holographic technique to give a clear, autostereoscopic image of a computer designed automotive part and a computer graphics concept of a molecule. The holograms were manufactured using Image Plane Integral (IPI) holography on an Argon laser printer designed and built by the author. The final holograms exhibited bright, achromatic, real images with high resolution and a minimum amount of controllable distortion. Additionally, because the IPI method uses a 35mm microfilmstrip for input, it could be universally applied as a hard copy format for presentation of almost any type of three-dimensional data base.

  19. 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.

  20. Purification of a low molecular weight fucoidan for SPECT molecular imaging of myocardial infarction.

    PubMed

    Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Azzouna, Rana Ben; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Guludec, Dominique Le; Letourneur, Didier; Chauvierre, Cédric

    2014-09-23

    Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome.

  1. Inflamed leukocyte-mimetic nanoparticles for molecular imaging of inflammation.

    PubMed

    Chen, Xiaoyue; Wong, Richard; Khalidov, Ildar; Wang, Andrew Y; Leelawattanachai, Jeerapond; Wang, Yi; Jin, Moonsoo M

    2011-10-01

    Dysregulated host inflammatory response causes many diseases, including cardiovascular and neurodegenerative diseases, cancer, and sepsis. Sensitive detection of the site of inflammation will, therefore, produce a wide-ranging impact on disease diagnosis and treatment. We hypothesized that nanoprobes designed to mimic the molecular interactions occurring between inflamed leukocytes and endothelium may possess selectivity toward diverse host inflammatory responses. To incorporate inflammation-sensitive molecular interactions, super paramagnetic iron oxide nanoparticles were conjugated with integrin lymphocyte function-associated antigen (LFA)-1 I domain, engineered to mimic activated leukocytes in physiology. Whole body optical and magnetic resonance imaging in vivo revealed that leukocyte-mimetic nanoparticles localized preferentially to the vasculature within and in the invasive front of the tumor, as well as to the site of acute inflammation. This study explored in vivo detection of tumor-associated vasculature with systemically injected inflammation-specific nanoparticles, presenting a possibility of tumor detection by inflamed tumor microenvironment.

  2. 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

  3. Design and fabrication of vertically-integrated CMOS image sensors.

    PubMed

    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.

  4. Characterization of low molecular weight alkoxylated polymers using long column SFC/MS and an image analysis based quantitation approach.

    PubMed

    Pinkston, J David; Marapane, Suresh B; Jordan, Glenn T; Clair, B David

    2002-10-01

    The utility of low viscosity mobile phases and long chromatographic columns for complex polymer analysis is demonstrated. We use long column supercritical fluid chromatography/mass spectrometry (SFC/MS) with electrospray ionization (ESI) to characterize a variety of complex, low molecular weight polymers. When quantitative analysis is desired, the resulting three-dimensional (time, intensity, and mass-to-charge ratio [m/z]) data are converted to images. Custom image analysis software is used to detect and integrate peaks in arbitrarily defined regions of the time-m/z map. These integrated peak volumes can be used to quantitate distinct component classes of the polymer mixtures.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  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. Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs

    PubMed Central

    Weber, Wolfgang A; Czernin, Johannes; Phelps, Michael E; Herschman, Harvey R

    2010-01-01

    SUMMARY Targeted drugs hold great promise for the treatment of malignant tumors; however, there are several challenges for efficient evaluation of these drugs in preclinical and clinical studies. These challenges include identifying the ‘correct’, biologically active concentration and dose schedule, selecting the patients likely to benefit from treatment, monitoring inhibition of the target protein or pathway, and assessing the response of the tumor to therapy. Although anatomic imaging will remain important, molecular imaging provides several new opportunities to make the process of drug development more efficient. Various techniques for molecular imaging that enable noninvasive and quantitative imaging are now available in the preclinical and clinical settings, to aid development and evaluation of new drugs for the treatment of cancer. In this Review, we discuss the integration of molecular imaging into the process of drug development and how molecular imaging can address key questions in the preclinical and clinical evaluation of new targeted drugs. Examples include imaging of the expression and inhibition of drug targets, noninvasive tissue pharmacokinetics, and early assessment of the tumor response. PMID:18097456

  11. 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

  12. Molecular imaging and therapy of cancer with radiolabeled nanoparticles

    PubMed Central

    Hong, Hao; Zhang, Yin; Sun, Jiangtao; Cai, Weibo

    2009-01-01

    Summary This review summarizes the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and internal radiotherapy applications targeting cancer. With the capacity to provide enormous flexibility, radiolabeled nanoparticles have the potential to profoundly impact disease diagnosis and patient management in the near future. Currently, the major challenges facing the research on radiolabeled nanoparticles are desirable (tumor) targeting efficacy, robust chemistry for both radionuclide encapsulation/incorporation and targeting ligand conjugation, favorable safety profile, as well as certain commercial and regulatory hurdles. PMID:20161038

  13. 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

  14. Non-Invasive Molecular Imaging of Disease Activity in Atherosclerosis

    PubMed Central

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

    2016-01-01

    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

  15. 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

  16. [Status and advances of RGD molecular imaging in lung cancer].

    PubMed

    Yue, Ning; Yuan, Shuanghu; Yang, Guoren

    2014-12-01

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

  17. 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.

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

    PubMed

    Yuan, Baohong; Rychak, Joshua

    2013-02-01

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

  20. [Consideration on molecular imaging technology as a tool for drug research and development].

    PubMed

    Yajima, Kazuyoshi; Nishimura, Shintaro

    2009-03-01

    Molecular imaging technology such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are known as powerful tools for clinical diagnosis in neurology, oncology and so on. As applications to new drug research and development, there are three methodologies which are PK (Pharmacokinetics study), PD (Pharmacodynamic study), and efficacy study. When we use these methodologies for the drug research, we must consider construction of technological environment (tracer, animal model, imaging analysis software, and clinical database) and regulatory environment for GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice) level. Additionally, concept of microdosing and exploratory clinical study was proposed in western countries and the guidance on microdosing study was also announced by Health, Labor and Welfare Ministry on June 3rd 2008. However they may be still in learning phase, we must meet with complexity, high cost, and indigestion. To promote molecular imaging technology into the drug research, integration of the scientists between academia and industry is important because it needs much type of the advanced technologies and skills.

  1. Integrated semiconductor optical sensors for cellular and neural imaging.

    PubMed

    Levi, Ofer; Lee, Thomas T; Lee, Meredith M; Smith, Stephen J; Harris, James S

    2007-04-01

    We review integrated optical sensors for functional brain imaging, localized index-of-refraction sensing as part of a lab-on-a-chip, and in vivo continuous monitoring of tumor and cancer stem cells. We present semiconductor-based sensors and imaging systems for these applications. Measured intrinsic optical signals and tissue optics simulations indicate the need for high dynamic range and low dark-current neural sensors. Simulated and measured reflectance spectra from our guided resonance filter demonstrate the capability for index-of-refraction sensing on cellular scales, compatible with integrated biosensors. Finally, we characterized a thermally evaporated emission filter that can be used to improve sensitivity for in vivo fluorescence sensing.

  2. Infrared properties of molecular cirrus. I - Photometry of extended sources on IRAS image products

    NASA Astrophysics Data System (ADS)

    Verter, Frances; Rickard, Lee J.

    1998-02-01

    We have conducted a survey of IRAS images of the high-latitude molecular cirrus clouds cataloged by Magnani et al. (1985). This paper reports the data reduction methods used in our survey and also studies the photometric accuracy that can be achieved for faint extended sources on IRAS image products. The principal topics covered are the modeling and removal of sky backgrounds at high Galactic latitude, and as a function of ecliptic latitude; the relative accuracy of different background models and methods of background removal; the integration of source flux on background-subtracted images; the proper definition of flux error bars, their calculation, and the minimum uncertainties set by the performance of the IRAS detectors; the creation of multiple-wavelength composite images; and the creation of temperature and opacity maps. We find that most error bars quoted for IRAS fluxes in the literature are incorrect. We conclude that the limiting surface brightness to which Sky Flux Plates may be used to study faint extended sources is approximately 0.05 MJy/sr. The photometric issues discussed herein are relevant to all IRAS image products, including Sky Flux Plates, co-added images, and the IRAS Sky Survey Atlas (ISSA). We compare the accuracy of data reduction on different products and discuss their relative advantages and disadvantages.

  3. Ab initio molecular orbital calculation considering the quantum mechanical effect of nuclei by path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Tachikawa, Masanori; Miura, Shinichi

    2000-12-01

    We present an accurate calculational scheme for many-body systems composed of electrons and nuclei, by path integral molecular dynamics technique combined with the ab initio molecular orbital theory. Based upon the scheme, the simulation of a water molecule at room temperature is demonstrated, applying all-electron calculation at the Hartree-Fock level of theory.

  4. 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.

  5. 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.

  6. A portable, integrated analyzer for microfluidic - based molecular analysis.

    PubMed

    Qiu, Xianbo; Chen, Dafeng; Liu, Changchun; Mauk, Michael G; Kientz, Terry; Bau, Haim H

    2011-10-01

    A portable, fully automated analyzer that provides actuation and flow control to a disposable, self-contained, microfluidic cassette ("chip") for point-of-care, molecular testing is described. The analyzer provides mechanical actuation to compress pouches that pump liquids in the cassette, to open and close diaphragm valves for flow control, and to induce vibrations that enhance stirring. The analyzer also provides thermal actuation for the temperature cycling needed for polymerase chain reaction (PCR) amplification of nucleic acids and for various drying processes. To improve the temperature uniformity of the PCR chamber, the system utilizes a double-sided heating/cooling scheme with a custom feedforward, variable, structural proportional-integral-derivative (FVSPID) controller. The analyzer includes a programmable central processing unit that directs the sequence and timing of the various operations and that is interfaced with a computer. The disposable cassette receives a sample, and it carries out cell lysis, nucleic acid isolation, concentration, and purification, thermal cycling, and either real time or lateral flow (LF) based detection. The system's operation was demonstrated by processing saliva samples spiked with B. cereus cells. The amplicons were detected with a lateral flow assay using upconverting phosphor reporter particles. This system is particularly suited for use in regions lacking centralized laboratory facilities and skilled personnel.

  7. Information content per photon versus image fidelity in three-dimensional photon-counting integral imaging.

    PubMed

    Hayat, Majeed M; Narravula, Srikanth; Pepin, Matthew; Javidi, Bahram

    2012-10-01

    Photon-counting integral imaging has been introduced recently, and its applications in three-dimensional (3D) object sensing, visualization, recognition, and classification under photon-starved conditions have been demonstrated. This paper sheds light on the underlying information-theoretic foundation behind the ability of photon-counting integral imaging in performing complex tasks with far fewer photons than conventional imaging systems. A metric for photon-information content is formulated in the context of 3D photon-counting imaging, and its properties are investigated. It is shown that there is an inherent trade-off between imaging fidelity, measured by the entropy-normalized mutual information associated with a given imaging system, and the amount of information in each photon used in the imaging process, as represented by the photon-number-normalized mutual information. The dependence of this trade-off on photon statistics, correlation in the 3D image, and the signal-to-noise ratio of the photon-detection system is also investigated.

  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. 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.

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

    PubMed Central

    Monroy-Contreras, Ricardo; Vaca, Luis

    2011-01-01

    Recent advances in RNA functional studies highlights the pivotal role of these molecules in cell physiology. Diverse methods have been implemented to measure the expression levels of various RNA species, using either purified RNA or fixed cells. Despite the fact that fixed cells offer the possibility to observe the spatial distribution of RNA, assays with capability to real-time monitoring RNA transport into living cells are needed to further understand the role of RNA dynamics in cellular functions. Molecular beacons (MBs) are stem-loop hairpin-structured oligonucleotides equipped with a fluorescence quencher at one end and a fluorescent dye (also called reporter or fluorophore) at the opposite end. This structure permits that MB in the absence of their target complementary sequence do not fluoresce. Upon binding to targets, MBs emit fluorescence, due to the spatial separation of the quencher and the reporter. Molecular beacons are promising probes for the development of RNA imaging techniques; nevertheless much work remains to be done in order to obtain a robust technology for imaging various RNA molecules together in real time and in living cells. The present work concentrates on the different requirements needed to use successfully MB for cellular studies, summarizing recent advances in this area. PMID:21876785

  11. 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

  12. Body image after bilateral prophylactic mastectomy: an integrative literature review.

    PubMed

    McGaughey, Amy

    2006-01-01

    Bilateral prophylactic mastectomy (BPM) can reduce a woman's risk for breast cancer by 80%. Thus, women who are at high risk for familial breast cancer are increasingly opting for BPM as a preventative option. Research indicates that there are psychological benefits to BPM, including a reduction in anxiety about developing breast cancer. The purpose of this integrative review is to summarize the research that has examined the effect of prophylactic mastectomy on women's subsequent body image. Thirteen studies were reviewed. The majority of women were satisfied with their decision. However, the majority of studies indicate that up to one-half of the women suffer a negative effect on body image and changes in sexuality. Knowledge of these findings can improve the practitioner's ability to counsel women regarding this radical decision. Further research, particularly prospective studies, are needed to examine women's body image prior to BPM so that the impact of prophylactic mastectomy can be examined more thoroughly.

  13. Terahertz imaging of metastatic lymph nodes using spectroscopic integration technique

    PubMed Central

    Park, Jae Yeon; Choi, Hyuck Jae; Cheon, Hwayeong; Cho, Seong Whi; Lee, Seungkoo; Son, Joo-Hiuk

    2017-01-01

    Terahertz (THz) imaging was used to differentiate the metastatic states of frozen lymph nodes (LNs) by using spectroscopic integration technique (SIT). The metastatic states were classified into three groups: healthy LNs, completely metastatic LNs, and partially metastatic LNs, which were obtained from three mice without infection and six mice infected with murine melanoma cells for 30 days and 15 days, respectively. Under histological examination, the healthy LNs and completely metastatic LNs were found to have a homogeneous cellular structure but the partially metastatic LNs had interfaces of the melanoma and healthy tissue. THz signals between the experimental groups were not distinguished at room temperature due to high attenuation by water in the tissues. However, a signal gap between the healthy and completely metastatic LNs was detected at freezing temperature. The signal gap could be enhanced by using SIT that is a signal processing method dichotomizing the signal difference between the healthy cells and melanoma cells with their normalized spectral integration. This technique clearly imaged the interfaces in the partially metastatic LNs, which could not be achieved by existing methods using a peak point or spectral value. The image resolution was high enough to recognize a metastatic area of about 0.7 mm size in the partially metastatic LNs. Therefore, this pilot study demonstrated that THz imaging of the frozen specimen using SIT can be used to diagnose the metastatic state of LNs for clinical application. PMID:28271007

  14. Fluorescence lifetime imaging of molecular rotors in living cells.

    PubMed

    Suhling, Klaus; Levitt, James A; Chung, Pei-Hua; Kuimova, Marina K; Yahioglu, Gokhan

    2012-02-09

    Diffusion is often an important rate-determining step in chemical reactions or biological processes and plays a role in a wide range of intracellular events. Viscosity is one of the key parameters affecting the diffusion of molecules and proteins, and changes in viscosity have been linked to disease and malfunction at the cellular level. While methods to measure the bulk viscosity are well developed, imaging microviscosity remains a challenge. Viscosity maps of microscopic objects, such as single cells, have until recently been hard to obtain. Mapping viscosity with fluorescence techniques is advantageous because, similar to other optical techniques, it is minimally invasive, non-destructive and can be applied to living cells and tissues. Fluorescent molecular rotors exhibit fluorescence lifetimes and quantum yields which are a function of the viscosity of their microenvironment. Intramolecular twisting or rotation leads to non-radiative decay from the excited state back to the ground state. A viscous environment slows this rotation or twisting, restricting access to this non-radiative decay pathway. This leads to an increase in the fluorescence quantum yield and the fluorescence lifetime. Fluorescence Lifetime Imaging (FLIM) of modified hydrophobic BODIPY dyes that act as fluorescent molecular rotors show that the fluorescence lifetime of these probes is a function of the microviscosity of their environment. A logarithmic plot of the fluorescence lifetime versus the solvent viscosity yields a straight line that obeys the Förster Hoffman equation. This plot also serves as a calibration graph to convert fluorescence lifetime into viscosity. Following incubation of living cells with the modified BODIPY fluorescent molecular rotor, a punctate dye distribution is observed in the fluorescence images. The viscosity value obtained in the puncta in live cells is around 100 times higher than that of water and of cellular cytoplasm. Time-resolved fluorescence anisotropy

  15. Recent advances in visualizing vulnerable plaque: focus on noninvasive molecular imaging.

    PubMed

    Bala, Gezim; Cosyns, Bernard

    2014-09-01

    Traditional imaging methods in atherosclerosis have focused primarily on anatomic information. Imaging approaches that visualize molecular targets rather than anatomic structures may emphasize biologic aspects of atherosclerosis. Molecular imaging of atherosclerotic lesions has become a crucial experimental tool and is now emerging in the clinical arena. In this review, we briefly highlight the rationale and fundamental principles of molecular imaging. We then discuss the promising imaging modalities, along with their potential limitations, and the molecular targets being investigated in experimental research. Finally, we summarize the most important clinical studies recently performed in humans.

  16. Image segmentation for integrated multiphoton microscopy and reflectance confocal microscopy imaging of human skin in vivo

    PubMed Central

    Chen, Guannan; Lui, Harvey

    2015-01-01

    Background Non-invasive cellular imaging of the skin in vivo can be achieved in reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) modalities to yield complementary images of the skin based on different optical properties. One of the challenges of in vivo microscopy is the delineation (i.e., segmentation) of cellular and subcellular architectural features. Methods In this work we present a method for combining watershed and level-set models for segmentation of multimodality images obtained by an integrated MPM and RCM imaging system from human skin in vivo. Results Firstly, a segmentation model based on watershed is introduced for obtaining the accurate structure of cell borders from the RCM image. Secondly,, a global region based energy level-set model is constructed for extracting the nucleus of each cell from the MPM image. Thirdly, a local region-based Lagrange Continuous level-set approach is used for segmenting cytoplasm from the MPM image. Conclusions Experimental results demonstrated that cell borders from RCM image and boundaries of cytoplasm and nucleus from MPM image can be obtained by our segmentation method with better accuracy and effectiveness. We are planning to use this method to perform quantitative analysis of MPM and RCM images of in vivo human skin to study the variations of cellular parameters such as cell size, nucleus size and other mophormetric features with skin pathologies. PMID:25694949

  17. FLIM and SLIM for molecular imaging in PDT

    NASA Astrophysics Data System (ADS)

    Rueck, Angelika C.; Dolp, Frank; Huelshoff, Christian; Hauser, Carmen; Scalfi-Happ, Claudia

    2005-03-01

    Various problems arising during molecular imaging of different fluoroprobes and metabolites used in photodynamic therapy could be circumvented by focusing on time-resolved detection. For this, an interesting new method seems to be time-correlated single photon counting, where a time-to-amplitude converter determines the temporal position and a scanning interface connected to the scanning unit of a laser microscope determines the spatial location of a signal. In combination with spectral resolved detection (spectral lifetime imaging) the set-up achieves the features of highly sophisticated lifetime imaging systems. The photoactive substance on which 5-ALA PDT is based, is protoporphyrine IX which is synthesized in mitochondria. Alternatively, other metabolites from 5-ALA could be involved. Subcellular differentiation of those metabolites without extensive extraction procedures is not trivial, because of highly overlapping spectral properties. Measuring the fluorescence lifetime on a subcellular level could be a successful alternative. To record lifetime images (τ-mapping) a setup consisting on a laser scanning microscope equipped with detection units for time-correlated single photon counting and ps diode lasers for short-pulsed excitation was implemented. The time-resolved fluorescence characteristics of 5-ALA metabolites were investigated in solution and in cell culture. The lifetimes were best fitted by a biexponential fitting routine. Different lifetimes could be found in different cell compartments. During illumination, the lifetimes decreased significantly. Different metabolites of 5-ALA could be correlated with different fluorescence lifetimes. In addition cells were coincubated with the nuclear staining dye DAPI, in order to investigate the cell cycle. Using appropriate filtering or alternatively spectral lifetime imaging the time-resolved fluorescence of DAPI could be very well distinguished from 5-ALA-metabolites. In contrast to ALA, the lifetime of DAPI

  18. 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.

  19. Velocity map imaging with non-uniform detection: Quantitative molecular axis alignment measurements via Coulomb explosion imaging.

    PubMed

    Underwood, Jonathan G; Procino, I; Christiansen, L; Maurer, J; Stapelfeldt, H

    2015-07-01

    We present a method for inverting charged particle velocity map images which incorporates a non-uniform detection function. This method is applied to the specific case of extracting molecular axis alignment from Coulomb explosion imaging probes in which the probe itself has a dependence on molecular orientation which often removes cylindrical symmetry from the experiment and prevents the use of standard inversion techniques for the recovery of the molecular axis distribution. By incorporating the known detection function, it is possible to remove the angular bias of the Coulomb explosion probe process and invert the image to allow quantitative measurement of the degree of molecular axis alignment.

  20. MOLECULAR AND IONIZED HYDROGEN IN 30 DORADUS. I. IMAGING OBSERVATIONS

    SciTech Connect

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

    2015-07-10

    We present the first fully calibrated H{sub 2} 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 H{sub 2}-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 H{sub 2}, Brγ, CO, and 8 μm emission, the H{sub 2} to Brγ line ratio, and Cloudy models, we find that the H{sub 2} 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 <10{sup 4} cm{sup −3}. Comparisons with Brγ, 8 μm, and CO emission indicate that H{sub 2} emission is due to fluorescence, and provide no evidence for shock excited emission of this line.

  1. Protocols for three-dimensional molecular imaging using mass spectrometry.

    PubMed

    Wucher, Andreas; Cheng, Juan; Winograd, Nicholas

    2007-08-01

    A protocol for three-dimensional molecular thin-film analysis is described that utilizes imaging time-of-flight secondary ion mass spectrometry and large-area atomic force microscopy. As a test study, a 300-nm trehalose film deposited on a Si substrate was structured by bombardment with a focused 15-keV Ga+ ion beam and analyzed using a 40-keV C60+ cluster ion beam. A three-dimensional sputter depth profile was acquired as a series of high-resolution lateral SIMS images with intermittent erosion cycles. As the most important result of this study, we find that the structured film exhibits a highly nonuniform erosion rate, thus preventing a simple conversion of primary ion fluence into eroded depth. Instead, the depth scale calibration must be performed individually on each pixel of the imaged area. The resulting laterally resolved depth profiles are discussed in terms of the chemical damage induced by the Ga+ bombardment along with the physics of the C60+ induced erosion process.

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

    PubMed

    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.

  3. 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.

  4. Ambient Ionization and FAIMS Mass Spectrometry for Enhanced Imaging of Multiply Charged Molecular Ions in Biological Tissues

    PubMed Central

    Feider, Clara L.; Elizondo, Natalia

    2017-01-01

    Ambient ionization mass spectrometry imaging (MSI) has been increasingly used to investigate the molecular distribution of biological tissue samples. Here, we report the integration and optimization of desorption electrospray ionization (DESI) and liquid-microjunction surface sampling probe (LMJ-SSP) with a chip-based high-field asymmetric waveform ion mobility spectrometry (FAIMS) device to image metabolites, lipids, and proteins in biological tissue samples. Optimized FAIMS parameters for specific molecular classes enabled semitargeted detection of multiply charged molecular species at enhanced signal-to-noise ratios (S/N), improved visualization of spatial distributions, and, most importantly, allowed detection of species which were unseen by ambient ionization MSI alone. Under static DESI-FAIMS conditions selected for transmission of doubly charged cardiolipins (CL), for example, detection of 71 different CL species was achieved in rat brain, 23 of which were not observed by DESI alone. Diagnostic CL were imaged in a human thyroid tumor sample with reduced interference of isobaric species. LMJ-SSP-FAIMS enabled detection of 84 multiply charged protein ions in rat brain tissue, 66 of which were exclusive to this approach. Spatial visualization of proteins in substructures of rat brain, and in human ovarian cancerous, necrotic, and normal tissues was achieved. Our results indicate that integration of FAIMS with ambient ionization MS allows improved detection and imaging of selected molecular species. We show that this methodology is valuable in biomedical applications of MSI for detection of multiply charged lipids and proteins from biological tissues. PMID:27782388

  5. Three-dimensional identification of biological microorganism using integral imaging

    NASA Astrophysics Data System (ADS)

    Javidi, Bahram; Moon, Inkyu; Yeom, Seokwon

    2006-12-01

    In this paper, we address the identification of biological microorganisms using microscopic integral imaging (II). II senses multi-view directional information of 3D objects illuminated by incoherent light. A micro-lenslet array generates a set of elemental images by projecting a 3D scene onto a detector array. In computational reconstruction of II, 3D volumetric scenes are numerically reconstructed by means of a geometrical ray projection method. The identification of the biological samples is performed using the 3D volume of the reconstructed object. In one approach, the multivariate statistical distribution of the reference sample is measured in 3D space and compared with an unknown input sample by means of statistical discriminant functions. The multivariate empirical cumulative density of the 3D volume image is determined for classification. On the other approach, the graph matching technique is applied to 3D volumetric images with Gabor feature extraction. The reference morphology is identified in unknown input samples using 3D grids. Experimental results are presented for the identification of sphacelaria alga and tribonema aequale alga. We present experimental results for both 3D and 2D imaging. To the best of our knowledge, this is the first report on 3D identification of microorganisms using II.

  6. Three-dimensional identification of biological microorganism using integral imaging.

    PubMed

    Javidi, Bahram; Moon, Inkyu; Yeom, Seokwon

    2006-12-11

    In this paper, we address the identification of biological microorganisms using microscopic integral imaging (II). II senses multi-view directional information of 3D objects illuminated by incoherent light. A micro-lenslet array generates a set of elemental images by projecting a 3D scene onto a detector array. In computational reconstruction of II, 3D volumetric scenes are numerically reconstructed by means of a geometrical ray projection method. The identification of the biological samples is performed using the 3D volume of the reconstructed object. In one approach, the multivariate statistical distribution of the reference sample is measured in 3D space and compared with an unknown input sample by means of statistical discriminant functions. The multivariate empirical cumulative density of the 3D volume image is determined for classification. On the other approach, the graph matching technique is applied to 3D volumetric images with Gabor feature extraction. The reference morphology is identified in unknown input samples using 3D grids. Experimental results are presented for the identification of sphacelaria alga and tribonema aequale alga. We present experimental results for both 3D and 2D imaging. To the best of our knowledge, this is the first report on 3D identification of microorganisms using II.

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

    NASA Astrophysics Data System (ADS)

    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 × 20.0 mm dimensions could

  8. 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

  9. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  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. Solution processed integrated pixel element for an imaging device

    NASA Astrophysics Data System (ADS)

    Swathi, K.; Narayan, K. S.

    2016-09-01

    We demonstrate the implementation of a solid state circuit/structure comprising of a high performing polymer field effect transistor (PFET) utilizing an oxide layer in conjunction with a self-assembled monolayer (SAM) as the dielectric and a bulk-heterostructure based organic photodiode as a CMOS-like pixel element for an imaging sensor. Practical usage of functional organic photon detectors requires on chip components for image capture and signal transfer as in the CMOS/CCD architecture rather than simple photodiode arrays in order to increase speed and sensitivity of the sensor. The availability of high performing PFETs with low operating voltage and photodiodes with high sensitivity provides the necessary prerequisite to implement a CMOS type image sensing device structure based on organic electronic devices. Solution processing routes in organic electronics offers relatively facile procedures to integrate these components, combined with unique features of large-area, form factor and multiple optical attributes. We utilize the inherent property of a binary mixture in a blend to phase-separate vertically and create a graded junction for effective photocurrent response. The implemented design enables photocharge generation along with on chip charge to voltage conversion with performance parameters comparable to traditional counterparts. Charge integration analysis for the passive pixel element using 2D TCAD simulations is also presented to evaluate the different processes that take place in the monolithic structure.

  13. ISGRI: a CdTe array imager for INTEGRAL

    NASA Astrophysics Data System (ADS)

    Lebrun, Francois; Blondel, Claire; Fondeur, Irene; Goldwurm, Andrea; Laurent, Phillipe; Leray, Jean P.

    1996-10-01

    The INTEGRAL soft gamma-ray imager (ISGRI) is a large and thin CdTe array. Operating at room temperature, this gamma camera covers the lower part (below 200 keV) of the energy domain (20 keV - 10 MeV) of the imager on board the INTEGRAL Satellite (IBIS). The ASIC's front-end electronics features particularly a low noise preamplifier, allowing a threshold below 20 keV and a pulse rise-time measurement which permits a charge loss correction. The charge loss correction and its performances are presented as well as the results of various studies on CdTe thermal behavior and radiation hardness. At higher energy (above 200 keV) ISGRI will operate in conjunction with PICsIT, the IBIS CsI gamma camera. A selection among the events in coincidence performed on the basis of the Compton scattering properties reduces strongly the background. This allows an improvement of the sensitivity and permits short term imaging and spectral studies (high energy pulsars) which otherwise would not have fit within the IBIS telemetry allocation.

  14. Dictionary-based image reconstruction for superresolution in integrated circuit imaging.

    PubMed

    Cilingiroglu, T Berkin; Uyar, Aydan; Tuysuzoglu, Ahmet; Karl, W Clem; Konrad, Janusz; Goldberg, Bennett B; Ünlü, M Selim

    2015-06-01

    Resolution improvement through signal processing techniques for integrated circuit imaging is becoming more crucial as the rapid decrease in integrated circuit dimensions continues. Although there is a significant effort to push the limits of optical resolution for backside fault analysis through the use of solid immersion lenses, higher order laser beams, and beam apodization, signal processing techniques are required for additional improvement. In this work, we propose a sparse image reconstruction framework which couples overcomplete dictionary-based representation with a physics-based forward model to improve resolution and localization accuracy in high numerical aperture confocal microscopy systems for backside optical integrated circuit analysis. The effectiveness of the framework is demonstrated on experimental data.

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

    PubMed

    Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

    2013-10-01

    Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  16. 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

  17. Integrated microscopy for real-time imaging of mechanotransduction studies in live cells

    NASA Astrophysics Data System (ADS)

    Trache, Andreea; Lim, Soon-Mi

    2009-05-01

    Mechanical force is an important stimulus and determinant of many vascular smooth muscle cell functions including contraction, proliferation, migration, and cell attachment. Transmission of force from outside the cell through focal adhesions controls the dynamics of these adhesion sites and initiates intracellular signaling cascades that alter cellular behavior. To understand the mechanism by which living cells sense mechanical forces, and how they respond and adapt to their environment, a critical first step is to develop a new technology to investigate cellular behavior at subcellular level that integrates an atomic force microscope (AFM) with total internal reflection fluorescence (TIRF) and fast-spinning disk (FSD) confocal microscopy, providing high spatial and temporal resolution. AFM uses a nanosensor to measure the cell surface topography and can apply and measure mechanical force with high precision. TIRF microscopy is an optical imaging technique that provides high-contrast images with high z-resolution of fluorescently labeled molecules in the immediate vicinity of the cell-coverslip interface. FSD confocal microscopy allows rapid 3-D imaging throughout the cell in real time. The integrated system is broadly applicable across a wide range of molecular dynamic studies in any adherent live cells, allowing direct optical imaging of cell responses to mechanical stimulation in real time.

  18. Skin aging: molecular pathology, dermal remodelling and the imaging revolution.

    PubMed

    Newton, V L; Mcconnell, J C; Hibbert, S A; Graham, H K; Watson, R E

    2015-12-01

    Skin is a multifunctional organ but, alongside every other organ system, is subject to both intrinsic (chronological) and extrinsic (environmental) aging, resulting in a loss of functional capacity. Cutaneous aging manifests as an observable change in the external appearance of the skin, the major accelerator of the aging process being our interactions with our environment, such as chronic exposure to solar irradiation (UV, IR or visible wavelengths of light). The aim of this contribution, therefore, was to provide a review of the pathological mechanisms which may play roles in the development of extrinsic, mainly photo-, aging and to review how these molecular changes impact on the structure of the organ as a whole, resulting in loss of function. Finally, we will describe the advances which are occurring in imaging techniques which may allow further characterisation of aged skin.

  19. Optical methods for molecular sensing: Supplementing imaging of tissue microstructure with molecular information

    NASA Astrophysics Data System (ADS)

    Winkler, Amy Marie

    More and more researchers and clinicians are looking to molecular sensing to predict how cells will behave, seeking the answers to questions like will these tumor cells become malignant? or how will these cells respond to chemotherapy? Optical methods are attractive for answering these questions because optical radiation is safer and less expensive than alternative methods, such as CT which uses X-ray radiation, PET/SPECT which use gamma radiation, or MRI which is expensive and only available in a hospital setting. In this dissertation, three distinct optical methods are explored to detect at the molecular level: optical coherence tomography (OCT), laser-induced fluorescence (LIF), and optical polarimetry. OCT has the capability to simultaneously capture anatomical information as well as molecular information using targeted contrast agents such as gold nanoshells. LIF is less useful for capturing anatomical information, but it can achieve significantly better molecular sensitivity with the use of targeted fluorescent dyes. Optical polarimetry has potential to detect the concentration of helical molecules, such as glucose. All of these methods are noninvasive or minimally invasive. The work is organized into four specific aims. The first is the design and implementation of a fast, high resolution, endoscopic OCT system to facilitate minimally invasive mouse colon imaging. The second aim is to demonstrate the utility of this system for automatically identifying tumor lesions based on tissue microstructure. The third is to demonstrate the use of contrast agents to detect molecular expression using OCT and LIF. The last aim is to demonstrate a new method based on optical polarimetry for noninvasive glucose sensing.

  20. 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.

  1. 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.

  2. Time slicing in 3D momentum imaging of the hydrogen molecular ion photo-fragmentation

    NASA Astrophysics Data System (ADS)

    Kaya, N.; Kaya, G.; Pham, F. V.; Strohaber, J.; Kolomenskii, A. A.; Schuessler, H. A.

    2017-02-01

    Photo-fragmentation of the hydrogen molecular ion was investigated with 800 nm, 50 fs laser pulses by employing a time slicing 3D imaging technique that enables the simultaneous measurement of all three momentum components which are linearly related with the pixel position and slicing time. This is done for each individual product particle arriving at the detector. This mode of detection allows us to directly measure the three-dimensional fragment momentum vector distribution without having to rely on mathematical reconstruction methods, which additionally require the investigated system to be cylindrically symmetric. We experimentally reconstruct the laser-induced photo-fragmentation of the hydrogen molecular ion. In previous experiments, neutral molecules were used as a target, but in this work, performed with molecular ions, the initial vibrational level populations are well-defined after electron bombardment, which facilitates the interpretation. We show that the employed time-slicing technique allows us to register the fragment momentum distribution that reflects the initial molecular states with greater detail, revealing features that were concealed in the full time-integrated distribution on the detector.

  3. 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.

  4. 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

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

    PubMed

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

    2015-04-01

    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.

  6. Image pixel device using integrated organic electronic components

    NASA Astrophysics Data System (ADS)

    Swathi, K.; Narayan, K. S.

    2016-11-01

    We report a solution processed, monolithically integrated device similar to an imaging pixel element used in complementary metal-oxide semiconductor (CMOS) based cameras. This integrated pixel essentially consists of a pair of organic photodiode (OPD) and organic field effect transistor (OFET). The signal generated by the light responsive OPD drives the OFET to different output states to quantify the light intensity. The prerequisite of a low operating voltage OFET (<2 V) was achieved using a bottom-gate, top-contact OFET consisting of a high mobility polymer semiconductor and a self-assembled hybrid dielectric layer. A bulk heterojunction blend was used as the photo-active layer in the OPD along with suitable buffer layers for charge extraction. The material parameters were optimized to realize a suitable structure which clearly demonstrated the interplay of the OPD and OFET operations, thereby forming a roadmap for all-organic CMOS arrays.

  7. 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

  8. Molecular photoacoustic imaging using gold nanoparticles as a contrast agent

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher P.; Zhang, Qiang; Cobley, Claire M.; Xia, Younan; Wang, Lihong V.

    2010-02-01

    Gold nanoparticles have received much attention due to their potential diagnostic and therapeutic applications. Gold nanoparticles are attractive in many biomedical applications because of their biocompatibility, easily modifiable surfaces for targeting, lack of heavy metal toxicity, wide range of sizes (35-100 nm), tunable plasmonic resonance peak, encapsulated site-specific drug delivery, and strong optical absorption in the near-infrared regime. Specifically, due to their strong optical absorption, gold nanoparticles have been used as a contrast agent for molecular photoacoustic (PA) imaging of tumor. The plasmonic resonance peak of the gold nanocages (AuNCs) was tuned to the near-infrared region, and the ratio of the absorption cross-section to the extinction cross-section was approximately ~70%, as measured by PA sensing. We used PEGylated gold nanocages (PEG-AuNCs) as a passive targeting contrast agent on melanomas. After 6-h intravenous injection of PEG-AuNCs, PA amplitude was increased by ~14 %. These results strongly suggest PA imaging paired with AuNCs is a promising diagnostic tool for early cancer detection.

  9. Purification of a Low Molecular Weight Fucoidan for SPECT Molecular Imaging of Myocardial Infarction

    PubMed Central

    Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Ben Azzouna, Rana; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Le Guludec, Dominique; Letourneur, Didier; Chauvierre, Cédric

    2014-01-01

    Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome. PMID:25251032

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

    DTIC Science & Technology

    2007-07-01

    51nipple, Phyllodes Tumor , and tubular carcinoma.3 52Breast cancer is grouped into stages which 53indicate the invasiveness of the disease. There 54are...enhances the tumor MR image contrast but is also an excellent probe for optical imaging. We have established three breast cancer tumor models...magnetic resonance imaging (MRI), and optical imaging techniques for better imaging of tumors . In vivo molecular imaging, which utilizes these two

  11. Molecular Imaging Markers to Track Huntington’s Disease Pathology

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  13. Imaging in arthritis: quantifying effects of therapeutic intervention using MRI and molecular imaging.

    PubMed

    Cimmino, Marco A; Barbieri, Francesca; Zampogna, Giuseppe; Camellino, Dario; Paparo, Francesco; Parodi, Massimiliano

    2012-01-05

    Modern imaging techniques are becoming increasingly important in assessing the course of arthritis and in permitting measurement of response to treatment as part of the follow-up of patients. They include ultrasonography (US), MRI, PET/CT, and biofluorescence. In patients with rheumatoid arthritis, clinical evaluation is significantly less sensitive than either US or MRI in detecting synovitis. As a result, imaging is a useful alternative to achieving proper assessment of disease activity. The different areas in which the new imaging techniques could help practicing rheumatologists and internal physicians include the following: early and differential diagnosis of arthritis, evaluation of disease activity, prognosis, assessment of treatment efficacy, assessment of remission, and evaluation of subclinical disease. MRI is probably the best imaging method to study disease activity in RA, because it can study all the joints with similar efficacy, has been sufficiently standardised, and yields data on inflammation that can be quantified. Different methods, developed to score synovitis activity, are increasingly used in clinical trials. The main application of PET/CT in rheumatology is the diagnosis and follow-up of large vessel vasculitis. More recently, also RA disease activity has been evaluated, allowing a panoramic view of the patient. Molecular imaging studies molecular and cellular processes in intact living organisms in a non-invasive fashion. In fluorescence, dyes, that emit light upon excitation by a light source and are read by a camera, can be used to show inflamed areas where neoangiogenesis, vasodilatation, and increased vessel permeability are present. These dyes can be coupled with different compounds including antibodies and drugs.

  14. 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.

  15. Analytic evaluation of two-center molecular integrals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1986-01-01

    By using the Fourier-transform technique, the explicit expressions for the one-electron - two-center overlap integrals of Slater-type atomic orbitals up to 3d are derived. The final expressions are analytic, simple, and independent of local coordinates. Furthermore, they do not contain the nonclosed-form of exponential integrals which were presented in expressions given in earlier work. It is shown that the two-electron - two-center Coulomb integrals, as well as the hybrid integrals, can simply be expressed in terms of these integrals. The numerical instability arising from the situation in which the exponents of the two orbitals are almost equal is discussed, and a solution for this problem based on a Taylor-series expansion of the integral is suggested.

  16. 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.

  17. HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

    PubMed Central

    Qiao, Jingjuan; Li, Shunyi; Wei, Lixia; Jiang, Jie; Long, Robert; Mao, Hui; Wei, Ling; Wang, Liya; Yang, Hua; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2011-01-01

    The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery. PMID:21455310

  18. 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.

  19. 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.

  20. Fluorescence-integrated transmission electron microscopy images: integrating fluorescence microscopy with transmission electron microscopy.

    PubMed

    Sims, Paul A; Hardin, Jeff D

    2007-01-01

    This chapter describes high-pressure freezing (HPF) techniques for correlative light and electron microscopy on the same sample. Laser scanning confocal microscopy (LSCM) is exploited for its ability to collect fluorescent, as well as transmitted and back scattered light (BSL) images at the same time. Fluorescent information from a whole mount (preembedding) or from thin sections (post-embedding) can be displayed as a color overlay on transmission electron microscopy (TEM) images. Fluorescence-integrated TEM (F-TEM) images provide a fluorescent perspective to TEM images. The pre-embedding method uses a thin two-part agarose pad to immobilize live Caenorhabditis elegans embryos for LSCM, HPF, and TEM. Pre-embedding F-TEM images display fluorescent information collected from a whole mount of live embryos onto all thin sections collected from that sample. In contrast, the postembedding method uses HPF and freeze substitution with 1% paraformaldehyde in 95% ethanol followed by low-temperature embedding in methacrylate resin. This procedure preserves the structure and function of green fluorescent protein (GFP) as determined by immunogold labeling of GFP, when compared with GFP expression, both demonstrated in the same thin section.

  1. Integrating DICOM conformant imaging equipment with a PACS

    NASA Astrophysics Data System (ADS)

    Duerinckx, Andre J.; Harmon, Craig; Crook, Michael; Grant, Edward G.

    1998-07-01

    Purpose/Background: As medical centers purchase commercial PACS to integrate with their imaging equipment, the fact that each component is often purchased at different times and with differing levels of DICOM conformance may become a problem. When the PACS is installed, major incompatibilities are often discovered between DICOM conformant pieces of equipment. Commercial PACS vendors are sometimes reluctant to take responsibility for the final integration of these components. The purpose of this paper is to document the nature and extent of these problem at one medical center, to report on how we are trying to solve them, and recommendations for the future. Methods: A large commercial PACS (IMPAXTM, Bayer Corporation, Agfa division) installed at the West Los Angeles VA medical Center was recently upgraded to be DICOM 3.0 conformant. Recently purchased DICOM conformant CT and MRI units and an older CT were already present. The problems in interfacing and integrating these imaging modalities with the upgraded DICOM-compliant PACS were investigated. Both software and hardware incompatibilities and human factors in bringing the different commercial vendors together were analyzed. Results: Major hardware and software incompatibilities were discovered. The use of DICOM-gateways is not always able to solve problems of incompatibility. The typical lag time between discovery of a problem and provision of a solution was 4 to 5 months. For more severe problems and also for a few of the lesser problems, resolution took over a year and is still ongoing. Repeated requests had to be made to the vendors to get together with us and solve these problems.

  2. Integrated Colony Imaging, Analysis, and Selection Device for Regenerative Medicine.

    PubMed

    Kwee, Edward; Herderick, Edward E; Adams, Thomas; Dunn, James; Germanowski, Robert; Krakosh, Frank; Boehm, Cynthia; Monnich, James; Powell, Kimerly; Muschler, George

    2017-04-01

    Stem and progenitor cells derived from human tissues are being developed as cell sources for cell-based assays and therapies. However, tissue-derived stem and progenitor cells are heterogeneous. Differences in observed clones of stem cells likely reflect important aspects of the underlying state of the source cells, as well as future potency for cell therapies. This paper describes a colony analysis and picking device that provides quantitative analysis of heterogeneous cell populations and precise tools for cell picking for research or biomanufacturing applications. We describe an integrated robotic system that enables image acquisition and automated image analysis to be coupled with rapid automated selection of individual colonies in adherent cell cultures. Other automated systems have demonstrated feasibility with picking from semisolid media or off feeder layers. We demonstrate the capability to pick adherent bone-derived stem cells from tissue culture plastic. Cells are efficiently picked from a target site and transferred to a recipient well plate. Cells demonstrate viability and adherence and maintain biologic potential for surface markers CD73 and CD90 based on phase contrast and fluorescence imaging 6 days after transfer. Methods developed here can be applied to the study of other stem cell types and automated culture of cells.

  3. Medical image integrity control and forensics based on watermarking--approximating local modifications and identifying global image alterations.

    PubMed

    Huang, H; Coatrieux, G; Shu, H Z; Luo, L M; Roux, Ch

    2011-01-01

    In this paper we present a medical image integrity verification system that not only allows detecting and approximating malevolent local image alterations (e.g. removal or addition of findings) but is also capable to identify the nature of global image processing applied to the image (e.g. lossy compression, filtering …). For that purpose, we propose an image signature derived from the geometric moments of pixel blocks. Such a signature is computed over regions of interest of the image and then watermarked in regions of non interest. Image integrity analysis is conducted by comparing embedded and recomputed signatures. If any, local modifications are approximated through the determination of the parameters of the nearest generalized 2D Gaussian. Image moments are taken as image features and serve as inputs to one classifier we learned to discriminate the type of global image processing. Experimental results with both local and global modifications illustrate the overall performances of our approach.

  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. MALDI imaging mass spectrometry of integral membrane proteins from ocular lens and retinal tissue.

    PubMed

    Grey, Angus C; Chaurand, Pierre; Caprioli, Richard M; Schey, Kevin L

    2009-07-01

    A tissue preparation protocol for MALDI (matrix-assisted laser desorption/ionization) imaging mass spectrometry of integral membrane proteins was developed using ocular lens and retinal tissues as model samples. Frozen bovine and human lenses were cryosectioned equatorially or axially at -20 degrees C into 20 mum-thick tissue sections. Lens sections were mounted onto gold-coated MALDI targets by methanol soft-landing to maintain tissue integrity. Tissue sections underwent extensive water washing to deplete the samples of highly abundant water-soluble proteins. Automated matrix deposition was achieved using an acoustic reagent multispotter, with sinapinic acid as matrix and high percentage acetonitrile as solvent, with a center-to-center spot spacing of 200-300 mum. Molecular images of full-length Aquaporin-0 (AQP0) and its most abundant truncation products were obtained from mass spectral data acquired across whole bovine and human lens sections. In equatorial and axial sections of bovine lenses, full-length AQP0 was detected throughout the lens. A truncation product corresponding to AQP0 (1-260) was detected in the bovine lens core at low abundance. In axial lens sections, no antero-posterior variation was detected. In 11 year-old human lens sections, full-length AQP0 was most abundant in the lens periphery, but was detected throughout the lens. The major truncation product, consisting of AQP0 residues 1-246, was absent from the lens periphery and increased in abundance in the lens core. This tissue preparation protocol was then applied to image the distribution of the G-protein coupled receptor, opsin, in the rabbit retina. This protocol has expanded the variety of target analytes which can be detected by MALDI imaging mass spectrometry to include intact integral membrane proteins.

  6. 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.…

  7. 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.

  8. Robust integral image rectification framework using perspective transformation supported by statistical line segment clustering.

    PubMed

    Koufogiannis, E T; Sgouros, N P; Sangriotis, M S

    2011-12-01

    In most integral image analysis and processing tasks, accurate knowledge of the internal image structure is required. In this paper we present a robust framework for the accurate rectification of perspectively distorted integral images based on multiple line segment detection. The use of multiple line segments increases the overall fault tolerance of our framework providing strong statistical support for the rectification process. The proposed framework is used for the automatic rectification, metric correction, and rotation of distorted integral images. The performance of our framework is assessed over a number of integral images with varying scene complexity and noise levels.

  9. 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.

  10. Molecular Mapping Alzheimer's Disease: MALDI Imaging of Formalin-fixed, Paraffin-embedded Human Hippocampal Tissue

    PubMed Central

    Kelley, Andrea R.; Perry, George; Bethea, Chloe; Castellani, Rudolph J.; Bach, Stephan B.H.

    2016-01-01

    A method for the molecular mapping of formalin-fixed, paraffin-embedded human hippocampal tissue affected by Alzheimer's disease (AD) is presented. This approach utilizes imaging mass spectrometry (IMS) with matrix-assisted laser desorption/ionization (MALDI). The usefulness of this technique in comparing diseased versus nor mal tissue at the molecular level while continuing to maintain topological and morphological integrity is evident in the preliminary findings. The critical correlation of the deparaffination, washing, matrix deposition, and analysis steps in handling the tissue sections and how these steps impact the successful mapping of human hippocampal tissue is clearly demonstrated. By use of this technique we have been able to identify several differences between the hippocampal AD tissue and the control hippocampal tissue. From the observed peptide clip masses we present preliminary identifications of the amyloid-beta peptides known to be prominent in the brains of those with AD. We have obtained high-resolution mass spectra and mass images with 100μm spatial resolution. Future experiments will couple this work with MALDI LIFT experiments to enable top down proteomics of fresh frozen tissue, which is not possible with paraffin-embedded tissues. PMID:27843502

  11. An integrated approach to fast and informative morphological vouchering of nematodes for applications in molecular barcoding.

    PubMed

    De Ley, Paul; De Ley, Irma Tandingan; Morris, Krystalynne; Abebe, Eyualem; Mundo-Ocampo, Manuel; Yoder, Melissa; Heras, Joseph; Waumann, Dora; Rocha-Olivares, Axayácatl; Jay Burr, A H; Baldwin, James G; Thomas, W Kelley

    2005-10-29

    Molecular surveys of meiofaunal diversity face some interesting methodological challenges when it comes to interstitial nematodes from soils and sediments. Morphology-based surveys are greatly limited in processing speed, while barcoding approaches for nematodes are hampered by difficulties of matching sequence data with traditional taxonomy. Intermediate technology is needed to bridge the gap between both approaches. An example of such technology is video capture and editing microscopy, which consists of the recording of taxonomically informative multifocal series of microscopy images as digital video clips. The integration of multifocal imaging with sequence analysis of the D2D3 region of large subunit (LSU) rDNA is illustrated here in the context of a combined morphological and barcode sequencing survey of marine nematodes from Baja California and California. The resulting video clips and sequence data are made available online in the database NemATOL (http://nematol.unh.edu/). Analyses of 37 barcoded nematodes suggest that these represent at least 32 species, none of which matches available D2D3 sequences in public databases. The recorded multifocal vouchers allowed us to identify most specimens to genus, and will be used to match specimens with subsequent species identifications and descriptions of preserved specimens. Like molecular barcodes, multifocal voucher archives are part of a wider effort at structuring and changing the process of biodiversity discovery. We argue that data-rich surveys and phylogenetic tools for analysis of barcode sequences are an essential component of the exploration of phyla with a high fraction of undiscovered species. Our methods are also directly applicable to other meiofauna such as for example gastrotrichs and tardigrades.

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

    PubMed

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

    2012-04-01

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

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

    PubMed

    Berry, Clifford R; Garg, Predeep

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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

    2015-06-01

    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.

  16. A variational path integral molecular dynamics study of a solid helium-4

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi

    2011-01-01

    In the present study, a variational path integral molecular dynamics method developed by the author [Chem. Phys. Lett. 482 (2009) 165] is applied to a solid helium-4 in the ground state. The method is a molecular dynamics algorithm for a variational path integral method which can be used to generate the exact ground state numerically. The solid state is shown to successfully be realized by the method, although a poor trial wavefunction that cannot describe the solid state is used.

  17. 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.

  18. A window on disease pathogenesis and potential therapeutic strategies: molecular imaging for arthritis

    PubMed Central

    2011-01-01

    Novel molecular imaging techniques are at the forefront of both preclinical and clinical imaging strategies. They have significant potential to offer visualisation and quantification of molecular and cellular changes in health and disease. This will help to shed light on pathobiology and underlying disease processes and provide further information about the mechanisms of action of novel therapeutic strategies. This review explores currently available molecular imaging techniques that are available for preclinical studies with a focus on optical imaging techniques and discusses how current and future advances will enable translation into the clinic for patients with arthritis. PMID:21345267

  19. Endothelial cell targeted molecular imaging in tumor angiogenesis: strategies and current status.

    PubMed

    Xu, Ye; Zeng, Yun; Liu, Yanhong; Liu, Gang; Ai, Hua

    2013-01-01

    Angiogenesis plays crucial roles in tumor growth, progression and metastasis. Non-invasive in vivo imaging of tumor neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly anti-angiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of cellular/molecular processes before gross pathological changes, leading to better understanding of fundamental biological processes of tumor angiogenesis. In this review, we will summarize recent progresses on molecular imaging of attractive biochemical epitopes in tumor angiogenesis, especially the endothelial cell targets-based imaging probes.

  20. Integration of RF-optical upconversion modules for millimeter-wave sensing and imaging systems

    NASA Astrophysics Data System (ADS)

    Yao, Peng; Shrieen, Rownak; Macario, Julien; Schuetz, Christopher A.; Prather, Dennis W.

    2011-01-01

    The integration of an opto-electronic mmW module for application to RF sensing and imaging is presented. Component integration consisting of ultra-broad band antennas, PIN switching, low noise amplifiers, and photonic phase modulator, is discussed. A fully integrated module working up to 130GHz is characterized and presented. Applications in a distributed aperture RF imaging system are discussed.

  1. 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.

  2. 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.

  3. 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

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

    PubMed Central

    Daste, Frederic

    2016-01-01

    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

  5. Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage

    NASA Astrophysics Data System (ADS)

    Wachsmann-Hogiu, Sebastian; Krakow, Deborah; Kirilova, Veneta T.; Cohn, Daniel H.; Bertolotto, Cristina; Acuna, Dora; Fang, Qiyin; Krivorov, Nikola; Farkas, Daniel L.

    2005-03-01

    It has recently been shown that mutations in Filamin A and B genes produce a large spectrum of skeletal disorders in developing fetuses. However, high-resolution optical microscopy in cartilage growth plate using fluorescent antibody assays, which should elucidate molecular aspects of these disorders, is extremely difficult due to the high level of autofluoresce in this tissue. We apply multiphoton, confocal, lifetime and spectral microscopy to (i) image and characterize autofluorophores in chondrocytes and subtract their contributions to obtain a corrected antibody-marker fluorescence signal, and (ii) measure the interaction between Filamin A and B proteins by detecting the fluorescence resonance energy transfer (FRET) between markers of the two proteins. Taking advantage of the different fluorescence spectra of the endogenous and exogenous markers, we can significantly reduce the autofluorescence background. Preliminary results of the FRET experiments suggest no interaction between Filamin A and B proteins. However, developing of new antibodies targeting the carboxy-terminal immunoglobulin-like domain may be necessary to confirm this result.

  6. Decorrelating Clutter Statistics for Long Integration Time SAR Imaging

    NASA Astrophysics Data System (ADS)

    Leanza, Antonio; Monti Guarnieri, Andrea; Recchia, Andrea; Broquetas Ibars, Antoni; Ruiz Rodon, Josep

    2015-05-01

    It is presented an experiment aimed to assess and eventually complement the Billingsley Internal Clutter Motion (ICM) model for long integration time SAR imaging. Exploiting a real-aperture rotating antenna Ground-Based RADAR, observations of rural areas in different periods of the year have been performed. The collected data, obtained from two different acquisition modes, have been processed to obtain short-term and long-term clutter de-correlation analysis. The results obtained revealed interesting aspects of the phenomenon. In particular, it can be observed that the process is non-stationary with time, say minutes to hours, and that DC/AC ratio follows a day/night characteristic. Moreover, the results showed values of the AC component decay rate β higher than the foreseen ones in the considered spectral interval, which is quite below the one analyzed in the Billingsley experiment.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis.

    PubMed

    Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S; Ng, T

    2014-06-01

    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.

  13. Ab initio path integral ring polymer molecular dynamics: Vibrational spectra of molecules

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Nakayama, Akira

    2008-01-01

    The path integral ring polymer molecular dynamics method is combined with 'on-the-fly' ab initio electronic structure calculations and applied to vibrational spectra of small molecules, LiH and H 2O, at the room temperature. The results are compared with those of the numerically exact solution and ab initio path integral centroid molecular dynamics calculation. The peak positions in the calculated spectra are found to be reasonable, showing the red-shift due to potential anharmonicity. This unification enables the investigation of real-time quantum dynamics of chemically complex molecular systems on the ab initio Born-Oppenheimer potential energy surface.

  14. Benchmark values for molecular three-center integrals arising in the Dirac equation

    NASA Astrophysics Data System (ADS)

    Baǧcı, A.; Hoggan, P. E.

    2015-10-01

    Previous papers by the authors report that they obtained compact, arbitrarily accurate expressions for two-center, one- and two-electron relativistic molecular integrals expressed over Slater-type orbitals. In the present study, accuracy limits of expressions given are examined for three-center nuclear attraction integrals, which are one-electron, three-center integrals with no analytically closed-form expression. In this work new molecular auxiliary functions are used. They are obtained via Neumann expansion of the Coulomb interaction. The numerical global adaptive method is used to evaluate these integrals for arbitrary values of orbital parameters and quantum numbers. Several methods, such as Laplace expansion of Coulomb interaction, single-center expansion, and the Fourier transformation method, have previously been used to evaluate these integrals considering the values of principal quantum numbers in the set of positive integer numbers. This study of three-center integrals places no restrictions on quantum numbers in all ranges of orbital parameters.

  15. Benchmark values for molecular three-center integrals arising in the Dirac equation.

    PubMed

    Bağcı, A; Hoggan, P E

    2015-10-01

    Previous papers by the authors report that they obtained compact, arbitrarily accurate expressions for two-center, one- and two-electron relativistic molecular integrals expressed over Slater-type orbitals. In the present study, accuracy limits of expressions given are examined for three-center nuclear attraction integrals, which are one-electron, three-center integrals with no analytically closed-form expression. In this work new molecular auxiliary functions are used. They are obtained via Neumann expansion of the Coulomb interaction. The numerical global adaptive method is used to evaluate these integrals for arbitrary values of orbital parameters and quantum numbers. Several methods, such as Laplace expansion of Coulomb interaction, single-center expansion, and the Fourier transformation method, have previously been used to evaluate these integrals considering the values of principal quantum numbers in the set of positive integer numbers. This study of three-center integrals places no restrictions on quantum numbers in all ranges of orbital parameters.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20-140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we are one of the first to present data from multi-energy photon-processing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at http://hdl.handle.net/10092/8531.

  18. 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.

  19. 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

  20. On the applicability of centroid and ring polymer path integral molecular dynamics for vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Witt, Alexander; Ivanov, Sergei D.; Shiga, Motoyuki; Forbert, Harald; Marx, Dominik

    2009-05-01

    Centroid molecular dynamics (CMD) and ring polymer molecular dynamics (RPMD) are two conceptually distinct extensions of path integral molecular dynamics that are able to generate approximate quantum dynamics of complex molecular systems. Both methods can be used to compute quasiclassical time correlation functions which have direct application in molecular spectroscopy; in particular, to infrared spectroscopy via dipole autocorrelation functions. The performance of both methods for computing vibrational spectra of several simple but representative molecular model systems is investigated systematically as a function of temperature and isotopic substitution. In this context both CMD and RPMD feature intrinsic problems which are quantified and investigated in detail. Based on the obtained results guidelines for using CMD and RPMD to compute infrared spectra of molecular systems are provided.

  1. Integral imaging microscopy with enhanced depth-of-field using a spatial multiplexing.

    PubMed

    Kwon, Ki-Chul; Erdenebat, Munkh-Uchral; Alam, Md Ashraful; Lim, Young-Tae; Kim, Kwang Gi; Kim, Nam

    2016-02-08

    A depth-of-field enhancement method for integral imaging microscopy system using a spatial multiplexing structure consisting of a beamsplitter with dual video channels and micro lens arrays is proposed. A computational integral imaging reconstruction algorithm generates two sets of depth-sliced images for the acquired depth information of the captured elemental image arrays and the well-focused depth-slices of both image sets are combined where each is focused on a different depth plane of the specimen. A prototype is implemented, and the experimental results demonstrate that the depth-of-field of the reconstructed images in the proposed integral imaging microscopy is significantly increased compared with conventional integral imaging microscopy systems.

  2. 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

  3. Molecular imaging as a guide for the treatment of central nervous system disorders.

    PubMed

    Kim, Euitae; Howes, Oliver D; Kapur, Shitij

    2013-09-01

    Molecular imaging techniques have a number of advantages for research into the pathophysiology and treatment of central nervous system (CNS) disorders. Firstly, they provide a noninvasive means of characterizing physiological processes in the living brain, enabling molecular alterations to be linked to clinical changes. Secondly, the pathophysiological target in a given CNS disorder can be measured in animal models and in experimental human models in the same way, which enables translational research. Moreover, as molecular imaging facilitates the detection of functional change which precedes gross pathology, it is particularly useful for the early diagnosis and treatment of CNS disorders. This review considers the application of molecular imaging to CNS disorders focusing on its potential to inform the development and evaluation of treatments. We focus on schizophrenia, Parkinson's disease, depression, and dementia as major CNS disorders. We also review the potential of molecular imaging to guide new drug development for CNS disorders.

  4. Molecular Strong Field Ionization viewed with Photoelectron Velocity Map Imaging

    NASA Astrophysics Data System (ADS)

    Sandor, Peter

    In this thesis, work is presented on molecular strong-field ionization, during which an electron is removed from polyatomic molecules in the presence of strong laser fields. This is a process which is the basis of a number of experimental techniques to uncover electronic dynamics in atoms and molecules on the femtosecond and attosecond timescale. 'Strong' refers to an electric field strength which leads to a response from the system which can not be modeled perturbatively. These fields can be easily produced in the focus of femtosecond laser radiation, as is done in this work. With the use of velocity map imaging of the photoelectron in coincidence with the fragment ion, multiple ionization--dissociation pathways can be distinguished. It is shown that as opposed to early attempts to model the process, multiple low-lying states are populated in the ion, and also the signatures of multielectron dynamics are revealed. By changing the laser pulse duration from 30 fs to below 10 fs, control is demonstrated over which quantum states of the ion are populated. It is also shown that for pulses shorter than 10 fs (which is a timescale below the shortest vibrational period in molecules), ionization pathways that involve motion of the nuclei are almost completely shut off. Finally, the origin of electrons with <1 meV kinetic energy is discussed. A two-step model is proposed for creating the electrons: the first step is population transfer to high-lying excited states of the neutral molecule by the laser field; the second step is ionization. Different ionization mechanisms are examined and their viability is checked against available data.

  5. 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 less

  6. Transmission imaging for integrated PET-MR systems.

    PubMed

    Bowen, Spencer L; Fuin, Niccolò; Levine, Michael A; Catana, Ciprian

    2016-08-07

    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

  7. 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

  8. 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…

  9. Molecular Integrity of Mitochondria Alters by Potassium Chloride.

    PubMed

    Mishra, Suman; Mishra, Rajnikant

    2015-01-01

    Potassium chloride (KCl) has been commonly used in homogenization buffer and procedures of protein extraction. It is known to facilitate release of membrane-associated molecules but the higher concentration of KCl may affect the integrity of mitochondria by breaching the electrostatic force between the lipids and proteins. Therefore, it has been intended to explore the effect of KCl on mitochondrial proteome. The mitochondria were isolated from the mice liver and sub-fractionated into mitochondrial matrix and outer mitochondrial membrane fraction. The fractions were analysed by denaturing polyacrylamide gel electrophoresis (PAGE) and 2D-PAGE. The analysis of ultrastructure and protein profiles by MALDI-MS and data-mining reveals KCl-associated alterations in the integrity of mitochondria and its proteome. The mitochondrial membrane, cristae, and the matrix proteins appear altered under the influence of KCl.

  10. 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

  11. Near-infrared Molecular Probes for In Vivo Imaging

    PubMed Central

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

    2012-01-01

    Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo because of the low absorption of biological molecules in this region. This Unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications. PMID:22470154

  12. Attosecond time-resolved imaging of molecular structure by photoelectron holography.

    PubMed

    Bian, Xue-Bin; Bandrauk, André D

    2012-06-29

    Dynamic imaging of the molecular structure of H(2)(+) is investigated by attosecond photoelectron holography. The interference between direct (reference) and backward rescattered (signal) photoelectrons in attosecond photoelectron holography reveals the birth time of both channels and the spatial information of molecular structure. This is confirmed by simulations with a semiclassical model and numerical solutions of the corresponding time-dependent Schrödinger equation, suggesting an attosecond time-resolved way of imaging molecular structure obtained from laser induced rescattering of ionized electrons. It is shown that both short and long rescattered electron trajectories can be imaged from the momentum distribution.

  13. Benchmark values for molecular two-electron integrals arising from the Dirac equation.

    PubMed

    Bağcı, A; Hoggan, P E

    2015-02-01

    The two-center two-electron Coulomb and hybrid integrals arising in relativistic and nonrelativistic ab initio calculations on molecules are evaluated. Compact, arbitrarily accurate expressions are obtained. They are expressed through molecular auxiliary functions and evaluated with the numerical Global-adaptive method for arbitrary values of parameters in the noninteger Slater-type orbitals. Highly accurate benchmark values are presented for these integrals. The convergence properties of new molecular auxiliary functions are investigated. The comparison for two-center two-electron integrals is made with results obtained from single center expansions by translation of the wave function to a single center with integer principal quantum numbers and results obtained from the Cuba numerical integration algorithm, respectively. The procedures discussed in this work are capable of yielding highly accurate two-center two-electron integrals for all ranges of orbital parameters.

  14. Benchmark values for molecular two-electron integrals arising from the Dirac equation

    NASA Astrophysics Data System (ADS)

    Baǧcı, A.; Hoggan, P. E.

    2015-02-01

    The two-center two-electron Coulomb and hybrid integrals arising in relativistic and nonrelativistic ab initio calculations on molecules are evaluated. Compact, arbitrarily accurate expressions are obtained. They are expressed through molecular auxiliary functions and evaluated with the numerical Global-adaptive method for arbitrary values of parameters in the noninteger Slater-type orbitals. Highly accurate benchmark values are presented for these integrals. The convergence properties of new molecular auxiliary functions are investigated. The comparison for two-center two-electron integrals is made with results obtained from single center expansions by translation of the wave function to a single center with integer principal quantum numbers and results obtained from the Cuba numerical integration algorithm, respectively. The procedures discussed in this work are capable of yielding highly accurate two-center two-electron integrals for all ranges of orbital parameters.

  15. Molecular Characterization of Pediatric Restrictive Cardiomyopathy from Integrative Genomics.

    PubMed

    Rindler, Tara N; Hinton, Robert B; Salomonis, Nathan; Ware, Stephanie M

    2017-01-18

    Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM. RNA-Seq on a cohort of pediatric RCM patients compared to other forms of adult cardiomyopathy and controls identified transcriptional differences highly common to the cardiomyopathies, as well as those unique to RCM. Transcripts selectively induced in RCM include many known and novel G-protein coupled receptors linked to calcium handling and contractile regulation. In-depth comparisons of alternative splicing revealed splicing events shared among cardiomyopathy subtypes, as well as those linked solely to RCM. Genes identified with altered alternative splicing implicate RBM20, a DCM splicing factor, as a potential mediator of alternative splicing in RCM. We present the first comprehensive report on molecular pathways dysregulated in pediatric RCM including unique/shared pathways identified compared to other cardiomyopathy subtypes and demonstrate that disruption of alternative splicing patterns in pediatric RCM occurs in the inverse direction as DCM.

  16. Molecular Characterization of Pediatric Restrictive Cardiomyopathy from Integrative Genomics

    PubMed Central

    Rindler, Tara N.; Hinton, Robert B.; Salomonis, Nathan; Ware, Stephanie M.

    2017-01-01

    Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM. RNA-Seq on a cohort of pediatric RCM patients compared to other forms of adult cardiomyopathy and controls identified transcriptional differences highly common to the cardiomyopathies, as well as those unique to RCM. Transcripts selectively induced in RCM include many known and novel G-protein coupled receptors linked to calcium handling and contractile regulation. In-depth comparisons of alternative splicing revealed splicing events shared among cardiomyopathy subtypes, as well as those linked solely to RCM. Genes identified with altered alternative splicing implicate RBM20, a DCM splicing factor, as a potential mediator of alternative splicing in RCM. We present the first comprehensive report on molecular pathways dysregulated in pediatric RCM including unique/shared pathways identified compared to other cardiomyopathy subtypes and demonstrate that disruption of alternative splicing patterns in pediatric RCM occurs in the inverse direction as DCM. PMID:28098235

  17. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    SciTech Connect

    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

    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, 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.

  18. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    DOE PAGES

    Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; ...

    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

  19. 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

  20. Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems

    NASA Astrophysics Data System (ADS)

    Kamibayashi, Yuki; Miura, Shinichi

    2016-08-01

    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.

  1. 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.

  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.

  3. Communication: Kirkwood-Buff integrals in the thermodynamic limit from small-sized molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Cortes-Huerto, R.; Kremer, K.; Potestio, R.

    2016-10-01

    We present an accurate and efficient method to obtain Kirkwood-Buff (KB) integrals in the thermodynamic limit from small-sized molecular dynamics simulations. By introducing finite size effects into integral equations of statistical mechanics, we derive an analytical expression connecting the KB integrals of the bulk system with the fluctuations of the number of molecules in the corresponding closed system. We validate the method by calculating the activity coefficients of aqueous urea mixtures and the KB integrals of Lennard-Jones fluids. Moreover, our results demonstrate how to identify simulation conditions under which computer simulations reach the thermodynamic limit.

  4. 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

  5. Imaging the Temporal Evolution of Molecular Orbitals during Ultrafast Dissociation

    NASA Astrophysics Data System (ADS)

    Sann, H.; Havermeier, T.; Müller, C.; Kim, H.-K.; Trinter, F.; Waitz, M.; Voigtsberger, J.; Sturm, F.; Bauer, T.; Wallauer, R.; Schneider, D.; Weller, M.; Goihl, C.; Tross, J.; Cole, K.; Wu, J.; Schöffler, M. S.; Schmidt-Böcking, H.; Jahnke, T.; Simon, M.; Dörner, R.

    2016-12-01

    We investigate the temporal evolution of molecular frame angular distributions of Auger electrons emitted during ultrafast dissociation of HCl following a resonant single-photon excitation. The electron emission pattern changes its shape from that of a molecular σ orbital to that of an atomic p state as the system evolves from a molecule into two separated atoms.

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

    PubMed

    Blower, Phil

    2006-04-14

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

  7. 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…

  8. Schemes for Integrating Text and Image in the Science Textbook: Effects on Comprehension and Situational Interest

    ERIC Educational Resources Information Center

    Peterson, Matthew O.

    2016-01-01

    Science education researchers have turned their attention to the use of images in textbooks, both because pages are heavily illustrated and because visual literacy is an important aptitude for science students. Text-image integration in the textbook is described here as composition schemes in increasing degrees of integration: prose primary (PP),…

  9. Ab initio centroid path integral molecular dynamics: Application to vibrational dynamics of diatomic molecular systems

    NASA Astrophysics Data System (ADS)

    Ohta, Yasuhito; Ohta, Koji; Kinugawa, Kenichi

    2004-01-01

    An ab initio centroid molecular dynamics (CMD) method is developed by combining the CMD method with the ab initio molecular orbital method. The ab initio CMD method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For the H2 molecule, the temperature dependence of the peak frequency of the vibrational spectral density is investigated. The results are compared with those obtained by the ab initio classical molecular dynamics method and exact quantum mechanical treatment. It is shown that the vibrational frequency obtained from the ab initio CMD approaches the exact first excitation frequency as the temperature lowers. For the HF molecule, the position autocorrelation function is also analyzed in detail. The present CMD method is shown to well reproduce the exact quantum result for the information on the vibrational properties of the system.

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

    PubMed Central

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

    2016-01-01

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

  11. Attenuation correction in molecular fluorescence imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yang, Bin; Tunnell, James W.

    2016-03-01

    Fluorescence-guided surgery has demonstrated more complete tumor resections in both preclinical models and clinical applications. However, intraoperative fluorescence-based imaging can be challenging due to attenuation of the fluorescence by intrinsic tissue scattering and absorption. Removing attenuation in fluorescence imaging is critical in many applications. We have developed both a model based approach and an experimental approach to retrieve attenuation corrected fluorescence based on spatial frequency domain imaging (SFDI). In the model based approach, we extended an attenuation correction model initially developed for point measurement into wide-field imaging with SFDI. To achieve attenuation correction, tissue optical properties were evaluated at both excitation and emission wavelengths, which were later applied in the model. In an in-vitro phantom study, we achieved a relative flat intensity profile over entire absorption range compared to over 80% drop at the highest absorption level before correction. Similar performance was also observed in an ex-vivo tissue study. However, lengthy image acquisition and image processing make this method ideal for static imaging instead of video-rate imaging. To achieve video-rate correction, we developed an experimental approach to reduce absorption by limiting the imaging depth using a high spatial frequency pattern. The absorption reduced fluorescence image was obtained by performing a simple demodulation. The in-vitro phantom study suggested an approximate 20% intensity drop at the highest absorption level compared to over 70% intensity drop before correction. This approach enabled video-rate attenuation corrected imaging at 19 fps, making this technique viable for clinical image guided surgery.

  12. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    DTIC Science & Technology

    2010-07-01

    or core needle biopsy to surgical resection. To allow examination of suspect lesions, a variety of endoscopic imaging techniques may be employed...in Barrett’s esophagus : a novel, low-cost endoscopic microscope,” Gastrointestinal Endoscopy 68, 737-744 (2008). 11. T. J. Muldoon, N. Thekkek, D...video rate microscopic imaging (Project 1) will be used to examine the margin region itself with contrast provided by the use of targeted imaging

  13. Molecular imaging of stem cells for the treatment of acute myocardial infarction

    PubMed Central

    Li, Xiao; Wang, Yi-Ning; Jin, Zheng-Yu

    2015-01-01

    Stem cell therapy has a unique potential and promises hope for the treatment of acute myocardial infarction. Preclinical studies have identified barriers to clinical translation, one of which involves the monitoring of transplanted cells and the elucidation of their fates in vivo. Molecular imaging may help the solutions for these challenges. In this review, we illustrate the mechanisms by which molecular imaging enables insights into and the development of stem cell therapy. PMID:26309546

  14. Integrated Development of Serum Molecular Markers for Early Diagnosis of Breast Cancer

    DTIC Science & Technology

    2006-09-01

    Molecular Makers for Early Diagnosis of Breast Cancer PRINCIPAL INVESTIGATOR: Anna Lokshin, Ph.D. CONTRACTING ORGANIZATION: University of...NUMBER Integrated Development of Serum Molecular Makers for Early Diagnosis of Breast Cancer 5b. GRANT NUMBER DAMD17-03-1-0696 5c. PROGRAM...Therefore, studies at this stage involve screening people and lead to diagnosis and treatment. The aims of this phase include assessment of (i) the

  15. 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

  16. Ixodes ventalloi: morphological and molecular support for species integrity.

    PubMed

    Latrofa, Maria Stefania; Giannelli, Alessio; Persichetti, Maria Flaminia; Pennisi, Maria Grazia; Solano-Gallego, Laia; Brianti, Emanuele; Parisi, Antonio; Wall, Richard; Dantas-Torres, Filipe; Otranto, Domenico

    2017-01-01

    Despite their medical and veterinary importance, some tick species are so poorly studied, that their role within pathogen vector transmission cycles is difficult to assess. The tick Ixodes ventalloi is one such species, and its biology and phylogenetic status remain an issue of debate. In the present study, specimens of adult I. ventalloi (n = 65 females; n = 31 males) infesting cats in the Lipari Island (Aeolian archipelago, Sicily, southern Italy) were characterized morphologically and molecularly, the latter based on mitochondrial 16S rRNA and cytochrome c oxidase subunit 1 (cox1) genes. The genetic data and phylogenetic analyses for both mitochondrial genes suggest the existence of two distinct genogroups. The ecological and epidemiological significance of the genetic structure within the I. ventalloi endemic population remains to be determined. The results highlight the need for further analysis of this tick species, including whole mitochondrial genome sequencing and crossbreeding studies, which will be pivotal to complement features of its status as a vector of pathogens.

  17. 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.

  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. Algorithms and novel applications based on the isokinetic ensemble. I. Biophysical and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Minary, Peter; Martyna, Glenn J.; Tuckerman, Mark E.

    2003-02-01

    In this paper (Paper I) and a companion paper (Paper II), novel new algorithms and applications of the isokinetic ensemble as generated by Gauss' principle of least constraint, pioneered for use with molecular dynamics 20 years ago, are presented for biophysical, path integral, and Car-Parrinello based ab initio molecular dynamics. In Paper I, a new "extended system" version of the isokinetic equations of motion that overcomes the ergodicity problems inherent in the standard approach, is developed using a new theory of non-Hamiltonian phase space analysis [M. E. Tuckerman et al., Europhys. Lett. 45, 149 (1999); J. Chem. Phys. 115, 1678 (2001)]. Reversible multiple time step integrations schemes for the isokinetic methods, first presented by Zhang [J. Chem. Phys. 106, 6102 (1997)] are reviewed. Next, holonomic constraints are incorporated into the isokinetic methodology for use in fast efficient biomolecular simulation studies. Model and realistic examples are presented in order to evaluate, critically, the performance of the new isokinetic molecular dynamic schemes. Comparisons are made to the, now standard, canonical dynamics method, Nosé-Hoover chain dynamics [G. J. Martyna et al., J. Chem. Phys. 97, 2635 (1992)]. The new isokinetic techniques are found to yield more efficient sampling than the Nosé-Hoover chain method in both path integral molecular dynamics and biophysical molecular dynamics calculations. In Paper II, the use of isokinetic methods in Car-Parrinello based ab initio molecular dynamics calculations is presented.

  20. Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities

    PubMed Central

    Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B.

    2017-01-01

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities. PMID:28096716