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Sample records for quantitative molecular imaging

  1. Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics.

    Science.gov (United States)

    Kaneda, Megan M; Caruthers, Shelton; Lanza, Gregory M; Wickline, Samuel A

    2009-10-01

    A broad array of nanomaterials is available for use as contrast agents for molecular imaging and drug delivery. Due to the lack of endogenous background signal in vivo and the high NMR sensitivity of the (19)F atom, liquid perfluorocarbon nanoemulsions make ideal agents for cellular and magnetic resonance molecular imaging. The perfluorocarbon core material is surrounded by a lipid monolayer which can be functionalized with a variety of agents including targeting ligands, imaging agents and drugs either individually or in combination. Multiple copies of targeting ligands (approximately 20-40 monoclonal antibodies or 200-400 small molecule ligands) serve to enhance avidity through multivalent interactions while the composition of the particle's perfluorocarbon core results in high local concentrations of (19)F. Additionally, lipophilic drugs contained within molecularly targeted nanoemulsions can result in contact facilitated drug delivery to target cells. Ultimately, the dual use of perfluorocarbon nanoparticles for both site targeted drug delivery and molecular imaging may provide both imaging of disease states as well as conclusive evidence that drug delivery is localized to the area of interest. This review will focus on liquid perfluorocarbon nanoparticles as (19)F molecular imaging agents and for targeted drug delivery in cancer and cardiovascular disease.

  2. Photoacoustic molecular imaging for in vivo liver iron quantitation

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2015-07-01

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

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

    Science.gov (United States)

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

    2016-05-05

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

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

    Science.gov (United States)

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

    2016-05-01

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

  6. Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging

    Science.gov (United States)

    Yang, Chenying; Hou, Vivian W.; Girard, Emily J.; Nelson, Leonard Y.; Seibel, Eric J.

    2014-07-01

    Fluorescence molecular imaging with exogenous probes improves specificity for the detection of diseased tissues by targeting unambiguous molecular signatures. Additionally, increased diagnostic sensitivity is expected with the application of multiple molecular probes. We developed a real-time multispectral fluorescence-reflectance scanning fiber endoscope (SFE) for wide-field molecular imaging of fluorescent dye-labeled molecular probes at nanomolar detection levels. Concurrent multichannel imaging with the wide-field SFE also allows for real-time mitigation of the background autofluorescence (AF) signal, especially when fluorescein, a U.S. Food and Drug Administration approved dye, is used as the target fluorophore. Quantitative tissue AF was measured for the ex vivo porcine esophagus and murine brain tissues across the visible and near-infrared spectra. AF signals were then transferred to the unit of targeted fluorophore concentration to evaluate the SFE detection sensitivity for sodium fluorescein and cyanine. Next, we demonstrated a real-time AF mitigation algorithm on a tissue phantom, which featured molecular probe targeted cells of high-grade dysplasia on a substrate containing AF species. The target-to-background ratio was enhanced by more than one order of magnitude when applying the real-time AF mitigation algorithm. Furthermore, a quantitative estimate of the fluorescein photodegradation (photobleaching) rate was evaluated and shown to be insignificant under the illumination conditions of SFE. In summary, the multichannel laser-based flexible SFE has demonstrated the capability to provide sufficient detection sensitivity, image contrast, and quantitative target intensity information for detecting small precancerous lesions in vivo.

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

    Science.gov (United States)

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

    2016-03-01

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

  8. Quantitative Imaging of Molecular Order in Lipid Membranes Using Two-Photon Fluorescence Polarimetry

    Science.gov (United States)

    Gasecka, Alicja; Han, Tsai-Jung; Favard, Cyril; Cho, Bong Rae; Brasselet, Sophie

    2009-01-01

    Abstract We present a polarimetric two-photon microscopy technique to quantitatively image the local static molecular orientational behavior in lipid and cell membranes. This approach, based on a tunable excitation polarization state complemented by a polarized readout, is easily implementable and does not require hypotheses on the molecular angular distribution such as its mean orientation, which is a main limitation in traditional fluorescence anisotropy measurements. The method is applied to the investigation of the molecular angular distribution in giant unilamellar vesicles formed by liquid-ordered and liquid-disordered micro-domains, and in COS-7 cell membranes. The highest order contrast between ordered and disordered domains is obtained for dyes locating within the membrane acyl chains. PMID:19917241

  9. Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging

    Science.gov (United States)

    Gao, Liang; Hammoudi, Ahmad A.; Li, Fuhai; Thrall, Michael J.; Cagle, Philip T.; Chen, Yuanxin; Yang, Jian; Xia, Xiaofeng; Fan, Yubo; Massoud, Yehia; Wang, Zhiyong; Wong, Stephen T. C.

    2012-06-01

    The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.

  10. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent.

    Science.gov (United States)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-21

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  11. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    Science.gov (United States)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  12. Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging.

    Science.gov (United States)

    Yang, Yaliang; Li, Fuhai; Gao, Liang; Wang, Zhiyong; Thrall, Michael J; Shen, Steven S; Wong, Kelvin K; Wong, Stephen T C

    2011-08-01

    We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.

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

    Science.gov (United States)

    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.

  14. [Molecular imaging].

    Science.gov (United States)

    Turetschek, K; Wunderbaldinger, P

    2002-01-01

    The disclosure of the human genoma, the progress in understanding of diseases on molecular and cellular levels, the discovery of new disease-specific targets, and the development of new medications will revolutionize our understanding of the etiology and the treatment of many disease entities. Radiologists are faced with a paradigm shift from unspecific to specific molecular imaging techniques as well as with enormous speed in the development of new methods and should be enrolled actively in this field of medicine.

  15. Quantitative imaging as cancer biomarker

    Science.gov (United States)

    Mankoff, David A.

    2015-03-01

    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  16. Quantitative imaging methods in osteoporosis.

    Science.gov (United States)

    Oei, Ling; Koromani, Fjorda; Rivadeneira, Fernando; Zillikens, M Carola; Oei, Edwin H G

    2016-12-01

    Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray absorptiometry (DXA) are among the strongest known predictors of future osteoporotic fractures. Therefore, current clinical decision making relies heavily on accurate assessment of these imaging features. Further, novel quantitative techniques are being developed to appraise additional characteristics of osteoporosis including three-dimensional bone architecture with quantitative computed tomography (QCT). Dedicated high-resolution (HR) CT equipment is available to enhance image quality. At the other end of the spectrum, by utilizing post-processing techniques such as the trabecular bone score (TBS) information on three-dimensional architecture can be derived from DXA images. Further developments in magnetic resonance imaging (MRI) seem promising to not only capture bone micro-architecture but also characterize processes at the molecular level. This review provides an overview of various quantitative imaging techniques based on different radiological modalities utilized in clinical osteoporosis care and research.

  17. Quantitative Hyperspectral Reflectance Imaging

    Directory of Open Access Journals (Sweden)

    Ted A.G. Steemers

    2008-09-01

    Full Text Available Hyperspectral imaging is a non-destructive optical analysis technique that can for instance be used to obtain information from cultural heritage objects unavailable with conventional colour or multi-spectral photography. This technique can be used to distinguish and recognize materials, to enhance the visibility of faint or obscured features, to detect signs of degradation and study the effect of environmental conditions on the object. We describe the basic concept, working principles, construction and performance of a laboratory instrument specifically developed for the analysis of historical documents. The instrument measures calibrated spectral reflectance images at 70 wavelengths ranging from 365 to 1100 nm (near-ultraviolet, visible and near-infrared. By using a wavelength tunable narrow-bandwidth light-source, the light energy used to illuminate the measured object is minimal, so that any light-induced degradation can be excluded. Basic analysis of the hyperspectral data includes a qualitative comparison of the spectral images and the extraction of quantitative data such as mean spectral reflectance curves and statistical information from user-defined regions-of-interest. More sophisticated mathematical feature extraction and classification techniques can be used to map areas on the document, where different types of ink had been applied or where one ink shows various degrees of degradation. The developed quantitative hyperspectral imager is currently in use by the Nationaal Archief (National Archives of The Netherlands to study degradation effects of artificial samples and original documents, exposed in their permanent exhibition area or stored in their deposit rooms.

  18. Quantitative luminescence imaging system

    Science.gov (United States)

    Batishko, C. R.; Stahl, K. A.; Fecht, B. A.

    The goal of the Measurement of Chemiluminescence project is to develop and deliver a suite of imaging radiometric instruments for measuring spatial distributions of chemiluminescence. Envisioned deliverables include instruments working at the microscopic, macroscopic, and life-sized scales. Both laboratory and field portable instruments are envisioned. The project also includes development of phantoms as enclosures for the diazoluminomelanin (DALM) chemiluminescent chemistry. A suite of either phantoms in a variety of typical poses, or phantoms that could be adjusted to a variety of poses, is envisioned. These are to include small mammals (rats), mid-sized mammals (monkeys), and human body parts. A complete human phantom that can be posed is a long-term goal of the development. Taken together, the chemistry and instrumentation provide a means for imaging rf dosimetry based on chemiluminescence induced by the heat resulting from rf energy absorption. The first delivered instrument, the Quantitative Luminescence Imaging System (QLIS), resulted in a patent, and an R&D Magazine 1991 R&D 100 award, recognizing it as one of the 100 most significant technological developments of 1991. The current status of the project is that three systems have been delivered, several related studies have been conducted, two preliminary human hand phantoms have been delivered, system upgrades have been implemented, and calibrations have been maintained. Current development includes sensitivity improvements to the microscope-based system; extension of the large-scale (potentially life-sized targets) system to field portable applications; extension of the 2-D large-scale system to 3-D measurement; imminent delivery of a more refined human hand phantom and a rat phantom; rf, thermal and imaging subsystem integration; and continued calibration and upgrade support.

  19. Quantitative imaging with fluorescent biosensors.

    Science.gov (United States)

    Okumoto, Sakiko; Jones, Alexander; Frommer, Wolf B

    2012-01-01

    Molecular activities are highly dynamic and can occur locally in subcellular domains or compartments. Neighboring cells in the same tissue can exist in different states. Therefore, quantitative information on the cellular and subcellular dynamics of ions, signaling molecules, and metabolites is critical for functional understanding of organisms. Mass spectrometry is generally used for monitoring ions and metabolites; however, its temporal and spatial resolution are limited. Fluorescent proteins have revolutionized many areas of biology-e.g., fluorescent proteins can report on gene expression or protein localization in real time-yet promoter-based reporters are often slow to report physiologically relevant changes such as calcium oscillations. Therefore, novel tools are required that can be deployed in specific cells and targeted to subcellular compartments in order to quantify target molecule dynamics directly. We require tools that can measure enzyme activities, protein dynamics, and biophysical processes (e.g., membrane potential or molecular tension) with subcellular resolution. Today, we have an extensive suite of tools at our disposal to address these challenges, including translocation sensors, fluorescence-intensity sensors, and Förster resonance energy transfer sensors. This review summarizes sensor design principles, provides a database of sensors for more than 70 different analytes/processes, and gives examples of applications in quantitative live cell imaging.

  20. Quantitative imaging of atomic and molecular species in cancer cell cultures with TOF-SIMS and Laser-SNMS

    Energy Technology Data Exchange (ETDEWEB)

    Fartmann, M.; Kriegeskotte, C.; Dambach, S.; Wittig, A.; Sauerwein, W.; Arlinghaus, H.F

    2004-06-15

    For boron neutron capture therapy, a promising cancer therapy under development, knowledge about the subcellular boron distribution is important. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and nonresonant laser secondary neutral mass spectrometry (NR-Laser-SNMS) have been used for examining freeze-fractured, freeze-dried human melanoma cells incubated with sodium mercaptoundecahydro-closo-dodecaborate (Na{sub 2}{sup 10}B{sub 12}H{sub 11}SH,BSH), a {sup 10}B containing drug. With both techniques, elemental and molecular images were obtained from the cancer cells with very high sensitivity and subcellular resolution. The measurement of the K/Na ratio demonstrated that the preparation technique used was appropriate for preserving the chemical and structural integrity of living cells. The boron images showed that the intensity of intracellular and extracellular boron signals was clearly different after incubation of cells in different boron concentrations.

  1. Quantitative Imaging in Cancer Clinical Trials.

    Science.gov (United States)

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  2. Quantitative ultrasonic phased array imaging

    Science.gov (United States)

    Engle, Brady J.; Schmerr, Lester W., Jr.; Sedov, Alexander

    2014-02-01

    When imaging with ultrasonic phased arrays, what do we actually image? What quantitative information is contained in the image? Ad-hoc delay-and-sum methods such as the synthetic aperture focusing technique (SAFT) and the total focusing method (TFM) fail to answer these questions. We have shown that a new quantitative approach allows the formation of flaw images by explicitly inverting the Thompson-Gray measurement model. To examine the above questions, we have set up a software simulation test bed that considers a 2-D scalar scattering problem of a cylindrical inclusion with the method of separation of variables. It is shown that in SAFT types of imaging the only part of the flaw properly imaged is the front surface specular response of the flaw. Other responses (back surface reflections, creeping waves, etc.) are improperly imaged and form artifacts in the image. In the case of TFM-like imaging the quantity being properly imaged is an angular integration of the front surface reflectivity. The other, improperly imaged responses are also averaged, leading to a reduction in some of the artifacts present. Our results have strong implications for flaw sizing and flaw characterization with delay-and-sum images.

  3. Quantitative multiphoton imaging

    Science.gov (United States)

    König, Karsten; Weinigel, Martin; Breunig, Hans Georg; Uchugonova, Aisada

    2014-02-01

    Certified clinical multiphoton tomographs for label-free multidimensional high-resolution in vivo imaging have been introduced to the market several years ago. Novel tomographs include a flexible 360° scan head attached to a mechanooptical arm for autofluorescence and SHG imaging as well as a CARS module. Non-fluorescent lipids and water, mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen can be imaged in vivo with submicron resolution in human skin. Sensitive and rapid detectors allow single photon counting and the construction of 3D maps where the number of detected photons per voxel is depicted. Intratissue concentration profiles from endogenous as well exogenous substances can be generated when the number of detected photons can be correlated with the number of molecules with respect to binding and scattering behavior. Furthermore, the skin ageing index SAAID based on the ratio elastin/collagen as well as the epidermis depth based on the onset of SHG generation can be determined.

  4. Quantitative phase imaging of arthropods

    Science.gov (United States)

    Sridharan, Shamira; Katz, Aron; Soto-Adames, Felipe; Popescu, Gabriel

    2015-01-01

    Abstract. Classification of arthropods is performed by characterization of fine features such as setae and cuticles. An unstained whole arthropod specimen mounted on a slide can be preserved for many decades, but is difficult to study since current methods require sample manipulation or tedious image processing. Spatial light interference microscopy (SLIM) is a quantitative phase imaging (QPI) technique that is an add-on module to a commercial phase contrast microscope. We use SLIM to image a whole organism springtail Ceratophysella denticulata mounted on a slide. This is the first time, to our knowledge, that an entire organism has been imaged using QPI. We also demonstrate the ability of SLIM to image fine structures in addition to providing quantitative data that cannot be obtained by traditional bright field microscopy. PMID:26334858

  5. Quantitative ultrasound in cancer imaging.

    Science.gov (United States)

    Feleppa, Ernest J; Mamou, Jonathan; Porter, Christopher R; Machi, Junji

    2011-02-01

    Ultrasound is a relatively inexpensive, portable, and versatile imaging modality that has a broad range of clinical uses. It incorporates many imaging modes, such as conventional gray-scale "B-mode" imaging to display echo amplitude in a scanned plane; M-mode imaging to track motion at a given fixed location over time; duplex, color, and power Doppler imaging to display motion in a scanned plane; harmonic imaging to display nonlinear responses to incident ultrasound; elastographic imaging to display relative tissue stiffness; and contrast-agent imaging with simple contrast agents to display blood-filled spaces or with targeted agents to display specific agent-binding tissue types. These imaging modes have been well described in the scientific, engineering, and clinical literature. A less well-known ultrasonic imaging technology is based on quantitative ultrasound (QUS), which analyzes the distribution of power as a function of frequency in the original received echo signals from tissue and exploits the resulting spectral parameters to characterize and distinguish among tissues. This article discusses the attributes of QUS-based methods for imaging cancers and providing improved means of detecting and assessing tumors. The discussion will include applications to imaging primary prostate cancer and metastatic cancer in lymph nodes to illustrate the methods. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Quantitative imaging of turbulent and reacting flows

    Energy Technology Data Exchange (ETDEWEB)

    Paul, P.H. [Sandia National Laboratories, Livermore, CA (United States)

    1993-12-01

    Quantitative digital imaging, using planar laser light scattering techniques is being developed for the analysis of turbulent and reacting flows. Quantitative image data, implying both a direct relation to flowfield variables as well as sufficient signal and spatial dynamic range, can be readily processed to yield two-dimensional distributions of flowfield scalars and in turn two-dimensional images of gradients and turbulence scales. Much of the development of imaging techniques to date has concentrated on understanding the requisite molecular spectroscopy and collision dynamics to be able to determine how flowfield variable information is encoded into the measured signal. From this standpoint the image is seen as a collection of single point measurements. The present effort aims at realizing necessary improvements in signal and spatial dynamic range, signal-to-noise ratio and spatial resolution in the imaging system as well as developing excitation/detection strategies which provide for a quantitative measure of particular flowfield scalars. The standard camera used for the study is an intensified CCD array operated in a conventional video format. The design of the system was based on detailed modeling of signal and image transfer properties of fast UV imaging lenses, image intensifiers and CCD detector arrays. While this system is suitable for direct scalar imaging, derived quantities (e.g. temperature or velocity images) require an exceptionally wide dynamic range imaging detector. To apply these diagnostics to reacting flows also requires a very fast shuttered camera. The authors have developed and successfully tested a new type of gated low-light level detector. This system relies on fast switching of proximity focused image-diode which is direct fiber-optic coupled to a cooled CCD array. Tests on this new detector show significant improvements in detection limit, dynamic range and spatial resolution as compared to microchannel plate intensified arrays.

  7. GPC and quantitative phase imaging

    DEFF Research Database (Denmark)

    Palima, Darwin; Banas, Andrew Rafael; Villangca, Mark Jayson

    2016-01-01

    shaper followed by the potential of GPC for biomedical and multispectral applications where we experimentally demonstrate the active light shaping of a supercontinuum laser over most of the visible wavelength range. Finally, we discuss how GPC can be advantageously applied for Quantitative Phase Imaging...

  8. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

  9. Quantitative imaging features: extension of the oncology medical image database

    Science.gov (United States)

    Patel, M. N.; Looney, P. T.; Young, K. C.; Halling-Brown, M. D.

    2015-03-01

    Radiological imaging is fundamental within the healthcare industry and has become routinely adopted for diagnosis, disease monitoring and treatment planning. With the advent of digital imaging modalities and the rapid growth in both diagnostic and therapeutic imaging, the ability to be able to harness this large influx of data is of paramount importance. The Oncology Medical Image Database (OMI-DB) was created to provide a centralized, fully annotated dataset for research. The database contains both processed and unprocessed images, associated data, and annotations and where applicable expert determined ground truths describing features of interest. Medical imaging provides the ability to detect and localize many changes that are important to determine whether a disease is present or a therapy is effective by depicting alterations in anatomic, physiologic, biochemical or molecular processes. Quantitative imaging features are sensitive, specific, accurate and reproducible imaging measures of these changes. Here, we describe an extension to the OMI-DB whereby a range of imaging features and descriptors are pre-calculated using a high throughput approach. The ability to calculate multiple imaging features and data from the acquired images would be valuable and facilitate further research applications investigating detection, prognosis, and classification. The resultant data store contains more than 10 million quantitative features as well as features derived from CAD predictions. Theses data can be used to build predictive models to aid image classification, treatment response assessment as well as to identify prognostic imaging biomarkers.

  10. [Molecular diagnostics and imaging].

    Science.gov (United States)

    Fink, Christian; Fisseler-Eckhoff, Annette; Huss, Ralf; Nestle, Ursula

    2009-01-01

    Molecular diagnostic methods and biological imaging techniques can make a major contribution to tailoring patients' treatment needs with regard to medical, ethical and pharmaco-economic aspects. Modern diagnostic methods are already being used to help identify different sub-groups of patients with thoracic tumours who are most likely to benefit significantly from a particular type of treatment. This contribution looks at the most recent developments that have been made in the field of thoracic tumour diagnosis and analyses the pros and cons of new molecular and other imaging techniques in day-to-day clinical practice.

  11. Quantitative histogram analysis of images

    Science.gov (United States)

    Holub, Oliver; Ferreira, Sérgio T.

    2006-11-01

    loading of an image No. of bits in a word: 32 No. of processors used: 1 Has the code been vectorized or parallelized?: No No of lines in distributed program, including test data, etc.:138 946 No. of bytes in distributed program, including test data, etc.:15 166 675 Distribution format: tar.gz Nature of physical problem: Quantification of image data (e.g., for discrimination of molecular species in gels or fluorescent molecular probes in cell cultures) requires proprietary or complex software packages, which might not include the relevant statistical parameters or make the analysis of multiple images a tedious procedure for the general user. Method of solution: Tool for conversion of RGB bitmap image into luminance-linear image and extraction of luminance histogram, probability distribution, and statistical parameters (average brightness, standard deviation, variance, minimal and maximal brightness, mode, skewness and kurtosis of histogram and median of probability distribution) with possible selection of region of interest (ROI) and lower and upper threshold levels. Restrictions on the complexity of the problem: Does not incorporate application-specific functions (e.g., morphometric analysis) Typical running time: Seconds (depending on image size and processor speed) Unusual features of the program: None

  12. Molecular imaging: current status and emerging strategies

    Energy Technology Data Exchange (ETDEWEB)

    Pysz, M.A. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Gambhir, S.S. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Departments of Bioengineering and Materials Science and Engineering, Stanford University, Stanford, CA (United States); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States)

    2010-07-15

    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 treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (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 multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) 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 US imaging with molecularly-targeted microbubbles are attractive strategies as 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 US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  13. Molecular imaging of melanin distribution in vivo and quantitative differential diagnosis of human pigmented lesions using label-free harmonic generation biopsy (Conference Presentation)

    Science.gov (United States)

    Sun, Chi-Kuang; Wei, Ming-Liang; Su, Yu-Hsiang; Weng, Wei-Hung; Liao, Yi-Hua

    2017-02-01

    Harmonic generation microscopy is a noninvasive repetitive imaging technique that provides real-time 3D microscopic images of human skin with a sub-femtoliter resolution and high penetration down to the reticular dermis. In this talk, we show that with a strong resonance effect, the third-harmonic-generation (THG) modality provides enhanced contrast on melanin and allows not only differential diagnosis of various pigmented skin lesions but also quantitative imaging for longterm tracking. This unique capability makes THG microscopy the only label-free technique capable of identifying the active melanocytes in human skin and to image their different dendriticity patterns. In this talk, we will review our recent efforts to in vivo image melanin distribution and quantitatively diagnose pigmented skin lesions using label-free harmonic generation biopsy. This talk will first cover the spectroscopic study on the melanin enhanced THG effect in human cells and the calibration strategy inside human skin for quantitative imaging. We will then review our recent clinical trials including: differential diagnosis capability study on pigmented skin tumors; as well as quantitative virtual biopsy study on pre- and post- treatment evaluation on melasma and solar lentigo. Our study indicates the unmatched capability of harmonic generation microscopy to perform virtual biopsy for noninvasive histopathological diagnosis of various pigmented skin tumors, as well as its unsurpassed capability to noninvasively reveal the pathological origin of different hyperpigmentary diseases on human face as well as to monitor the efficacy of laser depigmentation treatments. This work is sponsored by National Health Research Institutes.

  14. Molecular imaging I

    Energy Technology Data Exchange (ETDEWEB)

    Semmler, Wolfhard [Deutsches Krebsforschungszentrum, Heidelberg (DE). Abt. fuer Medizinische Physik in der Radiologie (E020) Forschungsschwerpunkt Innovative Krebsdiagnostik und -therapie (E); Schwaiger, Markus (eds.) [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    2008-07-01

    The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

  15. Molecular imaging II

    Energy Technology Data Exchange (ETDEWEB)

    Semmler, Wolfhard [Deutsches Krebsforschungszentrum, Heidelberg (DE). Abt. fuer Medizinische Physik in der Radiologie (E020) Forschungsschwerpunkt Innovative Krebsdiagnostik und -therapie (E); Schwaiger, Markus (eds.) [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    2008-07-01

    The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

  16. Quantitative analysis of qualitative images

    Science.gov (United States)

    Hockney, David; Falco, Charles M.

    2005-03-01

    We show optical evidence that demonstrates artists as early as Jan van Eyck and Robert Campin (c1425) used optical projections as aids for producing their paintings. We also have found optical evidence within works by later artists, including Bermejo (c1475), Lotto (c1525), Caravaggio (c1600), de la Tour (c1650), Chardin (c1750) and Ingres (c1825), demonstrating a continuum in the use of optical projections by artists, along with an evolution in the sophistication of that use. However, even for paintings where we have been able to extract unambiguous, quantitative evidence of the direct use of optical projections for producing certain of the features, this does not mean that paintings are effectively photographs. Because the hand and mind of the artist are intimately involved in the creation process, understanding these complex images requires more than can be obtained from only applying the equations of geometrical optics.

  17. GPC and quantitative phase imaging

    Science.gov (United States)

    Palima, Darwin; Bañas, Andrew Rafael; Villangca, Mark Jayson; Glückstad, Jesper

    2016-03-01

    Generalized Phase Contrast (GPC) is a light efficient method for generating speckle-free contiguous optical distributions using binary-only or analog phase levels. It has been used in applications such as optical trapping and manipulation, active microscopy, structured illumination, optical security, parallel laser marking and labelling and recently in contemporary biophotonics applications such as for adaptive and parallel two-photon optogenetics and neurophotonics. We will present our most recent GPC developments geared towards these applications. We first show a very compact static light shaper followed by the potential of GPC for biomedical and multispectral applications where we experimentally demonstrate the active light shaping of a supercontinuum laser over most of the visible wavelength range. Finally, we discuss how GPC can be advantageously applied for Quantitative Phase Imaging (QPI).

  18. Molecular Imaging of the Kidneys

    Science.gov (United States)

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

    2010-01-01

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

  19. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

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

  20. Molecular Biomedical Imaging Laboratory (MBIL)

    Data.gov (United States)

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

  1. Molecular nuclear cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soo; Paeng, Jin Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2004-04-01

    Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

  2. Quantitative photoacoustic imaging of nanoparticles in cells and tissues.

    Science.gov (United States)

    Cook, Jason R; Frey, Wolfgang; Emelianov, Stanislav

    2013-02-26

    Quantitative visualization of nanoparticles in cells and tissues, while preserving the spatial information, is very challenging. A photoacoustic imaging technique to depict the presence and quantity of nanoparticles is presented. This technique is based on the dependence of the photoacoustic signal on both the nanoparticle quantity and the laser fluence. Quantitative photoacoustic imaging is a robust technique that does not require knowledge of the local fluence, but a relative change in the fluence. This eliminates the need for sophisticated methods or models to determine the energy distribution of light in turbid media. Quantitative photoacoustic imaging was first applied to nanoparticle-loaded cells, and quantitation was validated by inductively coupled plasma mass spectrometry. Quantitative photoacoustic imaging was then extended to xenograft tumor tissue sections, and excellent agreement with traditional histopathological analysis was demonstrated. Our results suggest that quantitative photoacoustic imaging may be used in many applications including the determination of the efficiency and effectiveness of molecular targeting strategies for cell studies and animal models, the quantitative assessment of photoacoustic contrast agent biodistribution, and the validation of in vivo photoacoustic imaging.

  3. Molecular imaging applications for immunology.

    Science.gov (United States)

    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.

  4. Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features.

    Science.gov (United States)

    Gevaert, Olivier; Mitchell, Lex A; Achrol, Achal S; Xu, Jiajing; Echegaray, Sebastian; Steinberg, Gary K; Cheshier, Samuel H; Napel, Sandy; Zaharchuk, Greg; Plevritis, Sylvia K

    2014-10-01

    To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these features with various molecular data. Clinical, molecular, and MR imaging data for GBMs in 55 patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive after local ethics committee and institutional review board approval. Regions of interest (ROIs) corresponding to enhancing necrotic portions of tumor and peritumoral edema were drawn, and quantitative image features were derived from these ROIs. Robust quantitative image features were defined on the basis of an intraclass correlation coefficient of 0.6 for a digital algorithmic modification and a test-retest analysis. The robust features were visualized by using hierarchic clustering and were correlated with survival by using Cox proportional hazards modeling. Next, these robust image features were correlated with manual radiologist annotations from the Visually Accessible Rembrandt Images (VASARI) feature set and GBM molecular subgroups by using nonparametric statistical tests. A bioinformatic algorithm was used to create gene expression modules, defined as a set of coexpressed genes together with a multivariate model of cancer driver genes predictive of the module's expression pattern. Modules were correlated with robust image features by using the Spearman correlation test to create radiogenomic maps and to link robust image features with molecular pathways. Eighteen image features passed the robustness analysis and were further analyzed for the three types of ROIs, for a total of 54 image features. Three enhancement features were significantly correlated with survival, 77 significant correlations were found between robust quantitative features and the VASARI feature set, and seven image features were correlated with molecular subgroups (P < .05 for all). A radiogenomics map was

  5. Molecular imaging with fast beams

    Energy Technology Data Exchange (ETDEWEB)

    Heber, O. [Weizmann Inst. of Science, Rehovoth (Israel). Dept. of Particle Physics; Zajfman, D. [Weizmann Inst. of Science, Rehovoth (Israel). Dept. of Particle Physics; Kella, D. [Weizmann Inst. of Science, Rehovoth (Israel). Dept. of Particle Physics; Vager, Z. [Weizmann Inst. of Science, Rehovoth (Israel). Dept. of Particle Physics; Watson, R.L. [Cyclotron Institute, Texas A and M University, College Station, Texas 77843 (United States); Horvat, V. [Cyclotron Institute, Texas A and M University, College Station, Texas 77843 (United States)

    1995-05-01

    Three dimensional imaging of the molecular dissociation process in fast collisions is presented with two different setups. One setup is for a fast molecular beam from an accelerator colliding with a gas target. The second setup is for a molecular target system and the collision process is with highly ionized fast beam. The advantages of each system are discussed. The three dimensional imaging of the molecular fragments is done with special detectors that combine the CCD image with time of flight data. An example of the molecular beam measurement is given for an 11 MeV B{sub 2} beam. (orig.).

  6. Molecular photoacoustic imaging

    OpenAIRE

    Frogh Jafarian Dehkordi; Ali Mahmoud Pashazadeh; Majid Assadi

    2015-01-01

    Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods...

  7. Molecular imaging in Alzheimer's disease.

    Science.gov (United States)

    Lascola, Christopher

    2005-11-01

    Molecular imaging represents a new term for a long-standing quest to image cellular and molecular processes in vivo. The development of a successful molecular imaging approach starts with a well-defined diagnostic question best answered using in vivo imaging. A selective target for a particular disease state is then identified and a biocompatible probe selective for that target is developed. Many of the challenges of finding selective disease targets and probes that bind selectively to those targets in vivo are evident in the 25-year history of molecular imaging in Alzheimer's disease. This article provides a brief overview of molecular imaging in Alzheimer's disease and its potential for early diagnosis and treatment development.

  8. White-light Quantitative Phase Imaging Unit

    CERN Document Server

    Baek, YoonSeok; Yoon, Jonghee; Kim, Kyoohyun; Park, YongKeun

    2016-01-01

    We introduce the white light quantitative phase imaging unit (WQPIU) as a practical realization of quantitative phase imaging (QPI) on standard microscope platforms. The WQPIU is a compact stand-alone unit which measures sample induced phase delay under white-light illumination. It does not require any modification of the microscope or additional accessories for its use. The principle of the WQPIU based on lateral shearing interferometry and phase shifting interferometry provides a cost-effective and user-friendly use of QPI. The validity and capacity of the presented method are demonstrated by measuring quantitative phase images of polystyrene beads, human red blood cells, HeLa cells and mouse white blood cells. With speckle-free imaging capability due to the use of white-light illumination, the WQPIU is expected to expand the scope of QPI in biological sciences as a powerful but simple imaging tool.

  9. Cancer detection by quantitative fluorescence image analysis.

    Science.gov (United States)

    Parry, W L; Hemstreet, G P

    1988-02-01

    Quantitative fluorescence image analysis is a rapidly evolving biophysical cytochemical technology with the potential for multiple clinical and basic research applications. We report the application of this technique for bladder cancer detection and discuss its potential usefulness as an adjunct to methods used currently by urologists for the diagnosis and management of bladder cancer. Quantitative fluorescence image analysis is a cytological method that incorporates 2 diagnostic techniques, quantitation of nuclear deoxyribonucleic acid and morphometric analysis, in a single semiautomated system to facilitate the identification of rare events, that is individual cancer cells. When compared to routine cytopathology for detection of bladder cancer in symptomatic patients, quantitative fluorescence image analysis demonstrated greater sensitivity (76 versus 33 per cent) for the detection of low grade transitional cell carcinoma. The specificity of quantitative fluorescence image analysis in a small control group was 94 per cent and with the manual method for quantitation of absolute nuclear fluorescence intensity in the screening of high risk asymptomatic subjects the specificity was 96.7 per cent. The more familiar flow cytometry is another fluorescence technique for measurement of nuclear deoxyribonucleic acid. However, rather than identifying individual cancer cells, flow cytometry identifies cellular pattern distributions, that is the ratio of normal to abnormal cells. Numerous studies by others have shown that flow cytometry is a sensitive method to monitor patients with diagnosed urological disease. Based upon results in separate quantitative fluorescence image analysis and flow cytometry studies, it appears that these 2 fluorescence techniques may be complementary tools for urological screening, diagnosis and management, and that they also may be useful separately or in combination to elucidate the oncogenic process, determine the biological potential of tumors

  10. Time-resolved molecular imaging

    Science.gov (United States)

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

    2016-06-01

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

  11. Tumor Molecular Imaging with Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhen Cheng

    2016-03-01

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

  12. Molecular photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Frogh Jafarian Dehkordi

    2015-04-01

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

  13. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  14. Quantitative Measurements using Ultrasound Vector Flow Imaging

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt

    2016-01-01

    Duplex Vector Flow Imaging (VFI) imaging is introduced as a replacement for spectral Doppler, as it automatically can yield fully quantitative flow estimates without angle correction. Continuous VFI data over 9 s for 10 pulse cycles were acquired by a 3 MHz convex probe connected to the SARUS......L/stroke (true: 1.15 mL/stroke, bias: 12.2%). Measurements down to 160 mm were obtained with a relative standard deviation and bias of less than 10% for the lateral component for stationary, parabolic flow. The method can, thus, find quantitative velocities, angles, and volume flows at sites currently...

  15. Advances in multimodal molecular imaging.

    Science.gov (United States)

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

    2017-03-01

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

  16. Quantitative Imaging with a Mobile Phone Microscope

    Science.gov (United States)

    Skandarajah, Arunan; Reber, Clay D.; Switz, Neil A.; Fletcher, Daniel A.

    2014-01-01

    Use of optical imaging for medical and scientific applications requires accurate quantification of features such as object size, color, and brightness. High pixel density cameras available on modern mobile phones have made photography simple and convenient for consumer applications; however, the camera hardware and software that enables this simplicity can present a barrier to accurate quantification of image data. This issue is exacerbated by automated settings, proprietary image processing algorithms, rapid phone evolution, and the diversity of manufacturers. If mobile phone cameras are to live up to their potential to increase access to healthcare in low-resource settings, limitations of mobile phone–based imaging must be fully understood and addressed with procedures that minimize their effects on image quantification. Here we focus on microscopic optical imaging using a custom mobile phone microscope that is compatible with phones from multiple manufacturers. We demonstrate that quantitative microscopy with micron-scale spatial resolution can be carried out with multiple phones and that image linearity, distortion, and color can be corrected as needed. Using all versions of the iPhone and a selection of Android phones released between 2007 and 2012, we show that phones with greater than 5 MP are capable of nearly diffraction-limited resolution over a broad range of magnifications, including those relevant for single cell imaging. We find that automatic focus, exposure, and color gain standard on mobile phones can degrade image resolution and reduce accuracy of color capture if uncorrected, and we devise procedures to avoid these barriers to quantitative imaging. By accommodating the differences between mobile phone cameras and the scientific cameras, mobile phone microscopes can be reliably used to increase access to quantitative imaging for a variety of medical and scientific applications. PMID:24824072

  17. Quantitative imaging with a mobile phone microscope.

    Directory of Open Access Journals (Sweden)

    Arunan Skandarajah

    Full Text Available Use of optical imaging for medical and scientific applications requires accurate quantification of features such as object size, color, and brightness. High pixel density cameras available on modern mobile phones have made photography simple and convenient for consumer applications; however, the camera hardware and software that enables this simplicity can present a barrier to accurate quantification of image data. This issue is exacerbated by automated settings, proprietary image processing algorithms, rapid phone evolution, and the diversity of manufacturers. If mobile phone cameras are to live up to their potential to increase access to healthcare in low-resource settings, limitations of mobile phone-based imaging must be fully understood and addressed with procedures that minimize their effects on image quantification. Here we focus on microscopic optical imaging using a custom mobile phone microscope that is compatible with phones from multiple manufacturers. We demonstrate that quantitative microscopy with micron-scale spatial resolution can be carried out with multiple phones and that image linearity, distortion, and color can be corrected as needed. Using all versions of the iPhone and a selection of Android phones released between 2007 and 2012, we show that phones with greater than 5 MP are capable of nearly diffraction-limited resolution over a broad range of magnifications, including those relevant for single cell imaging. We find that automatic focus, exposure, and color gain standard on mobile phones can degrade image resolution and reduce accuracy of color capture if uncorrected, and we devise procedures to avoid these barriers to quantitative imaging. By accommodating the differences between mobile phone cameras and the scientific cameras, mobile phone microscopes can be reliably used to increase access to quantitative imaging for a variety of medical and scientific applications.

  18. Quantitative imaging of bilirubin by photoacoustic microscopy

    Science.gov (United States)

    Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

    2013-03-01

    Noninvasive detection of both bilirubin concentration and its distribution is important for disease diagnosis. Here we implemented photoacoustic microscopy (PAM) to detect bilirubin distribution. We first demonstrate that our PAM system can measure the absorption spectra of bilirubin and blood. We also image bilirubin distributions in tissuemimicking samples, both without and with blood mixed. Our results show that PAM has the potential to quantitatively image bilirubin in vivo for clinical applications.

  19. Quantitative image processing in fluid mechanics

    Science.gov (United States)

    Hesselink, Lambertus; Helman, James; Ning, Paul

    1992-01-01

    The current status of digital image processing in fluid flow research is reviewed. In particular, attention is given to a comprehensive approach to the extraction of quantitative data from multivariate databases and examples of recent developments. The discussion covers numerical simulations and experiments, data processing, generation and dissemination of knowledge, traditional image processing, hybrid processing, fluid flow vector field topology, and isosurface analysis using Marching Cubes.

  20. Molecular Imaging of Ovarian Cancer

    OpenAIRE

    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 rece...

  1. Quantitative Techniques in PET-CT Imaging

    NARCIS (Netherlands)

    Basu, Sandip; Zaidi, Habib; Holm, Soren; Alavi, Abass

    2011-01-01

    The appearance of hybrid PET/CT scanners has made quantitative whole body scanning of radioactive tracers feasible. This paper deals with the novel concepts for assessing global organ function and disease activity based on combined functional (PET) and structural (CT or MR) imaging techniques, their

  2. In Vivo Imaging of Molecularly Targeted Phage

    Directory of Open Access Journals (Sweden)

    Kimberly A. Kelly

    2006-12-01

    Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

  3. Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer.

    Science.gov (United States)

    Zheng, Hong-Mei; Chen, Chuang; Wu, Xin-Hong; Chen, Jian; Sun, Si; Sun, Jin-Zhong; Wang, Ming-Wei; Sun, Sheng-Rong

    2016-02-01

    Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with high heterogeneity and poor prognosis. Currently, the treatment effect of TNBC has reached a bottleneck, rendering new breakthroughs difficult. Cancer invasion is not an entirely cell-autonomous process, requiring the cells to transmigrate across the surrounding extracellular matrix (ECM) barriers. Developing a new system that integrates key constituents in the tumor microenvironment with pivotal cancer cell molecules is essential for the in-depth investigation of the mechanism of invasion in TNBC. We describe a computer-aided algorithm developed using quantum dot (QD)-based multiplex molecular imaging of TNBC tissues. We performed in situ simultaneous imaging and quantitative detection of epidermal growth factor receptor (EGFR), expressed in the TNBC cell membrane, and collagen IV, the major ECM constituent; calculated the EGFR/collagen IV ratio; and investigated the prognostic value of the EGFR/collagen IV ratio in TNBC. We simultaneously imaged and quantitatively detected EGFR and collagen IV in the TNBC samples. In all patients, quantitative determination showed a statistically significant negative correlation between EGFR and collagen IV. The 5-year disease-free survival (5-DFS) of the high and low EGFR/collagen IV ratio subgroups was significantly different. The EGFR/collagen IV ratio was predictive and was an independent prognostic indicator in TNBC. Compared with EGFR expression, the EGFR/collagen IV ratio had a greater prognostic value for 5-DFS. Our findings open up a new avenue for predicting the clinical outcome in TNBC from the perspective of integrating molecules expressed in both cancer cells and the ECM.

  4. Molecular imaging with terahertz waves.

    Science.gov (United States)

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

    2011-02-28

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

  5. Metrology Standards for Quantitative Imaging Biomarkers.

    Science.gov (United States)

    Sullivan, Daniel C; Obuchowski, Nancy A; Kessler, Larry G; Raunig, David L; Gatsonis, Constantine; Huang, Erich P; Kondratovich, Marina; McShane, Lisa M; Reeves, Anthony P; Barboriak, Daniel P; Guimaraes, Alexander R; Wahl, Richard L

    2015-12-01

    Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies.

  6. Quantitative image analysis of celiac disease.

    Science.gov (United States)

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2015-03-07

    We outline the use of quantitative techniques that are currently used for analysis of celiac disease. Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy. It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients. New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested. It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients.

  7. Quantitative image analysis of celiac disease

    Science.gov (United States)

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2015-01-01

    We outline the use of quantitative techniques that are currently used for analysis of celiac disease. Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy. It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients. New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested. It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients. PMID:25759524

  8. Dose reduction in molecular breast imaging

    Science.gov (United States)

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

    2011-10-01

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

  9. Quantitative magnetic resonance micro-imaging methods for pharmaceutical research.

    Science.gov (United States)

    Mantle, M D

    2011-09-30

    The use of magnetic resonance imaging (MRI) as a tool in pharmaceutical research is now well established and the current literature covers a multitude of different pharmaceutically relevant research areas. This review focuses on the use of quantitative magnetic resonance micro-imaging techniques and how they have been exploited to extract information that is of direct relevance to the pharmaceutical industry. The article is divided into two main areas. The first half outlines the theoretical aspects of magnetic resonance and deals with basic magnetic resonance theory, the effects of nuclear spin-lattice (T(1)), spin-spin (T(2)) relaxation and molecular diffusion upon image quantitation, and discusses the applications of rapid magnetic resonance imaging techniques. In addition to the theory, the review aims to provide some practical guidelines for the pharmaceutical researcher with an interest in MRI as to which MRI pulse sequences/protocols should be used and when. The second half of the article reviews the recent advances and developments that have appeared in the literature concerning the use of quantitative micro-imaging methods to pharmaceutically relevant research. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Molecular imaging. Fundamentals and applications

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

  11. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

    NARCIS (Netherlands)

    Esposito, Alessandro

    2006-01-01

    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These tec

  12. Quantitative Analysis in Nuclear Medicine Imaging

    CERN Document Server

    2006-01-01

    This book provides a review of image analysis techniques as they are applied in the field of diagnostic and therapeutic nuclear medicine. Driven in part by the remarkable increase in computing power and its ready and inexpensive availability, this is a relatively new yet rapidly expanding field. Likewise, although the use of radionuclides for diagnosis and therapy has origins dating back almost to the discovery of natural radioactivity itself, radionuclide therapy and, in particular, targeted radionuclide therapy has only recently emerged as a promising approach for therapy of cancer and, to a lesser extent, other diseases. As effort has, therefore, been made to place the reviews provided in this book in a broader context. The effort to do this is reflected by the inclusion of introductory chapters that address basic principles of nuclear medicine imaging, followed by overview of issues that are closely related to quantitative nuclear imaging and its potential role in diagnostic and therapeutic applications. ...

  13. Molecular imaging in cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-15

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

  14. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

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

  15. Treatment assessment of radiotherapy using MR functional quantitative imaging

    Institute of Scientific and Technical Information of China (English)

    Zheng; Chang; Chunhao; Wang

    2015-01-01

    Recent developments in magnetic resonance(MR) functional quantitative imaging have made it a potentially powerful tool to assess treatment response in radiation therapy. With its abilities to capture functional information on underlying tissue characteristics, MR functional quantitative imaging can be valuable in assessing treatment response and as such to optimize therapeutic outcome. Various MR quantitative imaging techniques, including diffusion weighted imaging, diffusion tensor imaging, MR spectroscopy and dynamic contrastenhanced imaging, have been investigated and found useful for assessment of radiotherapy. However, various aspects including data reproducibility, interpretation of biomarkers, image quality and data analysis impose challenges on applications of MR functional quantitative imaging in radiotherapy assessment. All of these challenging issues shall be addressed to help us understand whether MR functional quantitative imaging is truly beneficial and contributes to future development of radiotherapy. It is evident that individualized therapy is the future direction of patient care. MR functional quantitative imaging might serves as an indispensable tool towards this promising direction.

  16. Quantitative phase imaging through scattering media

    Science.gov (United States)

    Kollárová, Vera; Colláková, Jana; Dostál, Zbynek; Slabý, Tomas; Veselý, Pavel; Chmelík, Radim

    2015-03-01

    Coherence-controlled holographic microscope (CCHM) is an off-axis holographic system. It enables observation of a sample and its quantitative phase imaging with coherent as well as with incoherent illumination. The spatial and temporal coherence can be modified and thus also the quality and type of the image information. The coherent illumination provides numerical refocusing in wide depth range similarly to a classic coherent-light digital holographic microscopy (HM). Incoherent-light HM is characterized by a high quality, coherence-noise-free imaging with up to twice higher resolution compared to coherent illumination. Owing to an independent, free of sample reference arm of the CCHM the low spatial light coherence induces coherence-gating effect. This makes possible to observe specimen also through scattering media. We have described theoretically and simulated numerically imaging of a two dimensional object through a scattering layer by CCHM using the linear systems theory. We have investigated both strongly and weakly scattering media characterized by different amount of ballistic and diffuse light. The influence of a scattering layer on the quality of a phase signal is discussed for both types of the scattering media. A strong dependence of the imaging process on the light coherence is demonstrated. The theoretical calculations and numerical simulations are supported by experimental data gained with model samples, as well as real biologic objects particularly then by time-lapse observations of live cells reactions to substances producing optically turbid emulsion.

  17. Siderophores for molecular imaging applications.

    Science.gov (United States)

    Petrik, Milos; Zhai, Chuangyan; Haas, Hubertus; Decristoforo, Clemens

    2017-01-01

    This review covers publications on siderophores applied for molecular imaging applications, mainly for radionuclide-based imaging. Siderophores are low molecular weight chelators produced by bacteria and fungi to scavenge essential iron. Research on these molecules has a continuing history over the past 50 years. Many biomedical applications have been developed, most prominently the use of the siderophore desferrioxamine (DFO) to tackle iron overload related diseases. Recent research described the upregulation of siderophore production and transport systems during infection. Replacing iron in siderophores by radionuclides, the most prominent Ga-68 for PET, opens approaches for targeted imaging of infection; the proof of principle has been reported for fungal infections using (68)Ga-triacetylfusarinine C (TAFC). Additionally, fluorescent siderophores and therapeutic conjugates have been described and may be translated to optical imaging and theranostic applications. Siderophores have also been applied as bifunctional chelators, initially DFO as chelator for Ga-67 and more recently for Zr-89 where it has become the standard chelator in Immuno-PET. Improved DFO constructs and bifunctional chelators based on cyclic siderophores have recently been developed for Ga-68 and Zr-89 and show promising properties for radiopharmaceutical development in PET. A huge potential from basic biomedical research on siderophores still awaits to be utilized for clinical and translational imaging.

  18. Molecular Imaging of Pituitary Pathology.

    Science.gov (United States)

    de Herder, Wouter W

    2016-01-01

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

  19. Quantitative color analysis for capillaroscopy image segmentation.

    Science.gov (United States)

    Goffredo, Michela; Schmid, Maurizio; Conforto, Silvia; Amorosi, Beatrice; D'Alessio, Tommaso; Palma, Claudio

    2012-06-01

    This communication introduces a novel approach for quantitatively evaluating the role of color space decomposition in digital nailfold capillaroscopy analysis. It is clinically recognized that any alterations of the capillary pattern, at the periungual skin region, are directly related to dermatologic and rheumatic diseases. The proposed algorithm for the segmentation of digital capillaroscopy images is optimized with respect to the choice of the color space and the contrast variation. Since the color space is a critical factor for segmenting low-contrast images, an exhaustive comparison between different color channels is conducted and a novel color channel combination is presented. Results from images of 15 healthy subjects are compared with annotated data, i.e. selected images approved by clinicians. By comparison, a set of figures of merit, which highlights the algorithm capability to correctly segment capillaries, their shape and their number, is extracted. Experimental tests depict that the optimized procedure for capillaries segmentation, based on a novel color channel combination, presents values of average accuracy higher than 0.8, and extracts capillaries whose shape and granularity are acceptable. The obtained results are particularly encouraging for future developments on the classification of capillary patterns with respect to dermatologic and rheumatic diseases.

  20. Advances in multimodality molecular imaging

    Directory of Open Access Journals (Sweden)

    Zaidi Habib

    2009-01-01

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

  1. Sparse image reconstruction for molecular imaging

    CERN Document Server

    Ting, Michael; Hero, Alfred O

    2008-01-01

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

  2. Towards a quantitative OCT image analysis.

    Directory of Open Access Journals (Sweden)

    Marina Garcia Garrido

    Full Text Available Optical coherence tomography (OCT is an invaluable diagnostic tool for the detection and follow-up of retinal pathology in patients and experimental disease models. However, as morphological structures and layering in health as well as their alterations in disease are complex, segmentation procedures have not yet reached a satisfactory level of performance. Therefore, raw images and qualitative data are commonly used in clinical and scientific reports. Here, we assess the value of OCT reflectivity profiles as a basis for a quantitative characterization of the retinal status in a cross-species comparative study.Spectral-Domain Optical Coherence Tomography (OCT, confocal Scanning-Laser Ophthalmoscopy (SLO, and Fluorescein Angiography (FA were performed in mice (Mus musculus, gerbils (Gerbillus perpadillus, and cynomolgus monkeys (Macaca fascicularis using the Heidelberg Engineering Spectralis system, and additional SLOs and FAs were obtained with the HRA I (same manufacturer. Reflectivity profiles were extracted from 8-bit greyscale OCT images using the ImageJ software package (http://rsb.info.nih.gov/ij/.Reflectivity profiles obtained from OCT scans of all three animal species correlated well with ex vivo histomorphometric data. Each of the retinal layers showed a typical pattern that varied in relative size and degree of reflectivity across species. In general, plexiform layers showed a higher level of reflectivity than nuclear layers. A comparison of reflectivity profiles from specialized retinal regions (e.g. visual streak in gerbils, fovea in non-human primates with respective regions of human retina revealed multiple similarities. In a model of Retinitis Pigmentosa (RP, the value of reflectivity profiles for the follow-up of therapeutic interventions was demonstrated.OCT reflectivity profiles provide a detailed, quantitative description of retinal layers and structures including specialized retinal regions. Our results highlight the

  3. Molecular Imaging System for Monitoring Tumor Angiogenesis

    Science.gov (United States)

    Aytac, Esra; Burcin Unlu, Mehmet

    2012-02-01

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

  4. Quantitative imaging of coronary blood flow

    Directory of Open Access Journals (Sweden)

    Adam M. Alessio

    2010-04-01

    Full Text Available Adam M. Alessio received his PhD in Electrical Engineering from the University of Notre Dame in 2003. During his graduate studies he developed tomographic reconstruction methods for correlated data and helped construct a high-resolution PET system. He is currently a Research Assistant Professor in Radiology at the University of Washington. His research interests focus on improved data processing and reconstruction algorithms for PET/CT systems with an emphasis on quantitative imaging. Erik Butterworth recieved the BA degree in Mathematics from the University of Chicago in 1977. Between 1977 and 1987 he worked as a computer programmer/analyst for several small commercial software firms. Since 1988, he has worked as a software engineer on various research projects at the University of Washington. Between 1988 and 1993 he developed a real-time data aquisition for the analysis of estuarine sediment transport in the department of Geophysics. Between 1988 and 2002 he developed I4, a system for the display and analysis of cardic PET images in the department of Cardiology. Since 1993 he has worked on physiological simulation systems (XSIM from 1993 to 1999, JSim since 1999 at the National Simulation Resource Facility in Cirulatory Mass Transport and Exchange, in the Department of Bioengineering. His research interests include simulation systems and medical imaging. James H. Caldwell, MD, University of Missouri-Columbia 1970, is Professor of Medicine (Cardiology and Radiology and Adjunct Professor of Bioengineering at the University of Washington School of Medicine and Acting Head, Division of Cardiology and Director of Nuclear Cardiology for the University of Washington Hospitals, Seattle WA, USA. James B. Bassingthwaighte, MD, Toronto 1955, PhD Mayo Grad Sch Med 1964, was Professor of Physiology and of Medicine at Mayo Clinic until 1975 when he moved to the University of Washington to chair Bioengineering. He is Professor of Bioengineering and

  5. Quantitative bioluminescence imaging of mouse tumor models.

    Science.gov (United States)

    Tseng, Jen-Chieh; Kung, Andrew L

    2015-01-05

    Bioluminescence imaging (BLI) has become an essential technique for preclinical evaluation of anticancer therapeutics and provides sensitive and quantitative measurements of tumor burden in experimental cancer models. For light generation, a vector encoding firefly luciferase is introduced into human cancer cells that are grown as tumor xenografts in immunocompromised hosts, and the enzyme substrate luciferin is injected into the host. Alternatively, the reporter gene can be expressed in genetically engineered mouse models to determine the onset and progression of disease. In addition to expression of an ectopic luciferase enzyme, bioluminescence requires oxygen and ATP, thus only viable luciferase-expressing cells or tissues are capable of producing bioluminescence signals. Here, we summarize a BLI protocol that takes advantage of advances in hardware, especially the cooled charge-coupled device camera, to enable detection of bioluminescence in living animals with high sensitivity and a large dynamic range.

  6. Molecular imaging of prostate cancer.

    Science.gov (United States)

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

    2012-07-01

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

  7. Molecular Imaging with Activatable Reporter Systems

    Directory of Open Access Journals (Sweden)

    Gang Niu, Xiaoyuan Chen

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  9. Molecular Imaging of Huntington's Disease.

    Science.gov (United States)

    Ciarmiello, Andrea; Giovacchini, Giampiero; Giovannini, Elisabetta; Lazzeri, Patrizia; Borsò, Elisa; Mannironi, Antonio; Mansi, Luigi

    2017-08-01

    The onset and the clinical progression of Huntington Disease (HD) is influenced by several events prompted by a genetic mutation that affects several organs tissues including different regions of the brain. In the last decades years, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) helped to deepen the knowledge of neurodegenerative mechanisms that guide to clinical symptoms. Brain imaging with PET represents a tool to investigate the physiopathology occurring in the brain and it has been used to predict the age of onset of the disease and to evaluate the therapeutic efficacy of new drugs. This article reviews the contribution of PET and MRI in the research field on Huntington's disease, focusing in particular on some most relevant achievements that have helped recognize the molecular changes, the clinical symptoms and evolution of the disease. J. Cell. Physiol. 232: 1988-1993, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

    Science.gov (United States)

    Esposito, Alessandro

    2006-05-01

    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

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

    Science.gov (United States)

    Belkić, Dzevad; Belkić, Karen

    2013-11-01

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

  12. Quantitative phase imaging using hard x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Nugent, K.A.; Paganin, D.; Barnea, Z. [Melbourne Univ., Parkville, VIC (Australia). School of Physics; Cookson, D. F. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Gureyev, T.E. [Melbourne Univ., Parkville, VIC (Australia). School of Physics]|[CSIRO, Clayton, VIC (Australia). Div. of Forestry and Forest Products

    1997-06-01

    The quantitative imaging of a phase object using 16 keV x-rays is reported. The theoretical basis of the techniques is presented along with its implementation using a synchrotron x-ray source. It is found that the phase image is in quantitative agreement with independent measurements of the object. 13 refs., 5 figs.

  13. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  14. Molecular imaging and sensing using plasmonic nanoparticles

    Science.gov (United States)

    Crow, Matthew James

    Noble metal nanoparticles exhibit unique optical properties that are beneficial to a variety of applications, including molecular imaging. The large scattering cross sections of nanoparticles provide high contrast necessary for biomarkers. Unlike alternative contrast agents, nanoparticles provide refractive index sensitivity revealing information regarding the local cellular environment. Altering the shape and composition of the nanoparticle shifts the peak resonant wavelength of scattered light, allowing for implementation of multiple spectrally distinct tags. In this project, nanoparticles that scatter in different spectral windows are functionalized with various antibodies recognizing extra-cellular receptors integral to cancer progression. A hyperspectral imaging system is developed, allowing for visualization and spectral characterization of cells labeled with these conjugates. Various molecular imaging and microspectroscopy applications of plasmonic nanoparticles are then investigated. First, anti-EGFR gold nanospheres are shown to quantitatively measure receptor expression with similar performance to fluorescence assays. Second, anti-EGFR gold nanorods and novel anti-IGF-1R silver nanospheres are implemented to indicate local cellular refractive indices. Third, because biosensing capabilities of nanoparticle tags may be limited by plasmonic coupling, polarization mapping is investigated as a method to discern these effects. Fourth, plasmonic coupling is tested to monitor HER-2 dimerization. Experiments reveal the interparticle conformation of proximal HER-2 bound labels, required for plasmonic coupling-enhanced dielectric sensing. Fifth, all three functionalized plasmonic tags are implemented simultaneously to indicate clinically relevant cell immunophenotype information and changes in the cellular dielectric environment. Finally, flow cytometry experiments are conducted utilizing the anti-EGFR nanorod tag to demonstrate profiling of receptor expression

  15. Quantitative photoacoustic image reconstruction improves accuracy in deep tissue structures.

    Science.gov (United States)

    Mastanduno, Michael A; Gambhir, Sanjiv S

    2016-10-01

    Photoacoustic imaging (PAI) is emerging as a potentially powerful imaging tool with multiple applications. Image reconstruction for PAI has been relatively limited because of limited or no modeling of light delivery to deep tissues. This work demonstrates a numerical approach to quantitative photoacoustic image reconstruction that minimizes depth and spectrally derived artifacts. We present the first time-domain quantitative photoacoustic image reconstruction algorithm that models optical sources through acoustic data to create quantitative images of absorption coefficients. We demonstrate quantitative accuracy of less than 5% error in large 3 cm diameter 2D geometries with multiple targets and within 22% error in the largest size quantitative photoacoustic studies to date (6cm diameter). We extend the algorithm to spectral data, reconstructing 6 varying chromophores to within 17% of the true values. This quantitiative PA tomography method was able to improve considerably on filtered-back projection from the standpoint of image quality, absolute, and relative quantification in all our simulation geometries. We characterize the effects of time step size, initial guess, and source configuration on final accuracy. This work could help to generate accurate quantitative images from both endogenous absorbers and exogenous photoacoustic dyes in both preclinical and clinical work, thereby increasing the information content obtained especially from deep-tissue photoacoustic imaging studies.

  16. Inorganic Nanoparticles for Multimodal Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Swierczewska

    2011-01-01

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

  17. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

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

  18. A quantitative analysis of IRAS maps of molecular clouds

    Science.gov (United States)

    Wiseman, Jennifer J.; Adams, Fred C.

    1994-01-01

    We present an analysis of IRAS maps of five molecular clouds: Orion, Ophiuchus, Perseus, Taurus, and Lupus. For the classification and description of these astrophysical maps, we use a newly developed technique which considers all maps of a given type to be elements of a pseudometric space. For each physical characteristic of interest, this formal system assigns a distance function (a pseudometric) to the space of all maps: this procedure allows us to measure quantitatively the difference between any two maps and to order the space of all maps. We thus obtain a quantitative classification scheme for molecular clouds. In this present study we use the IRAS continuum maps at 100 and 60 micrometer(s) to produce column density (or optical depth) maps for the five molecular cloud regions given above. For this sample of clouds, we compute the 'output' functions which measure the distribution of density, the distribution of topological components, the self-gravity, and the filamentary nature of the clouds. The results of this work provide a quantitative description of the structure in these molecular cloud regions. We then order the clouds according to the overall environmental 'complexity' of these star-forming regions. Finally, we compare our results with the observed populations of young stellar objects in these clouds and discuss the possible environmental effects on the star-formation process. Our results are consistent with the recently stated conjecture that more massive stars tend to form in more 'complex' environments.

  19. Cholangiocarcinoma: Correlation between Molecular Profiling and Imaging Phenotypes.

    Directory of Open Access Journals (Sweden)

    Eran Sadot

    Full Text Available To investigate associations between imaging features of cholangiocarcinoma by visual assessment and texture analysis, which quantifies heterogeneity in tumor enhancement patterns, with molecular profiles based on hypoxia markers.The institutional review board approved this HIPAA-compliant retrospective study of CT images of intrahepatic cholangiocarcinoma, obtained before surgery. Immunostaining for hypoxia markers (EGFR, VEGF, CD24, P53, MDM2, MRP-1, HIF-1α, CA-IX, and GLUT1 was performed on pre-treatment liver biopsies. Quantitative imaging phenotypes were determined by texture analysis with gray level co-occurrence matrixes. The correlations between quantitative imaging phenotypes, qualitative imaging features (measured by radiographic inspection alone, and expression levels of the hypoxia markers from the 25 tumors were assessed.Twenty-five patients were included with a median age of 62 years (range: 54-84. The median tumor size was 10.2 cm (range: 4-14, 10 (40% were single tumors, and 90% were moderately differentiated. Positive immunostaining was recorded for VEGF in 67% of the cases, EGFR in 75%, and CD24 in 55%. On multiple linear regression analysis, quantitative imaging phenotypes correlated significantly with EGFR and VEGF expression levels (R2 = 0.4, p<0.05 and R2 = 0.2, p<0.05, respectively, while a trend was demonstrated with CD24 expression (R2 = 0.33, p = 0.1. Three qualitative imaging features correlated with VEGF and CD24 expression (P<0.05, however, none of the qualitative features correlated with the quantitative imaging phenotypes.Quantitative imaging phenotypes, as defined by texture analysis, correlated with expression of specific markers of hypoxia, regardless of conventional imaging features.

  20. Ultrafast quantitative time-stretch imaging flow cytometry of phytoplankton

    Science.gov (United States)

    Lai, Queenie T. K.; Lau, Andy K. S.; Tang, Anson H. L.; Wong, Kenneth K. Y.; Tsia, Kevin K.

    2016-03-01

    Comprehensive quantification of phytoplankton abundance, sizes and other parameters, e.g. biomasses, has been an important, yet daunting task in aquatic sciences and biofuel research. It is primarily because of the lack of effective tool to image and thus accurately profile individual microalgae in a large population. The phytoplankton species are highly diversified and heterogeneous in terms of their sizes and the richness in morphological complexity. This fact makes time-stretch imaging, a new ultrafast real-time optical imaging technology, particularly suitable for ultralarge-scale taxonomic classification of phytoplankton together with quantitative image recognition and analysis. We here demonstrate quantitative imaging flow cytometry of single phytoplankton based on quantitative asymmetric-detection time-stretch optical microscopy (Q-ATOM) - a new time-stretch imaging modality for label-free quantitative phase imaging without interferometric implementations. Sharing the similar concept of Schlieren imaging, Q-ATOM accesses multiple phase-gradient contrasts of each single phytoplankton, from which the quantitative phase profile is computed. We employ such system to capture, at an imaging line-scan rate of 11.6 MHz, high-resolution images of two phytoplankton populations (scenedesmus and chlamydomonas) in ultrafast microfluidic flow (3 m/s). We further perform quantitative taxonomic screening analysis enabled by this technique. More importantly, the system can also generate quantitative phase images of single phytoplankton. This is especially useful for label-free quantification of biomasses (e.g. lipid droplets) of the particular species of interest - an important task adopted in biofuel applications. Combining machine learning for automated classification, Q-ATOM could be an attractive platform for continuous and real-time ultralarge-scale single-phytoplankton analysis.

  1. Qualitative and quantitative imaging in microgravity combustion

    Science.gov (United States)

    Weiland, Karen J.

    1995-01-01

    An overview of the imaging techniques implemented by researchers in the microgravity combustion program shows that for almost any system, imaging of the flame may be accomplished in a variety of ways. Standard and intensified video, high speed, and infrared cameras and fluorescence, laser schlieren, rainbow schlieren, soot volume fraction, and soot temperature imaging have all been used in the laboratory and many in reduced gravity to make the necessary experimental measurements.

  2. Principle and applications of terahertz molecular imaging.

    Science.gov (United States)

    Son, Joo-Hiuk

    2013-05-31

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

  3. Advanced imaging of colorectal cancer: From anatomy to molecular imaging

    OpenAIRE

    García-Figueiras, Roberto; Baleato-González, Sandra; Padhani, Anwar R.; Marhuenda, Ana; Luna, Antonio; Alcalá, Lidia; Carballo-Castro, Ana; Álvarez-Castro, Ana

    2016-01-01

    Abstract Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent...

  4. Quantitative methods for the analysis of electron microscope images

    DEFF Research Database (Denmark)

    Skands, Peter Ulrik Vallø

    1996-01-01

    The topic of this thesis is an general introduction to quantitative methods for the analysis of digital microscope images. The images presented are primarily been acquired from Scanning Electron Microscopes (SEM) and interfermeter microscopes (IFM). The topic is approached though several examples...... foundation of the thesis fall in the areas of: 1) Mathematical Morphology; 2) Distance transforms and applications; and 3) Fractal geometry. Image analysis opens in general the possibility of a quantitative and statistical well founded measurement of digital microscope images. Herein lies also the conditions...

  5. Quantitative real-time imaging of glutathione

    Science.gov (United States)

    Glutathione plays many important roles in biological processes; however, the dynamic changes of glutathione concentrations in living cells remain largely unknown. Here, we report a reversible reaction-based fluorescent probe—designated as RealThiol (RT)—that can quantitatively monitor the real-time ...

  6. Chromatic Image Analysis For Quantitative Thermal Mapping

    Science.gov (United States)

    Buck, Gregory M.

    1995-01-01

    Chromatic image analysis system (CIAS) developed for use in noncontact measurements of temperatures on aerothermodynamic models in hypersonic wind tunnels. Based on concept of temperature coupled to shift in color spectrum for optical measurement. Video camera images fluorescence emitted by phosphor-coated model at two wavelengths. Temperature map of model then computed from relative brightnesses in video images of model at those wavelengths. Eliminates need for intrusive, time-consuming, contact temperature measurements by gauges, making it possible to map temperatures on complex surfaces in timely manner and at reduced cost.

  7. Molecular Histopathology by Spectrally Reconstructed Nonlinear Interferometric Vibrational Imaging

    Science.gov (United States)

    Chowdary, Praveen D.; Jiang, Zhi; Chaney, Eric J.; Benalcazar, Wladimir A.; Marks, Daniel L.; Gruebele, Martin; Boppart, Stephen A.

    2011-01-01

    Sensitive assays for rapid quantitative analysis of histologic sections, resected tissue specimens, or in situ tissue are highly desired for early disease diagnosis. Stained histopathology is the gold standard but remains a subjective practice on processed tissue taking from hours to days. We describe a microscopy technique that obtains a sensitive and accurate color-coded image from intrinsic molecular markers. Spectrally reconstructed nonlinear interferometric vibrational imaging can differentiate cancer versus normal tissue sections with greater than 99% confidence interval in a preclinical rat breast cancer model and define cancer boundaries to ±100 μm with greater than 99% confidence interval, using fresh unstained tissue sections imaged in less than 5 minutes. By optimizing optical sources and beam delivery, this technique can potentially enable real-time point-of-care optical molecular imaging and diagnosis. PMID:21098699

  8. Ultrasound Molecular Imaging: Moving Towards Clinical Translation

    Science.gov (United States)

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

    2015-01-01

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

  9. Ultrasound molecular imaging: Moving toward clinical translation.

    Science.gov (United States)

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

    2015-09-01

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

  10. Acoustic and Photoacoustic Molecular Imaging of Cancer

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24187042

  11. Acoustic and photoacoustic molecular imaging of cancer.

    Science.gov (United States)

    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.

  12. Molecular imaging of movement disorders

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    -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 parietooccipital 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.

  13. Quantitative Morphological and Biochemical Studies on Human Downy Hairs using 3-D Quantitative Phase Imaging

    CERN Document Server

    Lee, SangYun; Lee, Yuhyun; Park, Sungjin; Shin, Heejae; Yang, Jongwon; Ko, Kwanhong; Park, HyunJoo; Park, YongKeun

    2015-01-01

    This study presents the morphological and biochemical findings on human downy arm hairs using 3-D quantitative phase imaging techniques. 3-D refractive index tomograms and high-resolution 2-D synthetic aperture images of individual downy arm hairs were measured using a Mach-Zehnder laser interferometric microscopy equipped with a two-axis galvanometer mirror. From the measured quantitative images, the biochemical and morphological parameters of downy hairs were non-invasively quantified including the mean refractive index, volume, cylinder, and effective radius of individual hairs. In addition, the effects of hydrogen peroxide on individual downy hairs were investigated.

  14. Partial Volume Correction in Quantitative Amyloid Imaging

    Science.gov (United States)

    Su, Yi; Blazey, Tyler M.; Snyder, Abraham Z.; Raichle, Marcus E.; Marcus, Daniel S.; Ances, Beau M.; Bateman, Randall J.; Cairns, Nigel J.; Aldea, Patricia; Cash, Lisa; Christensen, Jon J.; Friedrichsen, Karl; Hornbeck, Russ C.; Farrar, Angela M.; Owen, Christopher J.; Mayeux, Richard; Brickman, Adam M.; Klunk, William; Price, Julie C.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew J.; Sperling, Reisa A.; Johnson, Keith A.; Schofield, Peter R.; Buckles, Virginia; Morris, John C.; Benzinger, Tammie. LS.

    2014-01-01

    Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition. PMID:25485714

  15. Quantitative spectrally resolved imaging through a spectrograph

    NARCIS (Netherlands)

    Tolboom, RAL; Sijtsema, NM; ter Meulen, JJ; Dam, N.J.

    2003-01-01

    A grating spectrograph can be used for spectrally selective two-dimensional imaging if it is operated with a broad entrance slit. The resulting intensity distribution in its exit plane is a one-dimensional convolution of the spatial and spectral distributions of incident light. We present a dedicate

  16. Oncological image analysis: medical and molecular image analysis

    Science.gov (United States)

    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.

  17. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

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

  18. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

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

  19. Issues in Quantitative Analysis of Ultraviolet Imager (UV) Data: Airglow

    Science.gov (United States)

    Germany, G. A.; Richards, P. G.; Spann, J. F.; Brittnacher, M. J.; Parks, G. K.

    1999-01-01

    The GGS Ultraviolet Imager (UVI) has proven to be especially valuable in correlative substorm, auroral morphology, and extended statistical studies of the auroral regions. Such studies are based on knowledge of the location, spatial, and temporal behavior of auroral emissions. More quantitative studies, based on absolute radiometric intensities from UVI images, require a more intimate knowledge of the instrument behavior and data processing requirements and are inherently more difficult than studies based on relative knowledge of the oval location. In this study, UVI airglow observations are analyzed and compared with model predictions to illustrate issues that arise in quantitative analysis of UVI images. These issues include instrument calibration, long term changes in sensitivity, and imager flat field response as well as proper background correction. Airglow emissions are chosen for this study because of their relatively straightforward modeling requirements and because of their implications for thermospheric compositional studies. The analysis issues discussed here, however, are identical to those faced in quantitative auroral studies.

  20. Issues in Quantitative Analysis of Ultraviolet Imager (UV) Data: Airglow

    Science.gov (United States)

    Germany, G. A.; Richards, P. G.; Spann, J. F.; Brittnacher, M. J.; Parks, G. K.

    1999-01-01

    The GGS Ultraviolet Imager (UVI) has proven to be especially valuable in correlative substorm, auroral morphology, and extended statistical studies of the auroral regions. Such studies are based on knowledge of the location, spatial, and temporal behavior of auroral emissions. More quantitative studies, based on absolute radiometric intensities from UVI images, require a more intimate knowledge of the instrument behavior and data processing requirements and are inherently more difficult than studies based on relative knowledge of the oval location. In this study, UVI airglow observations are analyzed and compared with model predictions to illustrate issues that arise in quantitative analysis of UVI images. These issues include instrument calibration, long term changes in sensitivity, and imager flat field response as well as proper background correction. Airglow emissions are chosen for this study because of their relatively straightforward modeling requirements and because of their implications for thermospheric compositional studies. The analysis issues discussed here, however, are identical to those faced in quantitative auroral studies.

  1. Molecular imaging of the tumor microenvironment.

    Science.gov (United States)

    Zhou, Zhuxian; Lu, Zheng-Rong

    2017-04-01

    The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and resistance to therapy. It is different from normal tissue in the extracellular matrix, vascular and lymphatic networks, as well as physiologic conditions. Molecular imaging of the tumor microenvironment provides a better understanding of its function in cancer biology, and thus allowing for the design of new diagnostics and therapeutics for early cancer diagnosis and treatment. The clinical translation of cancer molecular imaging is often hampered by the high cost of commercialization of targeted imaging agents as well as the limited clinical applications and small market size of some of the agents. Because many different cancer types share similar tumor microenvironment features, the ability to target these biomarkers has the potential to provide clinically translatable molecular imaging technologies for a spectrum of cancers and broad clinical applications. There has been significant progress in targeting the tumor microenvironment for cancer molecular imaging. In this review, we summarize the principles and strategies of recent advances made in molecular imaging of the tumor microenvironment, using various imaging modalities for early detection and diagnosis of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Some selected quantitative methods of thermal image analysis in Matlab.

    Science.gov (United States)

    Koprowski, Robert

    2016-05-01

    The paper presents a new algorithm based on some selected automatic quantitative methods for analysing thermal images. It shows the practical implementation of these image analysis methods in Matlab. It enables to perform fully automated and reproducible measurements of selected parameters in thermal images. The paper also shows two examples of the use of the proposed image analysis methods for the area of ​​the skin of a human foot and face. The full source code of the developed application is also provided as an attachment. The main window of the program during dynamic analysis of the foot thermal image.

  3. Imaging Performance of Quantitative Transmission Ultrasound

    Directory of Open Access Journals (Sweden)

    Mark W. Lenox

    2015-01-01

    Full Text Available Quantitative Transmission Ultrasound (QTUS is a tomographic transmission ultrasound modality that is capable of generating 3D speed-of-sound maps of objects in the field of view. It performs this measurement by propagating a plane wave through the medium from a transmitter on one side of a water tank to a high resolution receiver on the opposite side. This information is then used via inverse scattering to compute a speed map. In addition, the presence of reflection transducers allows the creation of a high resolution, spatially compounded reflection map that is natively coregistered to the speed map. A prototype QTUS system was evaluated for measurement and geometric accuracy as well as for the ability to correctly determine speed of sound.

  4. Microbubbles for Molecular Imaging and Drug Delivery

    NARCIS (Netherlands)

    I. Skachkov (Ilya)

    2016-01-01

    markdownabstractIn my thesis, microbubbles (MBs) for ultrasound (US) imaging, ultrasound molecular imaging, and drug delivery were studied. Microbubbles are gas-encapsulated lipid or polymer shell coated micro-particles, widely used as ultrasound contrast agents (UCA). MBs oscillate in response to t

  5. Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers.

    Science.gov (United States)

    Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David

    2013-08-01

    A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data.

  6. Molecular imaging with dynamic contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-15

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

  7. Informatics methods to enable sharing of quantitative imaging research data.

    Science.gov (United States)

    Levy, Mia A; Freymann, John B; Kirby, Justin S; Fedorov, Andriy; Fennessy, Fiona M; Eschrich, Steven A; Berglund, Anders E; Fenstermacher, David A; Tan, Yongqiang; Guo, Xiaotao; Casavant, Thomas L; Brown, Bartley J; Braun, Terry A; Dekker, Andre; Roelofs, Erik; Mountz, James M; Boada, Fernando; Laymon, Charles; Oborski, Matt; Rubin, Daniel L

    2012-11-01

    The National Cancer Institute Quantitative Research Network (QIN) is a collaborative research network whose goal is to share data, algorithms and research tools to accelerate quantitative imaging research. A challenge is the variability in tools and analysis platforms used in quantitative imaging. Our goal was to understand the extent of this variation and to develop an approach to enable sharing data and to promote reuse of quantitative imaging data in the community. We performed a survey of the current tools in use by the QIN member sites for representation and storage of their QIN research data including images, image meta-data and clinical data. We identified existing systems and standards for data sharing and their gaps for the QIN use case. We then proposed a system architecture to enable data sharing and collaborative experimentation within the QIN. There are a variety of tools currently used by each QIN institution. We developed a general information system architecture to support the QIN goals. We also describe the remaining architecture gaps we are developing to enable members to share research images and image meta-data across the network. As a research network, the QIN will stimulate quantitative imaging research by pooling data, algorithms and research tools. However, there are gaps in current functional requirements that will need to be met by future informatics development. Special attention must be given to the technical requirements needed to translate these methods into the clinical research workflow to enable validation and qualification of these novel imaging biomarkers. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Quantitative performance assessments for neuromagnetic imaging systems.

    Science.gov (United States)

    Koga, Ryo; Hiyama, Ei; Matsumoto, Takuya; Sekihara, Kensuke

    2013-01-01

    We have developed a Monte-Carlo simulation method to assess the performance of neuromagnetic imaging systems using two kinds of performance metrics: A-prime metric and spatial resolution. We compute these performance metrics for virtual sensor systems having 80, 160, 320, and 640 sensors, and discuss how the system performance is improved, depending on the number of sensors. We also compute these metrics for existing whole-head MEG systems, MEGvision™ (Yokogawa Electric Corporation, Tokyo, Japan) that uses axial-gradiometer sensors, and TRIUX™ (Elekta Corporate, Stockholm, Sweden) that uses planar-gradiometer and magnetometer sensors. We discuss performance comparisons between these significantly different systems.

  9. Molecular Imaging of Autoimmune Diseases and Inflammation

    Directory of Open Access Journals (Sweden)

    S. Anna Sargsyan

    2012-05-01

    Full Text Available Molecular imaging methods allow the noninvasive detection and localization of specific molecules. Agents that report on molecular disease biomarkers can be used to diagnose and monitor disease. Many inflammatory diseases have molecular signatures within altered tissues. Although tissue biopsy is still the gold standard for detecting these signatures, several molecular imaging markers have been developed. Pharmacologic agents that block specific immune molecules have recently entered the clinic, and these drugs have already transformed the way we care for patients with immune-mediated diseases. The use of immunomodulatory drugs is usually guided by clinical assessment of the patient's response. Unfortunately, clinical assessment may miss the signs of inflammation, and many of the serologic markers of immune-mediated diseases correlate poorly with the underlying inflammatory activity within target tissues. Molecular imaging methods have the potential to improve our ability to detect and characterize tissue inflammation. We discuss some of the molecular signatures of immune activation and review molecular imaging methods that have been developed to detect active tissue inflammation.

  10. Quantitative and qualitative analysis and interpretation of CT perfusion imaging.

    Science.gov (United States)

    Valdiviezo, Carolina; Ambrose, Marietta; Mehra, Vishal; Lardo, Albert C; Lima, Joao A C; George, Richard T

    2010-12-01

    Coronary artery disease (CAD) remains the leading cause of death in the United States. Rest and stress myocardial perfusion imaging has an important role in the non-invasive risk stratification of patients with CAD. However, diagnostic accuracies have been limited, which has led to the development of several myocardial perfusion imaging techniques. Among them, myocardial computed tomography perfusion imaging (CTP) is especially interesting as it has the unique capability of providing anatomic- as well as coronary stenosis-related functional data when combined with computed tomography angiography (CTA). The primary aim of this article is to review the qualitative, semi-quantitative, and quantitative analysis approaches to CTP imaging. In doing so, we will describe the image data required for each analysis and discuss the advantages and disadvantages of each approach.

  11. Molecular Imaging of Urogenital Diseases

    Science.gov (United States)

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

    2013-01-01

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

  12. Quantitative multimodality imaging in cancer research and therapy.

    Science.gov (United States)

    Yankeelov, Thomas E; Abramson, Richard G; Quarles, C Chad

    2014-11-01

    Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein.

  13. Quantitative image quality evaluation for cardiac CT reconstructions

    Science.gov (United States)

    Tseng, Hsin-Wu; Fan, Jiahua; Kupinski, Matthew A.; Balhorn, William; Okerlund, Darin R.

    2016-03-01

    Maintaining image quality in the presence of motion is always desirable and challenging in clinical Cardiac CT imaging. Different image-reconstruction algorithms are available on current commercial CT systems that attempt to achieve this goal. It is widely accepted that image-quality assessment should be task-based and involve specific tasks, observers, and associated figures of merits. In this work, we developed an observer model that performed the task of estimating the percentage of plaque in a vessel from CT images. We compared task performance of Cardiac CT image data reconstructed using a conventional FBP reconstruction algorithm and the SnapShot Freeze (SSF) algorithm, each at default and optimal reconstruction cardiac phases. The purpose of this work is to design an approach for quantitative image-quality evaluation of temporal resolution for Cardiac CT systems. To simulate heart motion, a moving coronary type phantom synchronized with an ECG signal was used. Three different percentage plaques embedded in a 3 mm vessel phantom were imaged multiple times under motion free, 60 bpm, and 80 bpm heart rates. Static (motion free) images of this phantom were taken as reference images for image template generation. Independent ROIs from the 60 bpm and 80 bpm images were generated by vessel tracking. The observer performed estimation tasks using these ROIs. Ensemble mean square error (EMSE) was used as the figure of merit. Results suggest that the quality of SSF images is superior to the quality of FBP images in higher heart-rate scans.

  14. Molecular and Functional Imaging of Internet Addiction

    Directory of Open Access Journals (Sweden)

    Yunqi Zhu

    2015-01-01

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

  15. Molecular and functional imaging of internet addiction.

    Science.gov (United States)

    Zhu, Yunqi; Zhang, Hong; Tian, Mei

    2015-01-01

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

  16. Accuracy of Image Analysis in Quantitative Study of Cement Paste

    Directory of Open Access Journals (Sweden)

    Feng Shu-Xia

    2016-01-01

    Full Text Available Quantitative study on cement paste especially blended cement paste has been a hot and difficult issue over the years, and the technique of backscattered electron image analysis showed unique advantages in this field. This paper compared the test results of cement hydration degree, Ca(OH2 content and pore size distribution in pure pastes by image analysis and other methods. Then the accuracy of qualitative study by image analysis was analyzed. The results showed that image analysis technique had displayed higher accuracy in quantifying cement hydration degree and Ca(OH2 content than non-evaporable water test and thermal analysis respectively.

  17. Quantitative Pulmonary Imaging Using Computed Tomography and Magnetic Resonance Imaging

    Science.gov (United States)

    Washko, George R.; Parraga, Grace; Coxson, Harvey O.

    2011-01-01

    Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic, and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review we will focus on two of them, x-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge. PMID:22142490

  18. Molecular imaging of Alzheimer disease pathology.

    Science.gov (United States)

    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. © 2014 by American Journal of Neuroradiology.

  19. Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

    Science.gov (United States)

    Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

    2016-12-01

    Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

  20. Prior image constrained compressed sensing: a quantitative performance evaluation

    Science.gov (United States)

    Thériault Lauzier, Pascal; Tang, Jie; Chen, Guang-Hong

    2012-03-01

    The appeal of compressed sensing (CS) in the context of medical imaging is undeniable. In MRI, it could enable shorter acquisition times while in CT, it has the potential to reduce the ionizing radiation dose imparted to patients. However, images reconstructed using a CS-based approach often show an unusual texture and a potential loss in spatial resolution. The prior image constrained compressed sensing (PICCS) algorithm has been shown to enable accurate image reconstruction at lower levels of sampling. This study systematically evaluates an implementation of PICCS applied to myocardial perfusion imaging with respect to two parameters of its objective function. The prior image parameter α was shown here to yield an optimal image quality in the range 0.4 to 0.5. A quantitative evaluation in terms of temporal resolution, spatial resolution, noise level, noise texture, and reconstruction accuracy was performed.

  1. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

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

  2. Quantitative amyloid imaging using image-derived arterial input function.

    Directory of Open Access Journals (Sweden)

    Yi Su

    Full Text Available Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer's disease (AD. Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB PET imaging and MR imaging including a time-of-flight (TOF MR angiography (MRA scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (VT was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVRkinetic without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVRREF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80. The estimated cerebellum VT was in line with literature reported values and the variability of cerebellum VT in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference

  3. Quantitative amyloid imaging using image-derived arterial input function.

    Science.gov (United States)

    Su, Yi; Blazey, Tyler M; Snyder, Abraham Z; Raichle, Marcus E; Hornbeck, Russ C; Aldea, Patricia; Morris, John C; Benzinger, Tammie L S

    2015-01-01

    Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer's disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (VT) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVRkinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVRREF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum VT was in line with literature reported values and the variability of cerebellum VT in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may

  4. Molecular imaging of atherosclerosis in translational medicine

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-05-15

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

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

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2015-09-01

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

  6. Generalized PSF modeling for optimized quantitation in PET imaging

    Science.gov (United States)

    Ashrafinia, Saeed; Mohy-ud-Din, Hassan; Karakatsanis, Nicolas A.; Jha, Abhinav K.; Casey, Michael E.; Kadrmas, Dan J.; Rahmim, Arman

    2017-06-01

    Point-spread function (PSF) modeling offers the ability to account for resolution degrading phenomena within the PET image generation framework. PSF modeling improves resolution and enhances contrast, but at the same time significantly alters image noise properties and induces edge overshoot effect. Thus, studying the effect of PSF modeling on quantitation task performance can be very important. Frameworks explored in the past involved a dichotomy of PSF versus no-PSF modeling. By contrast, the present work focuses on quantitative performance evaluation of standard uptake value (SUV) PET images, while incorporating a wide spectrum of PSF models, including those that under- and over-estimate the true PSF, for the potential of enhanced quantitation of SUVs. The developed framework first analytically models the true PSF, considering a range of resolution degradation phenomena (including photon non-collinearity, inter-crystal penetration and scattering) as present in data acquisitions with modern commercial PET systems. In the context of oncologic liver FDG PET imaging, we generated 200 noisy datasets per image-set (with clinically realistic noise levels) using an XCAT anthropomorphic phantom with liver tumours of varying sizes. These were subsequently reconstructed using the OS-EM algorithm with varying PSF modelled kernels. We focused on quantitation of both SUVmean and SUVmax, including assessment of contrast recovery coefficients, as well as noise-bias characteristics (including both image roughness and coefficient of-variability), for different tumours/iterations/PSF kernels. It was observed that overestimated PSF yielded more accurate contrast recovery for a range of tumours, and typically improved quantitative performance. For a clinically reasonable number of iterations, edge enhancement due to PSF modeling (especially due to over-estimated PSF) was in fact seen to lower SUVmean bias in small tumours. Overall, the results indicate that exactly matched PSF

  7. Quantitative Comparison of Y-90 and Ge-68 PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sangkeun; Kwak, Shin Hye; Lee, Jeong A; Song, Han Kyeol; Kang, Joo Hyun; Lim, Sang Moo; KIm, Kyeong Min [Korea Institute of Raiological and Medical Sciences, Seoul (Korea, Republic of); Jeong, Su Young [Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of)

    2014-05-15

    The purpose of this study was to assess statistical characteristics and to improve count rate of image for enhancing Y-90 image quality by using non-parametric bootstrap method. The results showed that Y-90 PET image can be improved using non-parametric bootstrap method. PET data was able to be improved using non-parametric bootstrap method and it was verified with showing improved prompts rate. Y-90 PET image quality was improved and bias indicated that the bootstrapped image was more similar to the gold standard than other images. The non-parametric bootstrap method will be useful tool for enhancing Y-90 PET image and it will be expected to reduce time for acquisition and to elevate performance for diagnosis and treatment. Yttrium-90 (Y-90) radioembolization is one of the treatment methods unrespectable stage of hepatocellular carcinoma (HCC) and metastatic colon cancer to the liver. However, Y-90 radioembolization is a catheter-based therapy that delivers internal radiation to tumors, it results in greater radiation exposure to the tumors than using external radiation. Also, unlike other current therapies for the treatment of unresectable liver tumors, Y-90 radioembolization is much less often associated with toxicities such as abdominal pain, fever, nausea, and vomiting. Therefore Y-90 has been received much interest and studied by many researchers. Imaging of Y-90 has been conducted using most commonly gamma camera but quantitative PET imaging is required due to low sensitivity and resolution. Y-90 imaging is generally performed with SPECT by Bremsstrahlung photons. Unfortunately, the low image quality due to the nature of the Bremsstrahlung photon limits the quantitative accuracy of Y-90 SPECT. To overcome this limitation in SPECT imaging, Y-90 PET has been suggested as an alternative.

  8. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

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

  9. Quantitatively accurate calculations of conductance and thermopower of molecular junctions

    DEFF Research Database (Denmark)

    Markussen, Troels; Jin, Chengjun; Thygesen, Kristian Sommer

    2013-01-01

    ) connected to gold electrodes using first‐principles calculations. We find excellent agreement with experiments for both molecules when exchange–correlation effects are described by the many‐body GW approximation. In contrast, results from standard density functional theory (DFT) deviate from experiments......‐interaction errors and image charge effects. Finally, we show that the conductance and thermopower of the considered junctions are relatively insensitive to the metal–molecule bonding geometry. Our results demonstrate that electronic and thermoelectric properties of molecular junctions can be predicted from first‐principles...... calculations when exchange–correlation effects are taken properly into account....

  10. Ultrasound introscopic image quantitative characteristics for medical diagnosis

    Science.gov (United States)

    Novoselets, Mikhail K.; Sarkisov, Sergey S.; Gridko, Alexander N.; Tcheban, Anatoliy K.

    1993-09-01

    The results on computer aided extraction of quantitative characteristics (QC) of ultrasound introscopic images for medical diagnosis are presented. Thyroid gland (TG) images of Chernobil Accident sufferers are considered. It is shown that TG diseases can be associated with some values of selected QCs of random echo distribution in the image. The possibility of these QCs usage for TG diseases recognition in accordance with calculated values is analyzed. The role of speckle noise elimination in the solution of the problem on TG diagnosis is considered too.

  11. Semiconductor defect metrology using laser-based quantitative phase imaging

    Science.gov (United States)

    Zhou, Renjie; Edwards, Chris; Popescu, Gabriel; Goddard, Lynford

    2015-03-01

    A highly sensitive laser-based quantitative phase imaging tool, using an epi-illumination diffraction phase microscope, has been developed for silicon wafer defect inspection. The first system used a 532 nm solid-state laser and detected 20 nm by 100 nm by 110 nm defects in a 22 nm node patterned silicon wafer. The second system, using a 405 nm diode laser, is more sensitive and has enabled detection of 15 nm by 90 nm by 35 nm defects in a 9 nm node densely patterned silicon wafer. In addition to imaging, wafer scanning and image-post processing are also crucial for defect detection.

  12. A Targeting Microbubble for Ultrasound Molecular Imaging.

    Directory of Open Access Journals (Sweden)

    James Shue-Min Yeh

    Full Text Available Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (streptavidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(streptavidin 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.To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.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.Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i-(iii desired for

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

  14. CMOS APS detector characterization for quantitative X-ray imaging

    Energy Technology Data Exchange (ETDEWEB)

    Endrizzi, Marco, E-mail: m.endrizzi@ucl.ac.uk [Dipartimento di Fisica, Università di Siena, Via Roma 56, 53100 Siena (Italy); Istituto Nazionale di Fisica Nucleare INFN, sezione di Pisa, 56127 Pisa (Italy); Oliva, Piernicola [Dipartimento di Chimica e Farmacia, Università di Sassari, via Piandanna 4, 07100 Sassari (Italy); Istituto Nazionale di Fisica Nucleare INFN, Sezione di Cagliari, 09042 Cagliari (Italy); Golosio, Bruno [Sezione di Matematica, Fisica e Ingegneria dell' Informazione, Università di Sassari, via Piandanna 4, 07100 Sassari (Italy); Istituto Nazionale di Fisica Nucleare INFN, Sezione di Cagliari, 09042 Cagliari (Italy); Delogu, Pasquale [Dipartimento di Fisica “E. Fermi”, Università di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare INFN, sezione di Pisa, 56127 Pisa (Italy)

    2013-03-01

    An X-ray Imaging detector based on CMOS Active Pixel Sensor and structured scintillator is characterized for quantitative X-ray imaging in the energy range 11–30 keV. Linearity, dark noise, spatial resolution and flat-field correction are the characteristics of the detector subject of investigation. The detector response, in terms of mean Analog-to-Digital Unit and noise, is modeled as a function of the energy and intensity of the X-rays. The model is directly tested using monochromatic X-ray beams and it is also indirectly validated by means of polychromatic X-ray-tube spectra. Such a characterization is suitable for quantitative X-ray imaging and the model can be used in simulation studies that take into account the actual performance of the detector.

  15. Radiogenomic imaging-linking diagnostic imaging and molecular diagnostics

    Institute of Scientific and Technical Information of China (English)

    Mathias; Goyen

    2014-01-01

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

  16. NAOMI: nanoparticle assisted optical molecular imaging

    Science.gov (United States)

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

    2006-02-01

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

  17. Towards molecular imaging by means of MRI

    NARCIS (Netherlands)

    Norek, M.

    2008-01-01

    The work presented in the thesis is focused on the design of highly efficient contrast agents for molecular imaging by means of MRI based on the detailed physical characterization of the given material. Specifically, attention is paid on the development of contrast agents for magnetic fields higher

  18. Assessing the Reliability of Quantitative Imaging of Sm-153

    Science.gov (United States)

    Poh, Zijie; Dagan, Maáyan; Veldman, Jeanette; Trees, Brad

    2013-03-01

    Samarium-153 is used for palliation of and recently has been investigated for therapy for bone metastases. Patient specific dosing of Sm-153 is based on quantitative single-photon emission computed tomography (SPECT) and knowing the accuracy and precision of image-based estimates of the in vivo activity distribution. Physical phantom studies are useful for estimating these in simple objects, but do not model realistic activity distributions. We are using realistic Monte Carlo simulations combined with a realistic digital phantom modeling human anatomy to assess the accuracy and precision of Sm-153 SPECT. Preliminary data indicates that we can simulate projection images and reconstruct them with compensation for various physical image degrading factors, such as attenuation and scatter in the body as well as non-idealities in the imaging system, to provide realistic SPECT images.

  19. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    Science.gov (United States)

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively.

  20. Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney Disease.

    Science.gov (United States)

    Gao, Jing; Perlman, Alan; Kalache, Safa; Berman, Nathaniel; Seshan, Surya; Salvatore, Steven; Smith, Lindsey; Wehrli, Natasha; Waldron, Levi; Kodali, Hanish; Chevalier, James

    2017-04-13

    To evaluate the value of multiparametric quantitative ultrasound imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic findings as reference standards. We prospectively measured multiparametric quantitative ultrasound markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD before kidney biopsy and 10 healthy volunteers. Based on all pathologic (glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and edema) scores, the patients with CKD were classified into mild (no grade 3 and quantitative ultrasound parameters included kidney length, cortical thickness, pixel intensity, parenchymal shear wave velocity, intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index. We tested the difference in quantitative ultrasound parameters among mild CKD, moderate to severe CKD, and healthy controls using analysis of variance, analyzed correlations of quantitative ultrasound parameters with pathologic scores and the estimated glomerular filtration rate (GFR) using Pearson correlation coefficients, and examined the diagnostic performance of quantitative ultrasound parameters in determining moderate CKD and an estimated GFR of less than 60 mL/min/1.73 m(2) using receiver operating characteristic curve analysis. There were significant differences in cortical thickness, pixel intensity, PSV, and EDV among the 3 groups (all P quantitative ultrasound parameters, the top areas under the receiver operating characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated GFR of less than 60 mL/min/1.73 m(2) . Moderate to good correlations were found for PSV, EDV, and pixel intensity with pathologic scores and estimated GFR. The PSV, EDV, and pixel intensity are valuable in determining moderate to severe CKD. The value of shear wave velocity in

  1. Quantitative analysis of in vivo confocal microscopy images: a review.

    Science.gov (United States)

    Patel, Dipika V; McGhee, Charles N

    2013-01-01

    In vivo confocal microscopy (IVCM) is a non-invasive method of examining the living human cornea. The recent trend towards quantitative studies using IVCM has led to the development of a variety of methods for quantifying image parameters. When selecting IVCM images for quantitative analysis, it is important to be consistent regarding the location, depth, and quality of images. All images should be de-identified, randomized, and calibrated prior to analysis. Numerous image analysis software are available, each with their own advantages and disadvantages. Criteria for analyzing corneal epithelium, sub-basal nerves, keratocytes, endothelium, and immune/inflammatory cells have been developed, although there is inconsistency among research groups regarding parameter definition. The quantification of stromal nerve parameters, however, remains a challenge. Most studies report lower inter-observer repeatability compared with intra-observer repeatability, and observer experience is known to be an important factor. Standardization of IVCM image analysis through the use of a reading center would be crucial for any future large, multi-centre clinical trials using IVCM.

  2. Summary of Quantitative Interpretation of Image Far Ultraviolet Auroral Data

    Science.gov (United States)

    Frey, H. U.; Immel, T. J.; Mende, S. B.; Gerard, J.-C.; Hubert, B.; Habraken, S.; Span, J.; Gladstone, G. R.; Bisikalo, D. V.; Shematovich, V. I.; hide

    2002-01-01

    Direct imaging of the magnetosphere by instruments on the IMAGE spacecraft is supplemented by simultaneous observations of the global aurora in three far ultraviolet (FUV) wavelength bands. The purpose of the multi-wavelength imaging is to study the global auroral particle and energy input from thc magnetosphere into the atmosphere. This paper describes provides the method for quantitative interpretation of FUV measurements. The Wide-Band Imaging Camera (WIC) provides broad band ultraviolet images of the aurora with maximum spatial and temporal resolution by imaging the nitrogen lines and bands between 140 and 180 nm wavelength. The Spectrographic Imager (SI), a dual wavelength monochromatic instrument, images both Doppler-shifted Lyman alpha emissions produced by precipitating protons, in the SI-12 channel and OI 135.6 nm emissions in the SI-13 channel. From the SI-12 Doppler shifted Lyman alpha images it is possible to obtain the precipitating proton flux provided assumptions are made regarding the mean energy of the protons. Knowledge of the proton (flux and energy) component allows the calculation of the contribution produced by protons in the WIC and SI-13 instruments. Comparison of the corrected WIC and SI-13 signals provides a measure of the electron mean energy, which can then be used to determine the electron energy fluxun-. To accomplish this reliable modeling emission modeling and instrument calibrations are required. In-flight calibration using early-type stars was used to validate the pre-flight laboratory calibrations and determine long-term trends in sensitivity. In general, very reasonable agreement is found between in-situ measurements and remote quantitative determinations.

  3. Imaging molecular structure with photoelectron diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Boll, Rebecca

    2014-07-02

    The possibility to study the structure of polyatomic gas-phase molecules by photoelectron diffraction is investigated with the goal of developing a method capable of imaging ultrafast photochemical reactions with femtosecond temporal and sub-Angstroem spatial resolution. The fluorine 1s-level of adiabatically laser-aligned 1-ethynyl-4-fluorobenzene (C{sub 8}H{sub 5}F) molecules was ionized by X-ray pulses from the Linac Coherent Light Source Free-Electron Laser, and the angular distributions of photoelectrons with kinetic energies between 30 and 60 eV were recorded by velocity map imaging. Comparison with density functional theory calculations allows relating the measured distributions to the molecular structure. The results of an IR-pump, X-ray-probe experiment on aligned 1,4-dibromobenzene (C{sub 6}H{sub 4}Br{sub 2})molecules are presented to explore the potential of photoelectron diffraction for time-resolved imaging. The influence of the alignment laser pulse on the pumping and probing step is discussed. Laser-alignment is contrasted with determination of the molecular orientation by photoelectron-photoion coincidences for an exemplary data set on 1-ethynyl-4-fluorobenzene molecules recorded at the PETRA III synchrotron. Both methods are evaluated with respect to their applicability to record time-dependent snapshots of molecular structure. The results obtained in this work indicate possible future avenues for investigating ultrafast molecular dynamics using X-ray Free-Electron Lasers.

  4. Imaging molecular geometry with electron momentum spectroscopy

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Zhi-Yi Chen

    2014-01-01

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

  6. Quantitative phase imaging with scanning holographic microscopy: an experimental assesment

    Directory of Open Access Journals (Sweden)

    Tada Yoshitaka

    2006-11-01

    Full Text Available Abstract This paper demonstrates experimentally how quantitative phase information can be obtained in scanning holographic microscopy. Scanning holography can operate in both coherent and incoherent modes, simultaneously if desired, with different detector geometries. A spatially integrating detector provides an incoherent hologram of the object's intensity distribution (absorption and/or fluorescence, for example, while a point detector in a conjugate plane of the pupil provides a coherent hologram of the object's complex amplitude, from which a quantitative measure of its phase distribution can be extracted. The possibility of capturing simultaneously holograms of three-dimensional specimens, leading to three-dimensional reconstructions with absorption contrast, reflectance contrast, fluorescence contrast, as was previously demonstrated, and quantitative phase contrast, as shown here for the first time, opens up new avenues for multimodal imaging in biological studies.

  7. The Quantitative Science of Evaluating Imaging Evidence.

    Science.gov (United States)

    Genders, Tessa S S; Ferket, Bart S; Hunink, M G Myriam

    2017-03-01

    Cardiovascular diagnostic imaging tests are increasingly used in everyday clinical practice, but are often imperfect, just like any other diagnostic test. The performance of a cardiovascular diagnostic imaging test is usually expressed in terms of sensitivity and specificity compared with the reference standard (gold standard) for diagnosing the disease. However, evidence-based application of a diagnostic test also requires knowledge about the pre-test probability of disease, the benefit of making a correct diagnosis, the harm caused by false-positive imaging test results, and potential adverse effects of performing the test itself. To assist in clinical decision making regarding appropriate use of cardiovascular diagnostic imaging tests, we reviewed quantitative concepts related to diagnostic performance (e.g., sensitivity, specificity, predictive values, likelihood ratios), as well as possible biases and solutions in diagnostic performance studies, Bayesian principles, and the threshold approach to decision making. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Ultrasound contrast agents for ultrasound molecular imaging.

    Science.gov (United States)

    Tranquart, F; Arditi, M; Bettinger, T; Frinking, P; Hyvelin, J M; Nunn, A; Pochon, S; Tardy, I

    2014-11-01

    Ultrasound is a real-time imaging technique which is widely used in many clinical applications for its capacity to provide anatomic information with high spatial and temporal resolution. The advent of ultrasound contrast agents in combination with contrast-specific imaging modes has given access to perfusion assessments at an organ level, leading to an improved diagnostic accuracy. More recently, the development of biologically-targeted ultrasound contrast agents has expanded the role of ultrasound even further into molecular imaging applications. Ultrasound molecular imaging can be used to visualize the expression of intravascular markers, and to assess their local presence over time and/or during therapeutic treatment. Major applications are in the field of inflammation and neoangiogenesis due to the strictly intravascular presence of microbubbles. Various technologies have been investigated for attaching the targeting moiety to the shell from simple biotin-avidin constructs to more elaborated insertion within the shell through attachment to PEG residues. This important improvement has allowed a clinical translation of initial pre-clinical investigations, opening the way for an early detection and an accurate characterization of lesions in patients. The combination of anatomic, functional and molecular information/data provided by contrast ultrasound is a powerful tool which is still in its infancy due to the lack of agents suitable for clinical use. The advantages of ultrasound techniques combined with the molecular signature of lesions will represent a significant advance in imaging in the field of personalized medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  9. 3D quantitative phase imaging of neural networks using WDT

    Science.gov (United States)

    Kim, Taewoo; Liu, S. C.; Iyer, Raj; Gillette, Martha U.; Popescu, Gabriel

    2015-03-01

    White-light diffraction tomography (WDT) is a recently developed 3D imaging technique based on a quantitative phase imaging system called spatial light interference microscopy (SLIM). The technique has achieved a sub-micron resolution in all three directions with high sensitivity granted by the low-coherence of a white-light source. Demonstrations of the technique on single cell imaging have been presented previously; however, imaging on any larger sample, including a cluster of cells, has not been demonstrated using the technique. Neurons in an animal body form a highly complex and spatially organized 3D structure, which can be characterized by neuronal networks or circuits. Currently, the most common method of studying the 3D structure of neuron networks is by using a confocal fluorescence microscope, which requires fluorescence tagging with either transient membrane dyes or after fixation of the cells. Therefore, studies on neurons are often limited to samples that are chemically treated and/or dead. WDT presents a solution for imaging live neuron networks with a high spatial and temporal resolution, because it is a 3D imaging method that is label-free and non-invasive. Using this method, a mouse or rat hippocampal neuron culture and a mouse dorsal root ganglion (DRG) neuron culture have been imaged in order to see the extension of processes between the cells in 3D. Furthermore, the tomogram is compared with a confocal fluorescence image in order to investigate the 3D structure at synapses.

  10. Novel method for ANA quantitation using IIF imaging system.

    Science.gov (United States)

    Peng, Xiaodong; Tang, Jiangtao; Wu, Yongkang; Yang, Bin; Hu, Jing

    2014-02-01

    A variety of antinuclear antibodies (ANAs) are found in the serum of patients with autoimmune diseases. The detection of abnormal ANA titers is a critical criterion for diagnosis of systemic lupus erythematosus (SLE) and other connective tissue diseases. Indirect immunofluorescence assay (IIF) on HEp-2 cells is the gold standard method to determine the presence of ANA and therefore provides information about the localization of autoantigens that are useful for diagnosis. However, its utility was limited in prognosing and monitoring of disease activity due to the lack of standardization in performing the technique, subjectivity in interpreting the results and the fact that it is only semi-quantitative. On the other hand, ELISA for the detection of ANA can quantitate ANA but could not provide further information about the localization of the autoantigens. It would be ideal to integrate both of the quantitative and qualitative methods. To address this issue, this study was conducted to quantitatively detect ANAs by using IIF imaging analysis system. Serum samples from patients with ANA positive (including speckled, homogeneous, nuclear mixture and cytoplasmic mixture patterns) and negative were detected for ANA titers by the classical IIF and analyzed by an image system, the image of each sample was acquired by the digital imaging system and the green fluorescence intensity was quantified by the Image-Pro plus software. A good correlation was found in between two methods and the correlation coefficients (R(2)) of various ANA patterns were 0.942 (speckled), 0.942 (homogeneous), 0.923 (nuclear mixture) and 0.760 (cytoplasmic mixture), respectively. The fluorescence density was linearly correlated with the log of ANA titers in various ANA patterns (R(2)>0.95). Moreover, the novel ANA quantitation method showed good reproducibility (F=0.091, p>0.05) with mean±SD and CV% of positive, and negative quality controls were equal to 126.4±9.6 and 7.6%, 10.4±1.25 and 12

  11. Quantitative imaging of complex samples by spiral phase contrast microscopy.

    Science.gov (United States)

    Bernet, Stefan; Jesacher, Alexander; Fürhapter, Severin; Maurer, Christian; Ritsch-Marte, Monika

    2006-05-01

    Recently a spatial spiral phase filter in a Fourier plane of a microscopic imaging setup has been demonstrated to produce edge enhancement and relief-like shadow formation of amplitude and phase samples. Here we demonstrate that a sequence of at least 3 spatially filtered images, which are recorded with different rotational orientations of the spiral phase plate, can be used to obtain a quantitative reconstruction of both, amplitude and phase information of a complex microscopic sample, i.e. an object consisting of mixed absorptive and refractive components. The method is demonstrated using a calibrated phase sample, and an epithelial cheek cell.

  12. Quantitative colorimetric-imaging analysis of nickel in iron meteorites.

    Science.gov (United States)

    Zamora, L Lahuerta; López, P Alemán; Fos, G M Antón; Algarra, R Martín; Romero, A M Mellado; Calatayud, J Martínez

    2011-02-15

    A quantitative analytical imaging approach for determining the nickel content of metallic meteorites is proposed. The approach uses a digital image of a series of standard solutions of the nickel-dimethylglyoxime coloured chelate and a meteorite sample solution subjected to the same treatment as the nickel standards for quantitation. The image is processed with suitable software to assign a colour-dependent numerical value (analytical signal) to each standard. Such a value is directly proportional to the analyte concentration, which facilitates construction of a calibration graph where the value for the unknown sample can be interpolated to calculate the nickel content of the meteorite. The results thus obtained were validated by comparison with the official, ISO-endorsed spectrophotometric method for nickel. The proposed method is fairly simple and inexpensive; in fact, it uses a commercially available digital camera as measuring instrument and the images it provides are processed with highly user-friendly public domain software (specifically, ImageJ, developed by the National Institutes of Health and freely available for download on the Internet). In a scenario dominated by increasingly sophisticated and expensive equipment, the proposed method provides a cost-effective alternative based on simple, robust hardware that is affordable and can be readily accessed worldwide. This can be especially advantageous for countries were available resources for analytical equipment investments are scant. The proposed method is essentially an adaptation of classical chemical analysis to current, straightforward, robust, cost-effective instrumentation. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Quantitative nanoscale vortex imaging using a cryogenic quantum magnetometer.

    Science.gov (United States)

    Thiel, L; Rohner, D; Ganzhorn, M; Appel, P; Neu, E; Müller, B; Kleiner, R; Koelle, D; Maletinsky, P

    2016-08-01

    Microscopic studies of superconductors and their vortices play a pivotal role in understanding the mechanisms underlying superconductivity. Local measurements of penetration depths or magnetic stray fields enable access to fundamental aspects such as nanoscale variations in superfluid densities or the order parameter symmetry of superconductors. However, experimental tools that offer quantitative, nanoscale magnetometry and operate over large ranges of temperature and magnetic fields are still lacking. Here, we demonstrate the first operation of a cryogenic scanning quantum sensor in the form of a single nitrogen-vacancy electronic spin in diamond, which is capable of overcoming these existing limitations. To demonstrate the power of our approach, we perform quantitative, nanoscale magnetic imaging of Pearl vortices in the cuprate superconductor YBa2Cu3O7-δ. With a sensor-to-sample distance of ∼10 nm, we observe striking deviations from the prevalent monopole approximation in our vortex stray-field images, and find excellent quantitative agreement with Pearl's analytic model. Our experiments provide a non-invasive and unambiguous determination of the system's local penetration depth and are readily extended to higher temperatures and magnetic fields. These results demonstrate the potential of quantitative quantum sensors in benchmarking microscopic models of complex electronic systems and open the door for further exploration of strongly correlated electron physics using scanning nitrogen-vacancy magnetometry.

  14. Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy

    Science.gov (United States)

    Wang, Yu; Kang, Soyoung; Khan, Altaz; Ruttner, Gabriel; Leigh, Steven Y.; Murray, Melissa; Abeytunge, Sanjee; Peterson, Gary; Rajadhyaksha, Milind; Dintzis, Suzanne; Javid, Sara; Liu, Jonathan T. C.

    2016-02-01

    There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast-conserving surgeries.

  15. Three Dimensional Molecular Imaging for Lignocellulosic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W.; Sweedler, Jonathan V.

    2011-06-09

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

  16. NAOMI: nanoparticle-assisted optical molecular imaging

    Science.gov (United States)

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

    2007-02-01

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

  17. Molecular Ultrasound Imaging for the Detection of Neural Inflammation

    Science.gov (United States)

    Volz, Kevin R.

    performed while targeting three early inflammatory markers (P-selectin, VCAM-1, ICAM-1). Imaging protocols and outcome measures of previous TCEUS investigations of inflammation were replicated to aid in comparisons of outcomes. Signal intensity data was used to generate time intensity curves for qualitative and quantitative analysis of contrast agent temporal behavior. A proof of principle study established preclinical evidence to support the ability of TCEUS to detect acute neural inflammation. Substantial increases in signal intensities were observed while targeting inflammatory markers compared to controls. Further investigations consisted of examining molecular ultrasound sensitivity, and were accomplished by examining targeted contrast agent dosing parameters, and the ability of TCEUS to longitudinally evaluate neural inflammation. Qualitative analysis of TCEUS imaging performed with both administered doses revealed marked increases in signal intensities during acute inflammation, where inflammatory marker expression was presumably at its highest. This was in comparison to measures obtained in the absence of, and during, chronic inflammation. This research contributes much needed empirical evidence to the molecular ultrasound body of literature, and represents the first steps towards advancing this TCEUS application to clinical practice. Future studies are necessary to further these findings and effectively build upon this evidence. Increasing evidence of TCEUS use for the detection of neural inflammation will aid in its eventual clinical translation, where it will likely have a positive impact on patient care.

  18. DESCIFRANDO LAS BASES MOLECULARES DE LA RESISTENCIA CUANTITATIVA Deciphering the Molecular Bases of Quantitative Resistance

    Directory of Open Access Journals (Sweden)

    CAMILO LÓPEZ

    2011-08-01

    Full Text Available Uno de los factores que más afectan los cultivos son las enfermedades ocasionadas por patógenos. La resistencia vegetal ha sido clásicamente dividida en dos tipos: i completa, vertical o cualitativa que es gobernada por un solo gen e ii incompleta, horizontal o cuantitativa la cual es gobernada por varios genes. Aunque la resistencia cuantitativa provee resistencia de amplio espectro y es durable, los mecanismos moleculares subyacentes no han sido estudiados en detalle. En esta revisión se propone un modelo basado en co-localización de genes similares a los genes clásicos de resistencia cualitativa con QTLs (Quantitative Trait Loci para explicar el mecanismo involucrado en el reconocimiento del patógeno durante la resistencia cuantitativa. Además se presenta información acerca del progreso obtenido en los últimos tres años para entender este tipo de resistencia, lo que culminó con la clonación de varios genes asociados a resistencia cuantitativa. En conjunto, estos datos proveen nuevas luces sobre la naturaleza genética de este tipo de resistencia y de cómo puede ser empleada en programas de mejoramiento genético.Plant pathogens are some of the most important factors affecting crop production. Classically two general types of plant resistance to pathogens have been recognized: i complete, vertical or qualitative resistance governed by a single gene; and ii incomplete, horizontal or quantitative resistance, which is governed by several genes. Although quantitative resistance provides broad spectrum and more durable resistance, the underlying molecular mechanism involved in pathogen recognition has not been deeply studied. In this review, we proposed a model to explain the molecular mechanism involved in the pathogen recognition during the quantitative resistance. This is based on the co-localization of similar classical qualitative resistance genes with QTL (Quantitative Trait Loci. In addition, information is presented about the

  19. Quantitative 7T phase imaging in premanifest Huntington disease.

    Science.gov (United States)

    Apple, A C; Possin, K L; Satris, G; Johnson, E; Lupo, J M; Jakary, A; Wong, K; Kelley, D A C; Kang, G A; Sha, S J; Kramer, J H; Geschwind, M D; Nelson, S J; Hess, C P

    2014-09-01

    In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease. © 2014 by American Journal of Neuroradiology.

  20. Molecular orbital imaging for partially aligned molecules

    Science.gov (United States)

    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.

  1. Carbohydrates and phenols as quantitative molecular vegetation proxies in peats

    Science.gov (United States)

    Kaiser, K.; Benner, R. H.

    2012-12-01

    Vegetation in peatlands is intricately linked to local environmental conditions and climate. Here we use chemical analyses of carbohydrates and phenols to reconstruct paleovegetation in peat cores collected from 56.8°N (SIB04), 58.4°N (SIB06), 63.8°N (G137) and 66.5°N (E113) in the Western Siberian Lowland. Lignin phenols (vanillyl and syringyl phenols) were sensitive biomarkers for vascular plant contributions and provided additional information on the relative contributions of angiosperm and gymnosperm plants. Specific neutral sugar compositions allowed identification of sphagnum mosses, sedges (Cyperaceae) and lichens. Hydroxyphenols released by CuO oxidation were useful tracers of sphagnum moss contributions. The three independent molecular proxies were calibrated with a diverse group of peat-forming plants to yield quantitative estimates (%C) of vascular plant, sphagnum moss and lichen contributions in peat core samples. Correlation analysis indicated the three molecular proxies produced fairly similar results for paleovegetation compositions, generally within the error interval of each approach (≤26%). The lignin-based method generally lead to higher estimates of vascular plant vegetation. Several significant deviations were also observed due to different reactivities of carbohydrate and phenolic polymers during peat decomposition. Rapid vegetation changes on timescales of 50-200 years were observed in the southern cores SIB04 and SIB06 over the last 2000 years. Vanillyl and syringyl phenol ratios indicated these vegetation changes were largely due to varying inputs of angiosperm and gymnosperm plants. The northern permafrost cores G137 and E113 showed a more stable development. Lichens briefly replaced sphagnum mosses and vascular plants in both of these cores. Shifts in vegetation did not correlate well with Northern hemisphere climate variability over the last 2000 years. This suggested that direct climate forcing of peatland dynamics was overridden

  2. Motion tracking in infrared imaging for quantitative medical diagnostic applications

    Science.gov (United States)

    Cheng, Tze-Yuan; Herman, Cila

    2014-01-01

    In medical applications, infrared (IR) thermography is used to detect and examine the thermal signature of skin abnormalities by quantitatively analyzing skin temperature in steady state conditions or its evolution over time, captured in an image sequence. However, during the image acquisition period, the involuntary movements of the patient are unavoidable, and such movements will undermine the accuracy of temperature measurement for any particular location on the skin. In this study, a tracking approach using a template-based algorithm is proposed, to follow the involuntary motion of the subject in the IR image sequence. The motion tacking will allow to associate a temperature evolution to each spatial location on the body while the body moves relative to the image frame. The affine transformation model is adopted to estimate the motion parameters of the template image. The Lucas-Kanade algorithm is applied to search for the optimized parameters of the affine transformation. A weighting mask is incorporated into the algorithm to ensure its tracking robustness. To evaluate the feasibility of the tracking approach, two sets of IR image sequences with random in-plane motion were tested in our experiments. A steady-state (no heating or cooling) IR image sequence in which the skin temperature is in equilibrium with the environment was considered first. The thermal recovery IR image sequence, acquired when the skin is recovering from 60-s cooling, was the second case analyzed. By proper selection of the template image along with template update, satisfactory tracking results were obtained for both IR image sequences. The achieved tracking accuracies are promising in terms of satisfying the demands imposed by clinical applications of IR thermography.

  3. PCA-based groupwise image registration for quantitative MRI.

    Science.gov (United States)

    Huizinga, W; Poot, D H J; Guyader, J-M; Klaassen, R; Coolen, B F; van Kranenburg, M; van Geuns, R J M; Uitterdijk, A; Polfliet, M; Vandemeulebroucke, J; Leemans, A; Niessen, W J; Klein, S

    2016-04-01

    Quantitative magnetic resonance imaging (qMRI) is a technique for estimating quantitative tissue properties, such as the T1 and T2 relaxation times, apparent diffusion coefficient (ADC), and various perfusion measures. This estimation is achieved by acquiring multiple images with different acquisition parameters (or at multiple time points after injection of a contrast agent) and by fitting a qMRI signal model to the image intensities. Image registration is often necessary to compensate for misalignments due to subject motion and/or geometric distortions caused by the acquisition. However, large differences in image appearance make accurate image registration challenging. In this work, we propose a groupwise image registration method for compensating misalignment in qMRI. The groupwise formulation of the method eliminates the requirement of choosing a reference image, thus avoiding a registration bias. The method minimizes a cost function that is based on principal component analysis (PCA), exploiting the fact that intensity changes in qMRI can be described by a low-dimensional signal model, but not requiring knowledge on the specific acquisition model. The method was evaluated on 4D CT data of the lungs, and both real and synthetic images of five different qMRI applications: T1 mapping in a porcine heart, combined T1 and T2 mapping in carotid arteries, ADC mapping in the abdomen, diffusion tensor mapping in the brain, and dynamic contrast-enhanced mapping in the abdomen. Each application is based on a different acquisition model. The method is compared to a mutual information-based pairwise registration method and four other state-of-the-art groupwise registration methods. Registration accuracy is evaluated in terms of the precision of the estimated qMRI parameters, overlap of segmented structures, distance between corresponding landmarks, and smoothness of the deformation. In all qMRI applications the proposed method performed better than or equally well as

  4. Image based quantitative reader for Lateral flow immunofluorescence assay.

    Science.gov (United States)

    Chowdhury, Kaushik Basak; Joseph, Jayaraj; Sivaprakasam, Mohanasankar

    2015-08-01

    Fluorescence Lateral flow immunoassays (LFIA) have wide range of applications in point-of-care testing (POCT). An integrated, motion-free, accurate, reliable reader that performs automated quantitative analysis of LFIA is essential for POCT diagnosis. We demonstrate an image based quantitative method to read the lateral flow immunofluorescence test strips. The developed reader uses line laser diode module to illuminate the LFIA test strip having fluorescent dye. Fluorescence light coming from the region of interest (ROI) of the LFIA test strip was filtered using an emission filter and imaged using a camera following which images were processed in computer. A dedicated control program was developed that automated the entire process including illumination of the test strip using laser diode, capturing the ROI of the test strip, processing and analyzing the images and displaying of results. Reproducibility of the reader has been evaluated using few reference cartridges and HbA1c (Glycated haemoglobin) test cartridges. The proposed system can be upgraded to a compact reader for widespread testing of LFIA test strips.

  5. Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging

    Science.gov (United States)

    Swales, John G.; Strittmatter, Nicole; Tucker, James W.; Clench, Malcolm R.; Webborn, Peter J. H.; Goodwin, Richard J. A.

    2016-11-01

    Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

  6. Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

    Science.gov (United States)

    Swales, John G; Strittmatter, Nicole; Tucker, James W; Clench, Malcolm R; Webborn, Peter J H; Goodwin, Richard J A

    2016-11-24

    Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

  7. Quantitative perfusion imaging in magnetic resonance imaging; Quantitative Perfusionsbildgebung in der Magnetresonanztomographie

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, F.G.; Gaa, T.; Zimmer, F. [Universitaet Heidelberg, Computerunterstuetzte Klinische Medizin, Medizinische Fakultaet Mannheim, Mannheim (Germany); Ong, M.M.; Riffel, P.; Hausmann, D.; Schoenberg, S.O.; Weis, M. [Universitaet Heidelberg, Institut fuer Klinische Radiologie und Nuklearmedizin, Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim, Mannheim (Germany)

    2016-02-15

    Magnetic resonance imaging (MRI) is recognized for its superior tissue contrast while being non-invasive and free of ionizing radiation. Due to the development of new scanner hardware and fast imaging techniques during the last decades, access to tissue and organ functions became possible. One of these functional imaging techniques is perfusion imaging with which tissue perfusion and capillary permeability can be determined from dynamic imaging data. Perfusion imaging by MRI can be performed by two approaches, arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE) MRI. While the first method uses magnetically labelled water protons in arterial blood as an endogenous tracer, the latter involves the injection of a contrast agent, usually gadolinium (Gd), as a tracer for calculating hemodynamic parameters. Studies have demonstrated the potential of perfusion MRI for diagnostics and also for therapy monitoring. The utilization and application of perfusion MRI are still restricted to specialized centers, such as university hospitals. A broad application of the technique has not yet been implemented. The MRI perfusion technique is a valuable tool that might come broadly available after implementation of standards on European and international levels. Such efforts are being promoted by the respective professional bodies. (orig.) [German] Die Magnetresonanztomographie (MRT) zeichnet sich durch einen ueberlegenen Gewebekontrast aus, waehrend sie nichtinvasiv und frei von ionisierender Strahlung ist. Sie bietet Zugang zu Gewebe- und Organfunktion. Eine dieser funktionellen bildgebenden Verfahren ist die Perfusionsbildgebung. Mit dieser Technik koennen u. a. Gewebeperfusion und Kapillarpermeabilitaet aus dynamischen Bilddaten bestimmt werden. Perfusionsbildgebung mithilfe der MRT kann durch 2 Ansaetze, naemlich ''arterial spin labeling'' (ASL) und dynamische kontrastverstaerkte (DCE-)MRT durchgefuehrt werden. Waehrend die erste Methode magnetisch

  8. Quantitative imaging of heterogeneous dynamics in drying and aging paints.

    Science.gov (United States)

    van der Kooij, Hanne M; Fokkink, Remco; van der Gucht, Jasper; Sprakel, Joris

    2016-09-29

    Drying and aging paint dispersions display a wealth of complex phenomena that make their study fascinating yet challenging. To meet the growing demand for sustainable, high-quality paints, it is essential to unravel the microscopic mechanisms underlying these phenomena. Visualising the governing dynamics is, however, intrinsically difficult because the dynamics are typically heterogeneous and span a wide range of time scales. Moreover, the high turbidity of paints precludes conventional imaging techniques from reaching deep inside the paint. To address these challenges, we apply a scattering technique, Laser Speckle Imaging, as a versatile and quantitative tool to elucidate the internal dynamics, with microscopic resolution and spanning seven decades of time. We present a toolbox of data analysis and image processing methods that allows a tailored investigation of virtually any turbid dispersion, regardless of the geometry and substrate. Using these tools we watch a variety of paints dry and age with unprecedented detail.

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

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-06-01

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

  10. Central benzodiazepine receptor imaging and quantitation with single photon emission computerised tomography

    DEFF Research Database (Denmark)

    Okocha, C I; Kapczinski, F; Lassen, N

    1995-01-01

    This review discusses the current use of single photon emission computerised tomography (SPECT) for central benzodiazepine receptor imaging and quantitation. The general principles underlying SPECT imaging and receptor quantitation methods such as the kinetic, pseudo-equilibrium and steady...

  11. Mri: Selected Topics in Quantitation and Image Processing.

    Science.gov (United States)

    Yi, Yun

    1990-10-01

    This research has focused on four areas of MRI with the objectives being a critical evaluation of the factors both visually and instrumentation that effect the quantitative indices of MRI. The following four areas of MRI were investigated:. Project #1. In both of the r.f. transmitter and receiver, many non-linearities exist which produce image distortions and loss of quantitative information. Key factors in spin echo (SE) imaging involve phase and gain adjustment of the quadrature phase detectors. To compensate for these nonlinearities, NMR spectroscopist developed techniques involving phase rolling of the rf pulses for dealing with one dimensional spectra. In this project, the effect of these nonlinearities were investigated for MR imaging on a 2.0T small bore system in respect to image uniformity and artifacts. Project #2. In the presence of surface coils, image artifacts are generated which oftentimes produce large signal intensities and suppress the image gray scale in clinically useful regions. In this study, eight image renormalization algorithms were evaluated for their effects on image contrast, suppression of artifacts, and texture. In addition, images were evaluated independently by four radiologists. Project #3. The use of MRI to follow and characterize serial changes in vertebral marrow, as a function of therapy, age or sex, has produced inconsistent results. Systematic examinations were made of the effects of RF tuning and tip angles as well as RF coil response on both T1 and T2 relaxation times. Using calibration phantoms, algorithms were developed which reduce the instrumental variation in MR signal to less than 10% from the cervical (C7) to the lumbar (L2) vertebral bodies. These algorithms were evaluated by use of serial MRI on volunteers and a few patients receiving radiation therapy (RT) of the chest and abdomen for lymphoma. Project #4. Evaluation of sensitivity of chemical shift RF pulse sequences for water/lipid separation were evaluated on a

  12. An approach for quantitative image quality analysis for CT

    Science.gov (United States)

    Rahimi, Amir; Cochran, Joe; Mooney, Doug; Regensburger, Joe

    2016-03-01

    An objective and standardized approach to assess image quality of Compute Tomography (CT) systems is required in a wide variety of imaging processes to identify CT systems appropriate for a given application. We present an overview of the framework we have developed to help standardize and to objectively assess CT image quality for different models of CT scanners used for security applications. Within this framework, we have developed methods to quantitatively measure metrics that should correlate with feature identification, detection accuracy and precision, and image registration capabilities of CT machines and to identify strengths and weaknesses in different CT imaging technologies in transportation security. To that end we have designed, developed and constructed phantoms that allow for systematic and repeatable measurements of roughly 88 image quality metrics, representing modulation transfer function, noise equivalent quanta, noise power spectra, slice sensitivity profiles, streak artifacts, CT number uniformity, CT number consistency, object length accuracy, CT number path length consistency, and object registration. Furthermore, we have developed a sophisticated MATLAB based image analysis tool kit to analyze CT generated images of phantoms and report these metrics in a format that is standardized across the considered models of CT scanners, allowing for comparative image quality analysis within a CT model or between different CT models. In addition, we have developed a modified sparse principal component analysis (SPCA) method to generate a modified set of PCA components as compared to the standard principal component analysis (PCA) with sparse loadings in conjunction with Hotelling T2 statistical analysis method to compare, qualify, and detect faults in the tested systems.

  13. Automatic quantitative analysis of cardiac MR perfusion images

    Science.gov (United States)

    Breeuwer, Marcel M.; Spreeuwers, Luuk J.; Quist, Marcel J.

    2001-07-01

    Magnetic Resonance Imaging (MRI) is a powerful technique for imaging cardiovascular diseases. The introduction of cardiovascular MRI into clinical practice is however hampered by the lack of efficient and accurate image analysis methods. This paper focuses on the evaluation of blood perfusion in the myocardium (the heart muscle) from MR images, using contrast-enhanced ECG-triggered MRI. We have developed an automatic quantitative analysis method, which works as follows. First, image registration is used to compensate for translation and rotation of the myocardium over time. Next, the boundaries of the myocardium are detected and for each position within the myocardium a time-intensity profile is constructed. The time interval during which the contrast agent passes for the first time through the left ventricle and the myocardium is detected and various parameters are measured from the time-intensity profiles in this interval. The measured parameters are visualized as color overlays on the original images. Analysis results are stored, so that they can later on be compared for different stress levels of the heart. The method is described in detail in this paper and preliminary validation results are presented.

  14. Combining PALM and SOFI for quantitative imaging of focal adhesions in living cells

    Science.gov (United States)

    Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Feletti, Lely; Lasser, Theo; Radenovic, Aleksandra

    2017-02-01

    Focal adhesions are complicated assemblies of hundreds of proteins that allow cells to sense their extracellular matrix and adhere to it. Although most focal adhesion proteins have been identified, their spatial organization in living cells remains challenging to observe. Photo-activated localization microscopy (PALM) is an interesting technique for this purpose, especially since it allows estimation of molecular parameters such as the number of fluorophores. However, focal adhesions are dynamic entities, requiring a temporal resolution below one minute, which is difficult to achieve with PALM. In order to address this problem, we merged PALM with super-resolution optical fluctuation imaging (SOFI) by applying both techniques to the same data. Since SOFI tolerates an overlap of single molecule images, it can improve the temporal resolution compared to PALM. Moreover, an adaptation called balanced SOFI (bSOFI) allows estimation of molecular parameters, such as the fluorophore density. We therefore performed simulations in order to assess PALM and SOFI for quantitative imaging of dynamic structures. We demonstrated the potential of our PALM-SOFI concept as a quantitative imaging framework by investigating moving focal adhesions in living cells.

  15. Quantitative magnetic resonance imaging of cortical multiple sclerosis pathology

    DEFF Research Database (Denmark)

    Tardif, Christine L; Bedell, Barry J; Eskildsen, Simon Fristed

    2012-01-01

    pathology. The objective of this study was to characterize the MRI signature of CLs to help interpret the changes seen in vivo and elucidate the factors limiting their visualization. A quantitative 3D high-resolution (350 μm isotropic) MRI study at 3 Tesla of a fixed post mortem cerebral hemisphere from......Although significant improvements have been made regarding the visualization and characterization of cortical multiple sclerosis (MS) lesions using magnetic resonance imaging (MRI), cortical lesions (CL) continue to be under-detected in vivo, and we have a limited understanding of the causes of GM...... a patient with MS is presented in combination with matched immunohistochemistry. Type III subpial lesions are characterized by an increase in T1, T2 and M0, and a decrease in MTR in comparison to the normal appearing cortex (NAC). All quantitative MR parameters were associated with cortical GM myelin...

  16. Quantitative Determination of Ceramide Molecular Species in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Samar Al Makdessi

    2016-09-01

    Full Text Available Background/Aims: The activation of acid sphingomyelinase by cellular stress or receptors or the de novo synthesis lead to the formation of ceramide (N-acylsphingosine, which in turn modifies the biophysical properties of cellular membrane and greatly amplifies the intensity of the initial signal. Ceramide, which acts by re-organizing a given signalosome rather than being a second messenger, has many functions in infection biology, cancer, cardiovascular syndromes, and immune regulation. Experimental studies on the infection of human cells with different bacterial agents demonstrated the activation of the acid sphingomyelinase/ceramide system. Moreover, the release of ceramide was found to be a requisite for the uptake of the pathogen. Considering the particular importance of the cellular role of ceramide, it was necessary to develop sensitive and accurate methods for its quantification. Methods: Here, we describe a method quantifying ceramide in dendritic cells and defining the different fatty acids (FA bound to sphingosine. The main steps of the method include extraction of total lipids, separation of the ceramide by thin-layer chromatography, derivatization of ceramide-fatty acids (Cer-FA, and quantitation of these acids in their methyl form by gas chromatography on polar capillary columns. The identification of FA was achieved by means of known standards and confirmed by mass spectrometry. Results: FA ranging between C10 and C24 could be detected and quantified. The concentration of the sum of Cer-FA amounted to 14.88 ± 8.98 nmol/106 cells (n=10. Oleic acid, which accounted for approximately half of Cer-FA (7.73 ± 6.52 nmol/106 cells was the predominant fatty acid followed by palmitic acid (3.47 ± 1.54 nmol/106 cells. Conclusion: This highly sensitive method allows the quantification of different molecular species of ceramides.

  17. Quantitative Assessment of Molecular Dynamics Sampling for Flexible Systems.

    Science.gov (United States)

    Nemec, Mike; Hoffmann, Daniel

    2017-02-14

    Molecular dynamics (MD) simulation is a natural method for the study of flexible molecules but at the same time is limited by the large size of the conformational space of these molecules. We ask by how much the MD sampling quality for flexible molecules can be improved by two means: the use of diverse sets of trajectories starting from different initial conformations to detect deviations between samples and sampling with enhanced methods such as accelerated MD (aMD) or scaled MD (sMD) that distort the energy landscape in controlled ways. To this end, we test the effects of these approaches on MD simulations of two flexible biomolecules in aqueous solution, Met-Enkephalin (5 amino acids) and HIV-1 gp120 V3 (a cycle of 35 amino acids). We assess the convergence of the sampling quantitatively with known, extensive measures of cluster number Nc and cluster distribution entropy Sc and with two new quantities, conformational overlap Oconf and density overlap Odens, both conveniently ranging from 0 to 1. These new overlap measures quantify self-consistency of sampling in multitrajectory MD experiments, a necessary condition for converged sampling. A comprehensive assessment of sampling quality of MD experiments identifies the combination of diverse trajectory sets and aMD as the most efficient approach among those tested. However, analysis of Odens between conventional and aMD trajectories also reveals that we have not completely corrected aMD sampling for the distorted energy landscape. Moreover, for V3, the courses of Nc and Odens indicate that much higher resources than those generally invested today will probably be needed to achieve convergence. The comparative analysis also shows that conventional MD simulations with insufficient sampling can be easily misinterpreted as being converged.

  18. Quantitative damage imaging using Lamb wave diffraction tomography

    Science.gov (United States)

    Zhang, Hai-Yan; Ruan, Min; Zhu, Wen-Fa; Chai, Xiao-Dong

    2016-12-01

    In this paper, we investigate the diffraction tomography for quantitative imaging damages of partly through-thickness holes with various shapes in isotropic plates by using converted and non-converted scattered Lamb waves generated numerically. Finite element simulations are carried out to provide the scattered wave data. The validity of the finite element model is confirmed by the comparison of scattering directivity pattern (SDP) of circle blind hole damage between the finite element simulations and the analytical results. The imaging method is based on a theoretical relation between the one-dimensional (1D) Fourier transform of the scattered projection and two-dimensional (2D) spatial Fourier transform of the scattering object. A quantitative image of the damage is obtained by carrying out the 2D inverse Fourier transform of the scattering object. The proposed approach employs a circle transducer network containing forward and backward projections, which lead to so-called transmission mode (TMDT) and reflection mode diffraction tomography (RMDT), respectively. The reconstructed results of the two projections for a non-converted S0 scattered mode are investigated to illuminate the influence of the scattering field data. The results show that Lamb wave diffraction tomography using the combination of TMDT and RMDT improves the imaging effect compared with by using only the TMDT or RMDT. The scattered data of the converted A0 mode are also used to assess the performance of the diffraction tomography method. It is found that the circle and elliptical shaped damages can still be reasonably identified from the reconstructed images while the reconstructed results of other complex shaped damages like crisscross rectangles and racecourse are relatively poor. Project supported by the National Natural Science Foundation of China (Grant Nos. 11474195, 11274226, 11674214, and 51478258).

  19. Quantitative measure in image segmentation for skin lesion images: A preliminary study

    Science.gov (United States)

    Azmi, Nurulhuda Firdaus Mohd; Ibrahim, Mohd Hakimi Aiman; Keng, Lau Hui; Ibrahim, Nuzulha Khilwani; Sarkan, Haslina Md

    2014-12-01

    Automatic Skin Lesion Diagnosis (ASLD) allows skin lesion diagnosis by using a computer or mobile devices. The idea of using a computer to assist in diagnosis of skin lesions was first proposed in the literature around 1985. Images of skin lesions are analyzed by the computer to capture certain features thought to be characteristic of skin diseases. These features (expressed as numeric values) are then used to classify the image and report a diagnosis. Image segmentation is often a critical step in image analysis and it may use statistical classification, thresholding, edge detection, region detection, or any combination of these techniques. Nevertheless, image segmentation of skin lesion images is yet limited to superficial evaluations which merely display images of the segmentation results and appeal to the reader's intuition for evaluation. There is a consistent lack of quantitative measure, thus, it is difficult to know which segmentation present useful results and in which situations they do so. If segmentation is done well, then, all other stages in image analysis are made simpler. If significant features (that are crucial for diagnosis) are not extracted from images, it will affect the accuracy of the automated diagnosis. This paper explore the existing quantitative measure in image segmentation ranging in the application of pattern recognition for example hand writing, plat number, and colour. Selecting the most suitable segmentation measure is highly important so that as much relevant features can be identified and extracted.

  20. Quantitative volumetric Raman imaging of three dimensional cell cultures

    Science.gov (United States)

    Kallepitis, Charalambos; Bergholt, Mads S.; Mazo, Manuel M.; Leonardo, Vincent; Skaalure, Stacey C.; Maynard, Stephanie A.; Stevens, Molly M.

    2017-03-01

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  1. Quantitative blood flow velocity imaging using laser speckle flowmetry

    Science.gov (United States)

    Nadort, Annemarie; Kalkman, Koen; van Leeuwen, Ton G.; Faber, Dirk J.

    2016-04-01

    Laser speckle flowmetry suffers from a debated quantification of the inverse relation between decorrelation time (τc) and blood flow velocity (V), i.e. 1/τc = αV. Using a modified microcirculation imager (integrated sidestream dark field - laser speckle contrast imaging [SDF-LSCI]), we experimentally investigate on the influence of the optical properties of scatterers on α in vitro and in vivo. We found a good agreement to theoretical predictions within certain limits for scatterer size and multiple scattering. We present a practical model-based scaling factor to correct for multiple scattering in microcirculatory vessels. Our results show that SDF-LSCI offers a quantitative measure of flow velocity in addition to vessel morphology, enabling the quantification of the clinically relevant blood flow, velocity and tissue perfusion.

  2. High-resolution quantitative imaging of the substantia nigra.

    Science.gov (United States)

    Trujillo, Paula; Smith, Alex K; Summers, Paul E; Mainardi, Luca M; Cerutti, Sergio; Smith, Seth A; Costa, Antonella

    2015-01-01

    There is a growing interest in identifying neuroimaging-based biomarkers for Parkinson's disease (PD), a progressive neurodegenerative disorder in which the major pathologic substrate is the loss of pigmented dopaminergic neurons in the substantia nigra (SN). Recently, an MRI technique dubbed "neuromelanin-sensitive MRI" (NM-MRI), has been found to provide notable contrast between the SN and surrounding brain tissues with potential applications as biomarker of PD. The contrast in NM-MRI has been associated with magnetization transfer (MT) effects, and thus the goal of this study was to characterize the impact of MT on NM-MRI, and to demonstrate the feasibility of performing quantitative MT (qMT) imaging in human SN. The results of this study demonstrate that high-resolution rapid qMT imaging of the SN can be reliably obtained within reasonable scan times, thereby can be translatable into clinical practice.

  3. Quantitative image analysis of WE43-T6 cracking behavior

    Science.gov (United States)

    Ahmad, A.; Yahya, Z.

    2013-06-01

    Environment-assisted cracking of WE43 cast magnesium (4.2 wt.% Yt, 2.3 wt.% Nd, 0.7% Zr, 0.8% HRE) in the T6 peak-aged condition was induced in ambient air in notched specimens. The mechanism of fracture was studied using electron backscatter diffraction, serial sectioning and in situ observations of crack propagation. The intermetallic (rare earthed-enriched divorced intermetallic retained at grain boundaries and predominantly at triple points) material was found to play a significant role in initiating cracks which leads to failure of this material. Quantitative measurements were required for this project. The populations of the intermetallic and clusters of intermetallic particles were analyzed using image analysis of metallographic images. This is part of the work to generate a theoretical model of the effect of notch geometry on the static fatigue strength of this material.

  4. Quantitative volumetric Raman imaging of three dimensional cell cultures

    KAUST Repository

    Kallepitis, Charalambos

    2017-03-22

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell–material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  5. Radiolabeled nanogels for nuclear molecular imaging.

    Science.gov (United States)

    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.

  6. A Novel Image Cytometric Method for Quantitation of Immunohistochemical Staining of Cytoplasmic Antigens

    Directory of Open Access Journals (Sweden)

    M. Guillaud

    1997-01-01

    Full Text Available Evaluation of molecular markers by immunohistochemical labelling of tissue sections has traditionally been performed by qualitative assessment by trained pathologists. For those markers with a staining component present outside of the nucleus, there has been no image histometric method available to reliably and consistently define cell interfaces within the tissue. We present a new method of approximating cellular boundaries to define cellular regions within which quantitative measurements of staining intensity may be made. The method is based upon Voronoi tessellation of a defined region of interest (ROI, and requires only the position of the nuclear centroids within the ROI.

  7. Quantitative analysis of brain magnetic resonance imaging for hepatic encephalopathy

    Science.gov (United States)

    Syh, Hon-Wei; Chu, Wei-Kom; Ong, Chin-Sing

    1992-06-01

    High intensity lesions around ventricles have recently been observed in T1-weighted brain magnetic resonance images for patients suffering hepatic encephalopathy. The exact etiology that causes magnetic resonance imaging (MRI) gray scale changes has not been totally understood. The objective of our study was to investigate, through quantitative means, (1) the amount of changes to brain white matter due to the disease process, and (2) the extent and distribution of these high intensity lesions, since it is believed that the abnormality may not be entirely limited to the white matter only. Eleven patients with proven haptic encephalopathy and three normal persons without any evidence of liver abnormality constituted our current data base. Trans-axial, sagittal, and coronal brain MRI were obtained on a 1.5 Tesla scanner. All processing was carried out on a microcomputer-based image analysis system in an off-line manner. Histograms were decomposed into regular brain tissues and lesions. Gray scale ranges coded as lesion were then brought back to original images to identify distribution of abnormality. Our results indicated the disease process involved pallidus, mesencephalon, and subthalamic regions.

  8. A Quantitative Method for Microtubule Analysis in Fluorescence Images.

    Science.gov (United States)

    Lan, Xiaodong; Li, Lingfei; Hu, Jiongyu; Zhang, Qiong; Dang, Yongming; Huang, Yuesheng

    2015-12-01

    Microtubule analysis is of significant value for a better understanding of normal and pathological cellular processes. Although immunofluorescence microscopic techniques have proven useful in the study of microtubules, comparative results commonly rely on a descriptive and subjective visual analysis. We developed an objective and quantitative method based on image processing and analysis of fluorescently labeled microtubular patterns in cultured cells. We used a multi-parameter approach by analyzing four quantifiable characteristics to compose our quantitative feature set. Then we interpreted specific changes in the parameters and revealed the contribution of each feature set using principal component analysis. In addition, we verified that different treatment groups could be clearly discriminated using principal components of the multi-parameter model. High predictive accuracy of four commonly used multi-classification methods confirmed our method. These results demonstrated the effectiveness and efficiency of our method in the analysis of microtubules in fluorescence images. Application of the analytical methods presented here provides information concerning the organization and modification of microtubules, and could aid in the further understanding of structural and functional aspects of microtubules under normal and pathological conditions.

  9. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    Directory of Open Access Journals (Sweden)

    Ahmed R

    2014-03-01

    Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

  10. Quantitative MRI radiomics in the prediction of molecular classifications of breast cancer subtypes in the TCGA/TCIA data set.

    Science.gov (United States)

    Li, Hui; Zhu, Yitan; Burnside, Elizabeth S; Huang, Erich; Drukker, Karen; Hoadley, Katherine A; Fan, Cheng; Conzen, Suzanne D; Zuley, Margarita; Net, Jose M; Sutton, Elizabeth; Whitman, Gary J; Morris, Elizabeth; Perou, Charles M; Ji, Yuan; Giger, Maryellen L

    2016-01-01

    Using quantitative radiomics, we demonstrate that computer-extracted magnetic resonance (MR) image-based tumor phenotypes can be predictive of the molecular classification of invasive breast cancers. Radiomics analysis was performed on 91 MRIs of biopsy-proven invasive breast cancers from National Cancer Institute's multi-institutional TCGA/TCIA. Immunohistochemistry molecular classification was performed including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and for 84 cases, the molecular subtype (normal-like, luminal A, luminal B, HER2-enriched, and basal-like). Computerized quantitative image analysis included: three-dimensional lesion segmentation, phenotype extraction, and leave-one-case-out cross validation involving stepwise feature selection and linear discriminant analysis. The performance of the classifier model for molecular subtyping was evaluated using receiver operating characteristic analysis. The computer-extracted tumor phenotypes were able to distinguish between molecular prognostic indicators; area under the ROC curve values of 0.89, 0.69, 0.65, and 0.67 in the tasks of distinguishing between ER+ versus ER-, PR+ versus PR-, HER2+ versus HER2-, and triple-negative versus others, respectively. Statistically significant associations between tumor phenotypes and receptor status were observed. More aggressive cancers are likely to be larger in size with more heterogeneity in their contrast enhancement. Even after controlling for tumor size, a statistically significant trend was observed within each size group (P = 0.04 for lesions ≤ 2 cm; P = 0.02 for lesions >2 to ≤5 cm) as with the entire data set (P-value = 0.006) for the relationship between enhancement texture (entropy) and molecular subtypes (normal-like, luminal A, luminal B, HER2-enriched, basal-like). In conclusion, computer-extracted image phenotypes show promise for high-throughput discrimination of breast cancer subtypes and may yield a

  11. Laboratory medicine for molecular imaging of atherosclerosis.

    Science.gov (United States)

    Mangge, Harald; Almer, Gunter; Stelzer, Ingeborg; Reininghaus, Eva; Prassl, Ruth

    2014-11-01

    Atherosclerotic plaques are the main cause of life threatening clinical endpoints like myocardial infarction and stroke. To prevent these endpoints, the improved early diagnosis and treatment of vulnerable atherosclerotic vascular lesions are essential. Although originally applied for anticancer treatment, recent advances have also showed the considerable potential of nanotechnology for atherosclerosis. Otherwise, one domain of laboratory medicine is the investigation of new biomarkers. Recent research activities have identified the usability of biomarker-targeted nanoparticles for molecular imaging and pharmacologic modification of vulnerable atherosclerotic lesions leading to myocardial infarction or stroke. These investigations have established a new research interface between laboratory medicine, nanotechnology, cardiology/neurology, and radiology. In this review, we discuss inflammatory pathophysiologic mechanisms and biomarkers associated with a vulnerable atherosclerotic plaque phenotype. Further, we will emphasize cardiovascular relevant functionalized nanoparticle biomarker constructs which were developed within the cooperation interface between Laboratory Medicine (anti-inflammatory biomarkers), Nano-Medicine (nanoparticle development), and Radiology (molecular imaging). Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Magnetic Resonance-based Motion Correction for Quantitative PET in Simultaneous PET-MR Imaging.

    Science.gov (United States)

    Rakvongthai, Yothin; El Fakhri, Georges

    2017-07-01

    Motion degrades image quality and quantitation of PET images, and is an obstacle to quantitative PET imaging. Simultaneous PET-MR offers a tool that can be used for correcting the motion in PET images by using anatomic information from MR imaging acquired concurrently. Motion correction can be performed by transforming a set of reconstructed PET images into the same frame or by incorporating the transformation into the system model and reconstructing the motion-corrected image. Several phantom and patient studies have validated that MR-based motion correction strategies have great promise for quantitative PET imaging in simultaneous PET-MR. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Qualitative and quantitative interpretation of SEM image using digital image processing.

    Science.gov (United States)

    Saladra, Dawid; Kopernik, Magdalena

    2016-10-01

    The aim of the this study is improvement of qualitative and quantitative analysis of scanning electron microscope micrographs by development of computer program, which enables automatic crack analysis of scanning electron microscopy (SEM) micrographs. Micromechanical tests of pneumatic ventricular assist devices result in a large number of micrographs. Therefore, the analysis must be automatic. Tests for athrombogenic titanium nitride/gold coatings deposited on polymeric substrates (Bionate II) are performed. These tests include microshear, microtension and fatigue analysis. Anisotropic surface defects observed in the SEM micrographs require support for qualitative and quantitative interpretation. Improvement of qualitative analysis of scanning electron microscope images was achieved by a set of computational tools that includes binarization, simplified expanding, expanding, simple image statistic thresholding, the filters Laplacian 1, and Laplacian 2, Otsu and reverse binarization. Several modifications of the known image processing techniques and combinations of the selected image processing techniques were applied. The introduced quantitative analysis of digital scanning electron microscope images enables computation of stereological parameters such as area, crack angle, crack length, and total crack length per unit area. This study also compares the functionality of the developed computer program of digital image processing with existing applications. The described pre- and postprocessing may be helpful in scanning electron microscopy and transmission electron microscopy surface investigations. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

  14. Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography.

    Science.gov (United States)

    Boitor, Radu; Sinjab, Faris; Strohbuecker, Stephanie; Sottile, Virginie; Notingher, Ioan

    2016-06-23

    Raman micro-spectroscopy (RMS) is a non-invasive technique for imaging live cells in vitro. However, obtaining quantitative molecular information from Raman spectra is difficult because the intensity of a Raman band is proportional to the number of molecules in the sampled volume, which depends on the local molecular concentration and the thickness of the cell. In order to understand these effects, we combined RMS with atomic force microscopy (AFM), a technique that can measure accurately the thickness profile of the cells. Solution-based calibration models for RNA and albumin were developed to create quantitative maps of RNA and proteins in individual fixed cells. The maps were built by applying the solution-based calibration models, based on partial least squares fitting (PLS), on raster-scan Raman maps, after accounting for the local cell height obtained from the AFM. We found that concentrations of RNA in the cytoplasm of mouse neuroprogenitor stem cells (NSCs) were as high as 25 ± 6 mg ml(-1), while proteins were distributed more uniformly and reached concentrations as high as ∼50 ± 12 mg ml(-1). The combined AFM-Raman datasets from fixed cells were also used to investigate potential improvements for normalization of Raman spectral maps. For all Raman maps of fixed cells (n = 10), we found a linear relationship between the scores corresponding to the first component (PC1) and the cell height profile obtained by AFM. We used PC1 scores to reconstruct the relative height profiles of independent cells (n = 10), and obtained correlation coefficients with AFM maps higher than 0.99. Using this normalization method, qualitative maps of RNA and protein were used to obtain concentrations for live NSCs. While this study demonstrates the potential of using AFM and RMS for measuring concentration maps for individual NSCs in vitro, further studies are required to establish the robustness of the normalization method based on principal component analysis when comparing

  15. Real time blood testing using quantitative phase imaging.

    Directory of Open Access Journals (Sweden)

    Hoa V Pham

    Full Text Available We demonstrate a real-time blood testing system that can provide remote diagnosis with minimal human intervention in economically challenged areas. Our instrument combines novel advances in label-free optical imaging with parallel computing. Specifically, we use quantitative phase imaging for extracting red blood cell morphology with nanoscale sensitivity and NVIDIA's CUDA programming language to perform real time cellular-level analysis. While the blood smear is translated through focus, our system is able to segment and analyze all the cells in the one megapixel field of view, at a rate of 40 frames/s. The variety of diagnostic parameters measured from each cell (e.g., surface area, sphericity, and minimum cylindrical diameter are currently not available with current state of the art clinical instruments. In addition, we show that our instrument correctly recovers the red blood cell volume distribution, as evidenced by the excellent agreement with the cell counter results obtained on normal patients and those with microcytic and macrocytic anemia. The final data outputted by our instrument represent arrays of numbers associated with these morphological parameters and not images. Thus, the memory necessary to store these data is of the order of kilobytes, which allows for their remote transmission via, for example, the cellular network. We envision that such a system will dramatically increase access for blood testing and furthermore, may pave the way to digital hematology.

  16. Quantitative phase imaging for cell culture quality control.

    Science.gov (United States)

    Kastl, Lena; Isbach, Michael; Dirksen, Dieter; Schnekenburger, Jürgen; Kemper, Björn

    2017-05-01

    The potential of quantitative phase imaging (QPI) with digital holographic microscopy (DHM) for quantification of cell culture quality was explored. Label-free QPI of detached single cells in suspension was performed by Michelson interferometer-based self-interference DHM. Two pancreatic tumor cell lines were chosen as cellular model and analyzed for refractive index, volume, and dry mass under varying culture conditions. Firstly, adequate cell numbers for reliable statistics were identified. Then, to characterize the performance and reproducibility of the method, we compared results from independently repeated measurements and quantified the cellular response to osmolality changes of the cell culture medium. Finally, it was demonstrated that the evaluation of QPI images allows the extraction of absolute cell parameters which are related to cell layer confluence states. In summary, the results show that QPI enables label-free imaging cytometry, which provides novel complementary integral biophysical data sets for sophisticated quantification of cell culture quality with minimized sample preparation. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  17. Multi-modality molecular imaging for gastric cancer research

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2011-07-01

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

  19. Polarization second harmonic generation microscopy provides quantitative enhanced molecular specificity for tissue diagnostics.

    Science.gov (United States)

    Kumar, Rajesh; Grønhaug, Kirsten M; Romijn, Elisabeth I; Finnøy, Andreas; Davies, Catharina L; Drogset, Jon O; Lilledahl, Magnus B

    2015-09-01

    Due to specific structural organization at the molecular level, several biomolecules (e.g., collagen, myosin etc.) which are strong generators of second harmonic generation (SHG) signals, exhibit unique responses depending on the polarization of the excitation light. By using the polarization second harmonic generation (p-SHG) technique, the values of the second order susceptibility components can be used to differentiate the types of molecule, which cannot be done by the use of a standard SHG intensity image. In this report we discuss how to implement p-SHG on a commercial multiphoton microscope and overcome potential artifacts in susceptibility (χ) image. Furthermore we explore the potential of p-SHG microscopy by applying the technique to different types of tissue in order to determine corresponding reference values of the ratio of second-order χ tensor elements. These values may be used as a bio-marker to detect any structural alterations in pathological tissue for diagnostic purposes. The SHG intensity image (red) in (a) shows the distribution of collagen fibers in ovary tissue but cannot determine the type of collagen fiber. However, the histogram distribution (b) for the values of the χ tensor element ratio can be used to quantitatively identify the types of collagen fibers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Three modality image registration of brain SPECT/CT and MR images for quantitative analysis of dopamine transporter imaging

    Science.gov (United States)

    Yamaguchi, Yuzuho; Takeda, Yuta; Hara, Takeshi; Zhou, Xiangrong; Matsusako, Masaki; Tanaka, Yuki; Hosoya, Kazuhiko; Nihei, Tsutomu; Katafuchi, Tetsuro; Fujita, Hiroshi

    2016-03-01

    Important features in Parkinson's disease (PD) are degenerations and losses of dopamine neurons in corpus striatum. 123I-FP-CIT can visualize activities of the dopamine neurons. The activity radio of background to corpus striatum is used for diagnosis of PD and Dementia with Lewy Bodies (DLB). The specific activity can be observed in the corpus striatum on SPECT images, but the location and the shape of the corpus striatum on SPECT images only are often lost because of the low uptake. In contrast, MR images can visualize the locations of the corpus striatum. The purpose of this study was to realize a quantitative image analysis for the SPECT images by using image registration technique with brain MR images that can determine the region of corpus striatum. In this study, the image fusion technique was used to fuse SPECT and MR images by intervening CT image taken by SPECT/CT. The mutual information (MI) for image registration between CT and MR images was used for the registration. Six SPECT/CT and four MR scans of phantom materials are taken by changing the direction. As the results of the image registrations, 16 of 24 combinations were registered within 1.3mm. By applying the approach to 32 clinical SPECT/CT and MR cases, all of the cases were registered within 0.86mm. In conclusions, our registration method has a potential in superimposing MR images on SPECT images.

  1. Quantitative description of electroluminescence images of polymer solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Seeland, Marco; Roesch, Roland; Hoppe, Harald [Institute of Physics, Ilmenau University of Technology, Ilmenau (Germany)

    2011-07-01

    We present a quantitative description of electroluminescence images obtained on organic solar cells, which is based on a device modeling employing a network of interconnected microdiodes. The equivalent circuit network model takes interface and bulk resistances as well as the sheet resistance of the transparent electrode into account. The application of this model allows direct calculation of the lateral current and voltage distribution as well as determination of internal resistances and the sheet resistance of the higher resistive electrode. Furthermore, we have extended the microdiode-model to also describe and predict current voltage characteristics for devices under illumination. Finally the local nature of this description enables important conclusions concerning the geometry dependent performance of thin film solar cells.

  2. Realization of quantitative-grade fieldable snapshot imaging spectropolarimeter.

    Science.gov (United States)

    Jones, Stephen; Iannarilli, Frank; Kebabian, Paul

    2004-12-27

    We discuss achievement of a long-standing technology goal: the first practical realization of a quantitative-grade, field-worthy snapshot imaging spectropolarimeter. The instrument employs Polarimetric Spectral Intensity Modulation (PSIM), a technique that enables full Stokes instantaneous "snapshot" spectropolarimetry with perfect channel registration. This is achieved with conventional single beam optics and a single focal plane array (FPA). Simultaneity and perfect registration are obtained by encoding the polarimetry onto the spectrum via a novel optical arrangement which enables sensing from moving platforms against dynamic scenes. PSIM is feasible across the electro-optical sensing range (UV-LWIR). We present measurement results from a prototype sensor that operates in the visible and near infrared regime (450-900 nm). We discuss in some detail the calibration and Stokes spectrum inversion algorithms that are presently achieving 0.5% polarimetric accuracy.

  3. Quantitative thermo-acoustic imaging: An exact reconstruction formula

    CERN Document Server

    Ammari, Habib; Jing, Wenjia; Nguyen, Loc

    2012-01-01

    The quantitative thermo-acoustic imaging is considered in this paper. Given several data sets of electromagnetic data, we first establish an exact formula for the absorption coefficient, which involves derivatives of the given data up to the third order. However, because of the dependence of such derivatives, this formula is unstable in the sense that small measurement noises may cause large errors. Hence, with the presence of noise, the obtained formula, together with noise regularization, provides an initial guess for the true absorption coefficient. We next correct the errors by deriving a reconstruction formula based on the least square solution of an optimal control problem and show that this optimization step reduces the errors occurring.

  4. Quantitative surface evaluation by matching experimental and simulated ronchigram images

    Science.gov (United States)

    Kantún Montiel, Juana Rosaura; Cordero Dávila, Alberto; González García, Jorge

    2011-09-01

    To estimate qualitatively the surface errors with Ronchi test, the experimental and simulated ronchigrams are compared. Recently surface errors have been obtained quantitatively matching the intersection point coordinates of ronchigrama fringes with x-axis . In this case, gaussian fit must be done for each fringe, and interference orders are used in Malacara algorithm for the simulations. In order to evaluate surface errors, we added an error function in simulations, described with cubic splines, to the sagitta function of the ideal surface. We used the vectorial transversal aberration formula and a ruling with cosinusoidal transmittance, because these rulings reproduce better experimental ronchigram fringe profiles. Several error functions are tried until the whole experimental ronchigrama image is reproduced. The optimization process was done using genetic algorithms.

  5. Accuracy of quantitative reconstructions in SPECT/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shcherbinin, S; Celler, A [Department of Radiology, University of British Columbia, 366-828 West 10th Avenue, Vancouver BC, V5Z 1L8 (Canada); Belhocine, T; Vanderwerf, R; Driedger, A [Department of Nuclear Medicine, London Health Sciences Centre, 375 South Street, PO Box 5375, London ON, N6A 4G5 (Canada)], E-mail: shcher2@interchange.ubc.ca

    2008-09-07

    The goal of this study was to determine the quantitative accuracy of our OSEM-APDI reconstruction method based on SPECT/CT imaging for Tc-99m, In-111, I-123, and I-131 isotopes. Phantom studies were performed on a SPECT/low-dose multislice CT system (Infinia-Hawkeye-4 slice, GE Healthcare) using clinical acquisition protocols. Two radioactive sources were centrally and peripherally placed inside an anthropometric Thorax phantom filled with non-radioactive water. Corrections for attenuation, scatter, collimator blurring and collimator septal penetration were applied and their contribution to the overall accuracy of the reconstruction was evaluated. Reconstruction with the most comprehensive set of corrections resulted in activity estimation with error levels of 3-5% for all the isotopes.

  6. Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

    Directory of Open Access Journals (Sweden)

    Christine L. Tardif

    2012-01-01

    Full Text Available Although significant improvements have been made regarding the visualization and characterization of cortical multiple sclerosis (MS lesions using magnetic resonance imaging (MRI, cortical lesions (CL continue to be under-detected in vivo, and we have a limited understanding of the causes of GM pathology. The objective of this study was to characterize the MRI signature of CLs to help interpret the changes seen in vivo and elucidate the factors limiting their visualization. A quantitative 3D high-resolution (350 μm isotropic MRI study at 3 Tesla of a fixed post mortem cerebral hemisphere from a patient with MS is presented in combination with matched immunohistochemistry. Type III subpial lesions are characterized by an increase in T1, T2 and M0, and a decrease in MTR in comparison to the normal appearing cortex (NAC. All quantitative MR parameters were associated with cortical GM myelin content, while T1 showed the strongest correlation. The histogram analysis showed extensive overlap between CL and NAC for all MR parameters and myelin content. This is due to the poor contrast in myelin content between CL and NAC in comparison to the variability in myelo-architecture throughout the healthy cortex. This latter comparison is highlighted by the representation of T1 times on cortical surfaces at several laminar depths.

  7. Predicting phenotypic diversity and the underlying quantitative molecular transitions.

    Directory of Open Access Journals (Sweden)

    Claudiu A Giurumescu

    2009-04-01

    Full Text Available During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render approximately 500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network

  8. Molecular hydrogen polarization images of OMC-1

    Science.gov (United States)

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

    1991-01-01

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

  9. Molecular hydrogen polarization images of OMC-1

    Science.gov (United States)

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

    1991-01-01

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

  10. Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making.

    Science.gov (United States)

    Prescott, Jeffrey William

    2013-02-01

    The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

  11. Quantitative ultrasound and photoacoustic imaging for the assessment of vascular parameters

    CERN Document Server

    Meiburger, Kristen M

    2017-01-01

    This book describes the development of quantitative techniques for ultrasound and photoacoustic imaging in the assessment of architectural and vascular parameters. It presents morphological vascular research based on the development of quantitative imaging techniques for the use of clinical B-mode ultrasound images, and preclinical architectural vascular investigations on quantitative imaging techniques for ultrasounds and photoacoustics. The book is divided into two main parts, the first of which focuses on the development and validation of quantitative techniques for the assessment of vascular morphological parameters that can be extracted from B-mode ultrasound longitudinal images of the common carotid artery. In turn, the second part highlights quantitative imaging techniques for assessing the architectural parameters of vasculature that can be extracted from 3D volumes, using both contrast-enhanced ultrasound (CEUS) imaging and photoacoustic imaging without the addition of any contrast agent. Sharing and...

  12. Molecular imaging in the era of personalized medicine.

    Science.gov (United States)

    Jung, Kyung-Ho; Lee, Kyung-Han

    2015-01-01

    Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

  13. Molecular ultrasound imaging: current status and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Deshpande, N. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States); Needles, A. [Visualsonics, Toronto (Canada); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States)

    2010-07-15

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

  14. Molecular and quantitative trait variation within and among populations of the intertidal copepod Tigriopus californicus.

    Science.gov (United States)

    Edmands, Suzanne; Harrison, J Scott

    2003-10-01

    While molecular and quantitative trait variation may be theoretically correlated, empirical studies using both approaches frequently reveal discordant patterns, and these discrepancies can contribute to our understanding of evolutionary processes. Here, we assessed genetic variation in six populations of the copepod Tigriopus californicus. Molecular variation was estimated using five polymorphic microsatellite loci, and quantitative variation was measured using 22-life history and morphometric characters. Within populations, no correlation was found between the levels of molecular variation (heterozygosity) and quantitative variation (heritability). Between populations, quantitative subdivision (Q(ST)) was correlated with molecular subdivision when measured as F(ST) but not when measured as R(ST). Unlike most taxa studied to date, the overall level of molecular subdivision exceeded the level of quantitative subdivision (F(ST) = 0.80, R(ST) = 0.89, Q(ST) = 0.30). Factors that could contribute to this pattern include stabilizing or fluctuating selection on quantitative traits or accelerated rates of molecular evolution.

  15. Quantitative Image Analysis Techniques with High-Speed Schlieren Photography

    Science.gov (United States)

    Pollard, Victoria J.; Herron, Andrew J.

    2017-01-01

    Optical flow visualization techniques such as schlieren and shadowgraph photography are essential to understanding fluid flow when interpreting acquired wind tunnel test data. Output of the standard implementations of these visualization techniques in test facilities are often limited only to qualitative interpretation of the resulting images. Although various quantitative optical techniques have been developed, these techniques often require special equipment or are focused on obtaining very precise and accurate data about the visualized flow. These systems are not practical in small, production wind tunnel test facilities. However, high-speed photography capability has become a common upgrade to many test facilities in order to better capture images of unsteady flow phenomena such as oscillating shocks and flow separation. This paper describes novel techniques utilized by the authors to analyze captured high-speed schlieren and shadowgraph imagery from wind tunnel testing for quantification of observed unsteady flow frequency content. Such techniques have applications in parametric geometry studies and in small facilities where more specialized equipment may not be available.

  16. Quantitative assessment of hip osteoarthritis based on image texture analysis.

    Science.gov (United States)

    Boniatis, I S; Costaridou, L I; Cavouras, D A; Panagiotopoulos, E C; Panayiotakis, G S

    2006-03-01

    A non-invasive method was developed to investigate the potential capacity of digital image texture analysis in evaluating the severity of hip osteoarthritis (OA) and in monitoring its progression. 19 textural features evaluating patterns of pixel intensity fluctuations were extracted from 64 images of radiographic hip joint spaces (HJS), corresponding to 32 patients with verified unilateral or bilateral OA. Images were enhanced employing custom developed software for the delineation of the articular margins on digitized pelvic radiographs. The severity of OA for each patient was assessed by expert orthopaedists employing the Kellgren and Lawrence (KL) scale. Additionally, an index expressing HJS-narrowing was computed considering patients from the unilateral OA-group. A textural feature that quantified pixel distribution non-uniformity (grey level non-uniformity, GLNU) demonstrated the strongest correlation with the HJS-narrowing index among all extracted features and utilized in further analysis. Classification rules employing GLNU feature were introduced to characterize a hip as normal or osteoarthritic and to assign it to one of three severity categories, formed in accordance with the KL scale. Application of the proposed rules resulted in relatively high classification accuracies in characterizing a hip as normal or osteoarthritic (90.6%) and in assigning it to the correct KL scale category (88.9%). Furthermore, the strong correlation between the HJS-narrowing index and the pathological GLNU (r = -0.9, p<0.001) was utilized to provide percentages quantifying hip OA-severity. Texture analysis may contribute in the quantitative assessment of OA-severity, in the monitoring of OA-progression and in the evaluation of a chondroprotective therapy.

  17. Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

    Science.gov (United States)

    D'Arienzo, M; Cazzato, M; Cozzella, M L; Cox, M; D'Andrea, M; Fazio, A; Fenwick, A; Iaccarino, G; Johansson, L; Strigari, L; Ungania, S; De Felice, P

    2016-06-01

    Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in

  18. Molecular diagnosis of sex chromosome aneuploidy using quantitative PCR.

    Science.gov (United States)

    Mutter, G L; Pomponio, R J

    1991-08-11

    Numeric sex chromosome imbalances, or aneuploidies, are present in several pathological conditions including tumors, abnormal gestations, and clinical syndromes. Here we report a method to identify karyotypic imbalances of the X and Y chromosomes using the polymerase chain reaction (PCR). The polymerase chain reaction was used to quantitatively coamplify the sex chromosome linked genes ZFX and ZFY. Quantitation was facilitated by 1) use of a single primer set which recognizes both templates, 2) incorporation of radiolabelled nucleotides during amplification, and 3) use of amplification conditions which minimize heteroduplex formation. High accuracy of the method was confirmed by concordance with values expected from titrated male and female DNAs and cells from patients with sex chromosome aneuploidy. This approach provides a rapid and reproducible method of evaluating relative abundance of allelic genes, and might be applied to detection of autosomal aneuploidy.

  19. Phenol-formaldehyde resins: A quantitative NMR study of molecular structure and molecular dynamics

    Science.gov (United States)

    Ottenbourgs, Benjamin Tony

    Phenol-formaldehyde (PF) resins have been the subject of this work. 13C liquid-state and solid-state NMR has been used to investigate the molecular structure of mainly novolak and partially of resole resins. 1H wideline in combination with 13C solid-state NMR relaxometry has been applied to study the curing and the molecular dynamics of phenolic resins. It was the intention to provide an insight in the relationship between resin composition, resin structure and subsequent resin properties (by means of the molecular dynamics). An improved 13C liquid-state NMR quantification technique of novolaks in THF-CDCl3 solutions is demonstrated. Full quantitative 13C liquid-state spectra of phenol-formaldehyde resins with high signal- to-noise ratio were obtained by using chromium acetylacetonate under optimized spectral conditions within a few hours spectrometer time. Attached proton test (APT) spectra enabled proper peak assignments in the region with significant overlap. For several novolaks, prepared under different catalytic conditions, the degree of polymerization, degree of branching, number average molecular weight, isomeric distribution, and the number of unreacted ortho and para phenol ring positions was determined with a reduced margin of error, by analyzing and integrating the 13C spectra. The power of 13C solid-state NMR in the analysis of cured PF resins is shown. Particular importance was ascribed to the question of the quantifiability of the experiments when it was desired to measure the degree of conversion by means of a 13C CP/MAS contact time study. The network structure present, and thus also the mechanical properties, is critically dependent upon the final degree of conversion obtained after curing. The degree of conversion, which depended on the cure conditions (cure temperature, cure pressure and cure time), was limited by vitrification as was demonstrated by DSC experiments. Changes in the spin-lattice relaxation time T 1H were observed, providing

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

    Science.gov (United States)

    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.

  1. Quantitative image reconstruction for total-body PET imaging using the 2-meter long EXPLORER scanner.

    Science.gov (United States)

    Zhang, Xuezhu; Zhou, Jian; Cherry, Simon R; Badawi, Ramsey D; Qi, Jinyi

    2017-03-21

    The EXPLORER project aims to build a 2 meter long total-body PET scanner, which will provide extremely high sensitivity for imaging the entire human body. It will possess a range of capabilities currently unavailable to state-of-the-art clinical PET scanners with a limited axial field-of-view. The huge number of lines-of-response (LORs) of the EXPLORER poses a challenge to the data handling and image reconstruction. The objective of this study is to develop a quantitative image reconstruction method for the EXPLORER and compare its performance with current whole-body scanners. Fully 3D image reconstruction was performed using time-of-flight list-mode data with parallel computation. To recover the resolution loss caused by the parallax error between crystal pairs at a large axial ring difference or transaxial radial offset, we applied an image domain resolution model estimated from point source data. To evaluate the image quality, we conducted computer simulations using the SimSET Monte-Carlo toolkit and XCAT 2.0 anthropomorphic phantom to mimic a 20 min whole-body PET scan with an injection of 25 MBq (18)F-FDG. We compare the performance of the EXPLORER with a current clinical scanner that has an axial FOV of 22 cm. The comparison results demonstrated superior image quality from the EXPLORER with a 6.9-fold reduction in noise standard deviation comparing with multi-bed imaging using the clinical scanner.

  2. Characterization of sweet cassava accessions based on molecular, quantitative and qualitative data

    Directory of Open Access Journals (Sweden)

    Eduardo Alano Vieira

    2011-01-01

    Full Text Available The purpose of this study was to estimate the genetic divergence in sweet cassava accessions by molecular markersand quantitative and qualitative characters, as well as determine the correlation between these estimates. Sixteen sweet cassavaaccessions of the Regional Cassava Germplasm Bank of the Cerrado were evaluated under field conditions, for 13 quantitative and33 qualitative characters. In the laboratory, the accessions were evaluated with RAPD markers. Subsequently, matrixes of geneticdissimilarity/distance among the accessions were estimated based on molecular markers and quantitative and qualitative characters.Besides, the significance of the correlation between the matrixes was estimated. The RAPD, qualitative and quantitative dataindicated the existence of high divergence among the accessions. The divergences estimated by molecular markers and by quantitativetraits were weakly associated with each other and moderately with the divergence estimated by qualitative characters.

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

    Science.gov (United States)

    Wang, Ping; Moore, Anna

    2012-01-01

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

  4. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Volkan Beylergil

    2014-04-01

    Full Text Available Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC, a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

  5. Click reaction: An applicable radiolabeling method for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ji Young; Lee, Byung Chul [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of)

    2015-12-15

    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.

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

    Science.gov (United States)

    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.

  7. Molecular Imaging and Precision Medicine in Prostate Cancer.

    Science.gov (United States)

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

    2017-01-01

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

  8. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization

    National Research Council Canada - National Science Library

    Elschot, Mattijs; Nijsen, Johannes Franciscus Wilhelmus; Dam, Alida Johanna; de Jong, Hugo Wilhelmus Antonius Maria

    2011-01-01

    .... The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared...

  9. Thermography as a quantitative imaging method for assessing postoperative inflammation

    Science.gov (United States)

    Christensen, J; Matzen, LH; Vaeth, M; Schou, S; Wenzel, A

    2012-01-01

    Objective To assess differences in skin temperature between the operated and control side of the face after mandibular third molar surgery using thermography. Methods 127 patients had 1 mandibular third molar removed. Before the surgery, standardized thermograms were taken of both sides of the patient's face using a Flir ThermaCam™ E320 (Precisions Teknik AB, Halmstad, Sweden). The imaging procedure was repeated 2 days and 7 days after surgery. A region of interest including the third molar region was marked on each image. The mean temperature within each region of interest was calculated. The difference between sides and over time were assessed using paired t-tests. Results No significant difference was found between the operated side and the control side either before or 7 days after surgery (p > 0.3). The temperature of the operated side (mean: 32.39 °C, range: 28.9–35.3 °C) was higher than that of the control side (mean: 32.06 °C, range: 28.5–35.0 °C) 2 days after surgery [0.33 °C, 95% confidence interval (CI): 0.22–0.44 °C, p 0.1). After 2 days, the operated side was not significantly different from the temperature pre-operatively (p = 0.12), whereas the control side had a lower temperature (0.57 °C, 95% CI: 0.29–0.86 °C, p < 0.001). Conclusions Thermography seems useful for quantitative assessment of inflammation between the intervention side and the control side after surgical removal of mandibular third molars. However, thermography cannot be used to assess absolute temperature changes due to normal variations in skin temperature over time. PMID:22752326

  10. Mapping Quantitative Trait Loci Controlling Endosperm Traits with Molecular Marker

    Institute of Scientific and Technical Information of China (English)

    XU Chen-wu; LI Tao; SUN Chang-sen; GU Shi-liang

    2002-01-01

    Based on the genetic models for triploid endosperm traits and on the methods for mapping diploid quantitative traits loci (QTLs), the genetic constitutions, components of means and genetic variances of QTL controlling endosperm traits under flanking marker genotypes of different generations were presented. From these results, a multiple linear regression method for mapping QTL underlying endosperm traits in cereals was proposed, which used the means of endosperm traits under flanking marker genotypes as a dependent variable, the coefficient of additive effect ( d ) and dominance effect ( h 1 and/or h2 ) of a putative QTL in a given interval as independent variables. This method can work at any position in a genome covered by markers and increase the estimation precision of QTL location and their effects by eliminating the interference of other relative QTLs. This method can also be easily used in other uneven data such as markers and quantitative traits detected or measured in plants and tissues different either in generations or at chromosomal ploidy levels, and in endosperm traits controlled by complicated genetic models considering the effects produced by genotypes of both maternal plants and seeds on them.

  11. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2009-03-01

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

  12. Molecular imaging in Libman-Sacks endocarditis.

    Science.gov (United States)

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

    2015-04-01

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

  13. Quantitative image analysis of HIV-1 infection in lymphoid tissue

    Energy Technology Data Exchange (ETDEWEB)

    Haase, A.T.; Zupancic, M.; Cavert, W. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)] [and others

    1996-11-08

    Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy. A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productivity infected cells. Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment. 22 refs., 2 figs., 2 tabs.

  14. Scatter rejection in quantitative thermal and cold neutron imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tremsin, A.S., E-mail: ast@ssl.berkeley.edu [Space Sciences Laboratory, University of California at Berkeley, Berkeley, CA 94720 (United States); Kardjilov, N; Dawson, M; Strobl, M.; Manke, I. [Helmholtz-Zentrum Berlin, 14109 Berlin (Germany); McPhate, J.B.; Vallerga, J.V.; Siegmund, O.H.W. [Space Sciences Laboratory, University of California at Berkeley, Berkeley, CA 94720 (United States); Feller, W.B. [Nova Scientific, Inc., 10 Picker Road, Sturbridge, MA 01566 (United States)

    2011-09-21

    The accuracy of quantitative neutron transmission radiography can be substantially decreased if highly scattering materials, such as water or plastics, exist in the sample. There are currently two main solutions to this problem: either performing experiments at a large distance between the detector and the sample or employ some numerical correction techniques. In the former case, the spatial resolution is substantially reduced by the limited beam divergence, while the latter correction requires a priori information about the sample and is limited to distances of above {approx}2 cm. We demonstrate the feasibility of another technique, namely the possibility to remove the scattered neutron component from the transmitted neutron beam by a very compact polycapillary collimator. These {approx}1 mm thick devices can be placed between the sample and the detector and remove most of the neutrons scattered at angles larger than the acceptance angle of the collimator (typically 1{sup o}). No image distortions above {approx}10 {mu}m scales are introduced by these collimators. The neutron transmission of highly scattering samples (water and plexiglass) is measured in our experiments with and without scatter rejection. In the latter case, the accuracy of measured transmission coefficient was substantially improved by our collimators.

  15. Quantitating subcellular metabolism with multi-isotope imaging mass spectrometry

    Science.gov (United States)

    Steinhauser, Matthew L.; Bailey, Andrew; Senyo, Samuel E.; Guillermier, Christelle; Perlstein, Todd S.; Gould, Alex P.; Lee, Richard T.; Lechene, Claude P.

    2011-01-01

    Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter1,2 but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with sub-micron resolution3,4. Here we apply MIMS to diverse organisms, including Drosophila, mice, and humans. We test the “immortal strand hypothesis,” which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labeling mice with 15N-thymidine from gestation through post-natal week 8, we find no 15N label retention by dividing small intestinal crypt cells after 4wk chase. In adult mice administered 15N-thymidine pulse-chase, we find that proliferating crypt cells dilute label consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human hematopoietic system. These studies show that MIMS provides high-resolution quantitation of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research. PMID:22246326

  16. Ultrasound for molecular imaging and therapy in cancer

    OpenAIRE

    Kaneko, Osamu F; Willmann, Jürgen K.

    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 th...

  17. Computational methods in molecular imaging technologies

    CERN Document Server

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

    2017-01-01

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

  18. Resonance Energy Transfer Molecular Imaging Application in Biomedicine

    Directory of Open Access Journals (Sweden)

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

    2016-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-15

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

  20. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I

    DEFF Research Database (Denmark)

    Willis, Tracey A; Hollingsworth, Kieren G; Coombs, Anna

    2014-01-01

    -related protein (FKRP) gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by qualitative grading for 15 individual lower limb muscles and quantitative Dixon imaging was analysed on 14 individual lower limb muscles by region of interest analysis. We described the pattern and appearance......) that the quantitative Dixon technique is an objective quantitative marker of disease and (ii) new observations of gender specific patterns of muscle involvement in LGMD2I....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-05-15

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

  2. Time-resolved quantitative multiphase interferometric imaging of a highly focused ultrasound pulse

    CERN Document Server

    Souris, Fabien; Jacquier, Philippe; Dupont-Roc, Jacques; Arvengas, Arnaud; Caupin, Frédéric; 10.1364/AO.49.006127

    2010-01-01

    Interferometric imaging is a well established method to image phase objects by mixing the image wavefront with a reference one on a CCD camera. It has also been applied to fast transient phenomena, mostly through the analysis of single interferograms. It is shown that for repetitive phenomena multiphase acquisition brings significant advantages. A 1 MHz focused sound field emitted by a hemispherical piezotransducer in water is imaged as an example. Quantitative image analysis provides high resolution sound field profiles. Pressure at focus determined by this method agrees with measurements from a fiber-optic probe hydrophone. This confirms that multiphase interferometric imaging can indeed provide quantitative measurements.

  3. Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states.

    Science.gov (United States)

    Ehmann, Nadine; van de Linde, Sebastian; Alon, Amit; Ljaschenko, Dmitrij; Keung, Xi Zhen; Holm, Thorge; Rings, Annika; DiAntonio, Aaron; Hallermann, Stefan; Ashery, Uri; Heckmann, Manfred; Sauer, Markus; Kittel, Robert J

    2014-08-18

    The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by the diffraction-limited resolution of conventional light microscopy. Here we introduce new approaches to quantify endogenous protein organization at single-molecule resolution in situ with super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of which are organized into about 15 heptameric clusters. We test for a quantitative relationship between CAZ ultrastructure and neurotransmitter release properties by engaging Drosophila mutants and electrophysiology. Our results indicate that the precise nanoscopic organization of Brp distinguishes different physiological AZ states and link functional diversification to a heretofore unrecognized neuronal gradient of the CAZ ultrastructure.

  4. Prospects and challenges of quantitative phase imaging in tumor cell biology

    Science.gov (United States)

    Kemper, Björn; Götte, Martin; Greve, Burkhard; Ketelhut, Steffi

    2016-03-01

    Quantitative phase imaging (QPI) techniques provide high resolution label-free quantitative live cell imaging. Here, prospects and challenges of QPI in tumor cell biology are presented, using the example of digital holographic microscopy (DHM). It is shown that the evaluation of quantitative DHM phase images allows the retrieval of different parameter sets for quantification of cellular motion changes in migration and motility assays that are caused by genetic modifications. Furthermore, we demonstrate simultaneously label-free imaging of cell growth and morphology properties.

  5. Graphics processing unit-based quantitative second-harmonic generation imaging.

    Science.gov (United States)

    Kabir, Mohammad Mahfuzul; Jonayat, A S M; Patel, Sanjay; Toussaint, Kimani C

    2014-09-01

    We adapt a graphics processing unit (GPU) to dynamic quantitative second-harmonic generation imaging. We demonstrate the temporal advantage of the GPU-based approach by computing the number of frames analyzed per second from SHG image videos showing varying fiber orientations. In comparison to our previously reported CPU-based approach, our GPU-based image analysis results in ∼10× improvement in computational time. This work can be adapted to other quantitative, nonlinear imaging techniques and provides a significant step toward obtaining quantitative information from fast in vivo biological processes.

  6. Quantitative analysis of genomic element interactions by molecular colony technique.

    Science.gov (United States)

    Gavrilov, Alexey A; Chetverina, Helena V; Chermnykh, Elina S; Razin, Sergey V; Chetverin, Alexander B

    2014-03-01

    Distant genomic elements were found to interact within the folded eukaryotic genome. However, the used experimental approach (chromosome conformation capture, 3C) enables neither determination of the percentage of cells in which the interactions occur nor demonstration of simultaneous interaction of >2 genomic elements. Each of the above can be done using in-gel replication of interacting DNA segments, the technique reported here. Chromatin fragments released from formaldehyde-cross-linked cells by sodium dodecyl sulfate extraction and sonication are distributed in a polyacrylamide gel layer followed by amplification of selected test regions directly in the gel by multiplex polymerase chain reaction. The fragments that have been cross-linked and separate fragments give rise to multi- and monocomponent molecular colonies, respectively, which can be distinguished and counted. Using in-gel replication of interacting DNA segments, we demonstrate that in the material from mouse erythroid cells, the majority of fragments containing the promoters of active β-globin genes and their remote enhancers do not form complexes stable enough to survive sodium dodecyl sulfate extraction and sonication. This indicates that either these elements do not interact directly in the majority of cells at a given time moment, or the formed DNA-protein complex cannot be stabilized by formaldehyde cross-linking.

  7. Assessing the Accuracy of Quantitative Molecular Microbial Profiling

    Directory of Open Access Journals (Sweden)

    Denise M. O'Sullivan

    2014-11-01

    Full Text Available The application of high-throughput sequencing in profiling microbial communities is providing an unprecedented ability to investigate microbiomes. Such studies typically apply one of two methods: amplicon sequencing using PCR to target a conserved orthologous sequence (typically the 16S ribosomal RNA gene or whole (metagenome sequencing (WGS. Both methods have been used to catalog the microbial taxa present in a sample and quantify their respective abundances. However, a comparison of the inherent precision or bias of the different sequencing approaches has not been performed. We previously developed a metagenomic control material (MCM to investigate error when performing different sequencing strategies. Amplicon sequencing using four different primer strategies and two 16S rRNA regions was examined (Roche 454 Junior and compared to WGS (Illumina HiSeq. All sequencing methods generally performed comparably and in good agreement with organism specific digital PCR (dPCR; WGS notably demonstrated very high precision. Where discrepancies between relative abundances occurred they tended to differ by less than twofold. Our findings suggest that when alternative sequencing approaches are used for microbial molecular profiling they can perform with good reproducibility, but care should be taken when comparing small differences between distinct methods. This work provides a foundation for future work comparing relative differences between samples and the impact of extraction methods. We also highlight the value of control materials when conducting microbial profiling studies to benchmark methods and set appropriate thresholds.

  8. Molecular Imaging and Therapy of Prostate Cancer

    Science.gov (United States)

    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.

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

    CERN Document Server

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

    2016-01-01

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

  10. Molecular imaging of angiogenesis with SPECT.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Boerman, O.C.

    2010-01-01

    Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life th

  11. The emerging science of quantitative imaging biomarkers terminology and definitions for scientific studies and regulatory submissions.

    Science.gov (United States)

    Kessler, Larry G; Barnhart, Huiman X; Buckler, Andrew J; Choudhury, Kingshuk Roy; Kondratovich, Marina V; Toledano, Alicia; Guimaraes, Alexander R; Filice, Ross; Zhang, Zheng; Sullivan, Daniel C

    2015-02-01

    The development and implementation of quantitative imaging biomarkers has been hampered by the inconsistent and often incorrect use of terminology related to these markers. Sponsored by the Radiological Society of North America, an interdisciplinary group of radiologists, statisticians, physicists, and other researchers worked to develop a comprehensive terminology to serve as a foundation for quantitative imaging biomarker claims. Where possible, this working group adapted existing definitions derived from national or international standards bodies rather than invent new definitions for these terms. This terminology also serves as a foundation for the design of studies that evaluate the technical performance of quantitative imaging biomarkers and for studies of algorithms that generate the quantitative imaging biomarkers from clinical scans. This paper provides examples of research studies and quantitative imaging biomarker claims that use terminology consistent with these definitions as well as examples of the rampant confusion in this emerging field. We provide recommendations for appropriate use of quantitative imaging biomarker terminological concepts. It is hoped that this document will assist researchers and regulatory reviewers who examine quantitative imaging biomarkers and will also inform regulatory guidance. More consistent and correct use of terminology could advance regulatory science, improve clinical research, and provide better care for patients who undergo imaging studies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Quantitative imaging of selenoprotein with multi-isotope imaging mass spectrometry (MIMS).

    Science.gov (United States)

    Tang, Shiow-Shih; Guillermier, Christelle; Wang, Mei; Poczatek, Joseph Collin; Suzuki, Noriyuki; Loscalzo, Joseph; Lechene, Claude

    2014-11-01

    Multi-isotope imaging mass spectrometry (MIMS) allows high resolution quantitative imaging of protein and nucleic acid synthesis at the level of a single cell using stable isotope labels. We employed MIMS to determine the compartmental localization of selenoproteins tagged with stable isotope selenium compounds in human aortic endothelial cells (HAEC), and to compare the efficiency of labeling (to determine the ideal selenium source) from these compounds: [(82)Se]-selenite, [(77)Se]-seleno-methionine, and [(76)Se]-methyl-selenocysteine. We found that all three selenium sources appear to be localized in the nucleus as well as in the cytoplasm in HAEC. Seleno-methionine appears to be a better source for (seleno)protein synthesis. For MIMS detection, we compared freeze-drying to thin layer vs. thin sectioning for sample preparation. MIMS provides a unique and novel way to dissect selenoprotein synthesis in cells.

  13. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    Science.gov (United States)

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  14. Quantitative measurement of holographic image quality using Adobe Photoshop

    Science.gov (United States)

    Wesly, E.

    2013-02-01

    Measurement of the characteristics of image holograms in regards to diffraction efficiency and signal to noise ratio are demonstrated, using readily available digital cameras and image editing software. Illustrations and case studies, using currently available holographic recording materials, are presented.

  15. Quantitative approach on SEM images of microstructure of clay soils

    Institute of Scientific and Technical Information of China (English)

    施斌; 李生林; M.Tolkachev

    1995-01-01

    The working principles of Videolab Image Processing System (VIPS), the examining methods of orientation of microstructural units of clay soils and analysing results on SEM images of some typical microstructures of clay soils using the VIPS are introduced.

  16. Multimodality molecular imaging of stem cells therapy for stroke.

    Science.gov (United States)

    Chao, Fangfang; Shen, Yehua; 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.

  17. Agents described in the Molecular Imaging and Contrast Agent Database for imaging carbonic anhydrase IX expression.

    Science.gov (United States)

    Sneddon, Deborah; Poulsen, Sally-Ann

    2014-10-01

    Carbonic anhydrase IX (CA IX) is selectively expressed in a range of hypoxic tumours and is a validated endogenous hypoxia marker with prognostic significance; hence, CA IX is of great interest as a molecular imaging target in oncology. In this review, we present an overview of the different imaging agents and imaging modalities that have been applied for the in vivo detection of CA IX. The imaging agents reviewed are all entries in the Molecular Imaging and Contrast Agent Database (MICAD) and comprise antibody, antibody fragments and small molecule imaging agents. The effectiveness of these agents for imaging CA IX in vivo gave variable performance; however, a number of agents proved very capable. As molecular imaging has become indispensable in current medical practice we anticipate that the clinical significance of CA IX will see continued development and improvements in imaging agents for targeting this enzyme.

  18. Automatic quantitative analysis of cardiac MR perfusion images

    NARCIS (Netherlands)

    Breeuwer, Marcel; Spreeuwers, Luuk; Quist, Marcel

    2001-01-01

    Magnetic Resonance Imaging (MRI) is a powerful technique for imaging cardiovascular diseases. The introduction of cardiovascular MRI into clinical practice is however hampered by the lack of efficient and accurate image analysis methods. This paper focuses on the evaluation of blood perfusion in the

  19. Quantitative imaging through a spectrograph. 1. Principles and theory.

    NARCIS (Netherlands)

    Tolboom, R.A.L.; Dam, N.J.; Meulen, J.J. ter; Mooij, J.M.; Maassen, J.D.M.

    2004-01-01

    Laser-based optical diagnostics, such as planar laser-induced fluorescence and, especially, Raman imaging, often require selective spectral filtering. We advocate the use of an imaging spectrograph with a broad entrance slit as a spectral filter for two-dimensional imaging. A spectrograph in this mo

  20. Quantitative imaging through a spectrograph. 1. Principles and theory.

    NARCIS (Netherlands)

    Tolboom, R.A.L.; Dam, N.J.; Meulen, J.J. ter; Mooij, J.M.; Maassen, J.D.M.

    2004-01-01

    Laser-based optical diagnostics, such as planar laser-induced fluorescence and, especially, Raman imaging, often require selective spectral filtering. We advocate the use of an imaging spectrograph with a broad entrance slit as a spectral filter for two-dimensional imaging. A spectrograph in this mo

  1. Childhood white matter disorders : quantitative MR imaging and spectroscopy

    NARCIS (Netherlands)

    van der Voorn, J Patrick; Pouwels, Petra J W; Hart, Augustinus A M; Serrarens, Judith; Willemsen, Michèl A A P; Kremer, Hubertus P H; Barkhof, Frederik; van der Knaap, Marjo S

    2006-01-01

    PURPOSE: To prospectively investigate whether quantitative magnetic resonance (MR) parameters, including magnetization transfer ratio (MTR), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and MR spectroscopic metabolite concentrations, allow for discrimination between different ty

  2. Childhood white matter disorders: quantitative MR imaging and spectroscopy.

    NARCIS (Netherlands)

    Voorn, J.P. van der; Pouwels, P.J.; Hart, A.A.M.; Serrarens, J.; Willemsen, M.A.A.P.; Kremer, H.P.H.; Barkhof, F.; Knaap, M.S. van der

    2006-01-01

    PURPOSE: To prospectively investigate whether quantitative magnetic resonance (MR) parameters, including magnetization transfer ratio (MTR), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and MR spectroscopic metabolite concentrations, allow for discrimination between different ty

  3. Quantitative imaging of a non-combusting diesel spray using structured laser illumination planar imaging

    Science.gov (United States)

    Berrocal, E.; Kristensson, E.; Hottenbach, P.; Aldén, M.; Grünefeld, G.

    2012-12-01

    Due to its transient nature, high atomization process, and rapid generation of fine evaporating droplets, diesel sprays have been, and still remain, one of the most challenging sprays to be fully analyzed and understood by means of non-intrusive diagnostics. The main limitation of laser techniques for quantitative measurements of diesel sprays concerns the detection of the multiple light scattering resulting from the high optical density of such a scattering medium. A second limitation is the extinction of the incident laser radiation as it crosses the spray, as well as the attenuation of the signal which is to be detected. All these issues have strongly motivated, during the past decade, the use of X-ray instead of visible light for dense spray diagnostics. However, we demonstrate in this paper that based on an affordable Nd:YAG laser system, structured laser illumination planar imaging (SLIPI) can provide accurate quantitative description of a non-reacting diesel spray injected at 1,100 bar within a room temperature vessel pressurized at 18.6 bar. The technique is used at λ = 355 nm excitation wavelength with 1.0 mol% TMPD dye concentration, for simultaneous LIF/Mie imaging. Furthermore, a novel dual-SLIPI configuration is tested with Mie scattering detection only. The results confirm that a mapping of both the droplet Sauter mean diameter and extinction coefficient can be obtained by such complementary approaches. These new insights are provided in this article at late times after injection start. It is demonstrated that the application of SLIPI to diesel sprays provides valuable quantitative information which was not previously accessible.

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

    Science.gov (United States)

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

    2016-07-01

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

  5. Molecular aspects of magnetic resonance imaging and spectroscopy.

    Science.gov (United States)

    Boesch, C

    1999-01-01

    Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

  6. Quantitative PET imaging with the 3T MR-BrainPET

    Energy Technology Data Exchange (ETDEWEB)

    Weirich, C., E-mail: c.weirich@fz-juelich.de [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Scheins, J.; Lohmann, P.; Tellmann, L. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Byars, L.; Michel, C. [Siemens Healthcare, Molecular Imaging, Knoxville, TN (United States); Rota Kops, E.; Brenner, D.; Herzog, H.; Shah, N.J. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany)

    2013-02-21

    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner.

  7. Quantitative Genetics in the Era of Molecular Genetics: Learning Abilities and Disabilities as an Example

    Science.gov (United States)

    Haworth, Claire M. A.; Plomin, Robert

    2010-01-01

    Objective: To consider recent findings from quantitative genetic research in the context of molecular genetic research, especially genome-wide association studies. We focus on findings that go beyond merely estimating heritability. We use learning abilities and disabilities as examples. Method: Recent twin research in the area of learning…

  8. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of /ital Homo sapiens/

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This volume is the second part of a collection of papers submitted by the participants to the 1986 Cold Spring Harbor Symposium on Quantitative Biology entitled Molecular Biology of /ital Homo sapiens/. The 49 papers included in this volume are grouped by subject into receptors, human cancer genes, and gene therapy. (DT)

  9. Molecular imaging of HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

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

  10. Advances of molecular imaging in epilepsy

    OpenAIRE

    Galovic, M.; Koepp, M.

    2016-01-01

    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 loc...

  11. Advances of Molecular Imaging in Epilepsy

    OpenAIRE

    Galovic, Marian; Koepp, Matthias

    2016-01-01

    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 loc...

  12. Segmentation and learning in the quantitative analysis of microscopy images

    Science.gov (United States)

    Ruggiero, Christy; Ross, Amy; Porter, Reid

    2015-02-01

    In material science and bio-medical domains the quantity and quality of microscopy images is rapidly increasing and there is a great need to automatically detect, delineate and quantify particles, grains, cells, neurons and other functional "objects" within these images. These are challenging problems for image processing because of the variability in object appearance that inevitably arises in real world image acquisition and analysis. One of the most promising (and practical) ways to address these challenges is interactive image segmentation. These algorithms are designed to incorporate input from a human operator to tailor the segmentation method to the image at hand. Interactive image segmentation is now a key tool in a wide range of applications in microscopy and elsewhere. Historically, interactive image segmentation algorithms have tailored segmentation on an image-by-image basis, and information derived from operator input is not transferred between images. But recently there has been increasing interest to use machine learning in segmentation to provide interactive tools that accumulate and learn from the operator input over longer periods of time. These new learning algorithms reduce the need for operator input over time, and can potentially provide a more dynamic balance between customization and automation for different applications. This paper reviews the state of the art in this area, provides a unified view of these algorithms, and compares the segmentation performance of various design choices.

  13. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

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

  14. Cerenkov imaging - a new modality for molecular imaging

    OpenAIRE

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

    2012-01-01

    Cerenkov luminescence imaging (CLI) is an emerging hybrid modality that utilizes the light emission from many commonly used medical isotopes. Cerenkov radiation (CR) is produced when charged particles travel through a dielectric medium faster than the speed of light in that medium. First described in detail nearly 100 years ago, CR has only recently applied for biomedical imaging purposes. The modality is of considerable interest as it enables the use of widespread luminescence imaging equipm...

  15. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    Science.gov (United States)

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

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

    Science.gov (United States)

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

    2007-06-01

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

  17. Optical Molecular Imaging of Ultrasound-mediated Drug Delivery

    NARCIS (Netherlands)

    Derieppe, M.P.P.

    2015-01-01

    The goal of this PhD project was to develop optical molecular imaging methods to study drug delivery facilitated by ultrasound waves (US) and hyperthermia. Fibered confocal fluorescence microscopy (FCFM), together with dedicated image analysis, was used in vitro on a cell monolayer, and in vivo at

  18. Mammographic quantitative image analysis and biologic image composition for breast lesion characterization and classification

    Energy Technology Data Exchange (ETDEWEB)

    Drukker, Karen, E-mail: kdrukker@uchicago.edu; Giger, Maryellen L.; Li, Hui [Department of Radiology, University of Chicago, Chicago, Illinois 60637 (United States); Duewer, Fred; Malkov, Serghei; Joe, Bonnie; Kerlikowske, Karla; Shepherd, John A. [Radiology Department, University of California, San Francisco, California 94143 (United States); Flowers, Chris I. [Department of Radiology, University of South Florida, Tampa, Florida 33612 (United States); Drukteinis, Jennifer S. [Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 (United States)

    2014-03-15

    Purpose: To investigate whether biologic image composition of mammographic lesions can improve upon existing mammographic quantitative image analysis (QIA) in estimating the probability of malignancy. Methods: The study population consisted of 45 breast lesions imaged with dual-energy mammography prior to breast biopsy with final diagnosis resulting in 10 invasive ductal carcinomas, 5 ductal carcinomain situ, 11 fibroadenomas, and 19 other benign diagnoses. Analysis was threefold: (1) The raw low-energy mammographic images were analyzed with an established in-house QIA method, “QIA alone,” (2) the three-compartment breast (3CB) composition measure—derived from the dual-energy mammography—of water, lipid, and protein thickness were assessed, “3CB alone”, and (3) information from QIA and 3CB was combined, “QIA + 3CB.” Analysis was initiated from radiologist-indicated lesion centers and was otherwise fully automated. Steps of the QIA and 3CB methods were lesion segmentation, characterization, and subsequent classification for malignancy in leave-one-case-out cross-validation. Performance assessment included box plots, Bland–Altman plots, and Receiver Operating Characteristic (ROC) analysis. Results: The area under the ROC curve (AUC) for distinguishing between benign and malignant lesions (invasive and DCIS) was 0.81 (standard error 0.07) for the “QIA alone” method, 0.72 (0.07) for “3CB alone” method, and 0.86 (0.04) for “QIA+3CB” combined. The difference in AUC was 0.043 between “QIA + 3CB” and “QIA alone” but failed to reach statistical significance (95% confidence interval [–0.17 to + 0.26]). Conclusions: In this pilot study analyzing the new 3CB imaging modality, knowledge of the composition of breast lesions and their periphery appeared additive in combination with existing mammographic QIA methods for the distinction between different benign and malignant lesion types.

  19. Quantitative Determination of Organic Semiconductor Microstructure from the Molecular to Device Scale

    KAUST Repository

    Rivnay, Jonathan

    2012-10-10

    A study was conducted to demonstrate quantitative determination of organic semiconductor microstructure from the molecular to device scale. The quantitative determination of organic semiconductor microstructure from the molecular to device scale was key to obtaining precise description of the molecular structure and microstructure of the materials of interest. This information combined with electrical characterization and modeling allowed for the establishment of general design rules to guide future rational design of materials and devices. Investigations revealed that a number and variety of defects were the largest contributors to the existence of disorder within a lattice, as organic semiconductor crystals were dominated by weak van der Waals bonding. Crystallite size, texture, and variations in structure due to spatial confinement and interfaces were also found to be relevant for transport of free charge carriers and bound excitonic species over distances that were important for device operation.

  20. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

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

  1. Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

    Science.gov (United States)

    Mallik, Atul K; Drzezga, Alexander; Minoshima, Satoshi

    2017-01-01

    Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

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

    2013-01-01

    Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers...... for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections...... With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas....

  3. Wide-field quantitative imaging of tissue microstructure using sub-diffuse spatial frequency domain imaging.

    Science.gov (United States)

    McClatchy, David M; Rizzo, Elizabeth J; Wells, Wendy A; Cheney, Philip P; Hwang, Jeeseong C; Paulsen, Keith D; Pogue, Brian W; Kanick, Stephen C

    2016-06-20

    Localized measurements of scattering in biological tissue provide sensitivity to microstructural morphology but have limited utility to wide-field applications, such as surgical guidance. This study introduces sub-diffusive spatial frequency domain imaging (sd-SFDI), which uses high spatial frequency illumination to achieve wide-field sampling of localized reflectances. Model-based inversion recovers macroscopic variations in the reduced scattering coefficient [Formula: see text] and the phase function backscatter parameter (γ). Measurements in optical phantoms show quantitative imaging of user-tuned phase-function-based contrast with accurate decoupling of parameters that define both the density and the size-scale distribution of scatterers. Measurements of fresh ex vivo breast tissue samples revealed, for the first time, unique clustering of sub-diffusive scattering properties for different tissue types. The results support that sd-SFDI provides maps of microscopic structural biomarkers that cannot be obtained with diffuse wide-field imaging and characterizes spatial variations not resolved by point-based optical sampling.

  4. MR imaging of renal cortical tumours: qualitative and quantitative chemical shift imaging parameters.

    Science.gov (United States)

    Karlo, Christoph A; Donati, Olivio F; Burger, Irene A; Zheng, Junting; Moskowitz, Chaya S; Hricak, Hedvig; Akin, Oguz

    2013-06-01

    To assess qualitative and quantitative chemical shift MRI parameters of renal cortical tumours. A total of 251 consecutive patients underwent 1.5-T MRI before nephrectomy. Two readers (R1, R2) independently evaluated all tumours visually for a decrease in signal intensity (SI) on opposed- compared with in-phase chemical shift images. In addition, SI was measured on in- and opposed-phase images (SI(IP), SI(OP)) and the chemical shift index was calculated as a measure of percentage SI change. Histopathology served as the standard of reference. A visual decrease in SI was identified significantly more often in clear cell renal cell carcinoma (RCCs) (R1, 73 %; R2, 64 %) and angiomyolipomas (both, 80 %) than in oncocytomas (29 %, 12 %), papillary (29 %, 17 %) and chromophobe RCCs (13 %, 9 %; all, P chemical shift index was significantly greater in clear cell RCC and angiomyolipoma than in the other histological subtypes (both, P analysis (concordance correlation coefficient, 0.80). A decrease in SI on opposed-phase chemical shift images is not an identifying feature of clear cell RCCs or angiomyolipomas, but can also be observed in oncocytomas, papillary and chromophobe RCCs. After excluding angiomyolipomas, a decrease in SI of more than 25 % was diagnostic for clear cell RCCs. • Chemical shift MRI offers new information about fat within renal tumours. • Opposed-phase signal decrease can be observed in all renal cortical tumours. • A greater than 25 % decrease in signal appears to be diagnostic for clear cell RCCs.

  5. Quantitative image analysis in the assessment of diffuse large B-cell lymphoma.

    Science.gov (United States)

    Chabot-Richards, Devon S; Martin, David R; Myers, Orrin B; Czuchlewski, David R; Hunt, Kristin E

    2011-12-01

    Proliferation rates in diffuse large B-cell lymphoma have been associated with conflicting outcomes in the literature, more often with high proliferation associated with poor prognosis. In most studies, the proliferation rate was estimated by a pathologist using an immunohistochemical stain for the monoclonal antibody Ki-67. We hypothesized that a quantitative image analysis algorithm would give a more accurate estimate of the proliferation rate, leading to better associations with survival. In all, 84 cases of diffuse large B-cell lymphoma were selected according to the World Health Organization criteria. Ki-67 percentage positivity estimated by the pathologist was recorded from the original report. The same slides were then scanned using an Aperio ImageScope, and Ki-67 percentage positivity was calculated using a computer-based quantitative immunohistochemistry nuclear algorithm. In addition, chart review was performed and survival time was recorded. The Ki-67 percentage estimated by the pathologist from the original report versus quantitative image analysis was significantly correlated (Pquantitative image analysis (P=0.021). There was less agreement at lower Ki-67 percentages. Comparison of Ki-67 percentage positivity versus survival did not show significant association either with pathologist estimate or quantitative image analysis. However, although not significant, there was a trend of worse survival at higher proliferation rates detected by the pathologist but not by quantitative image analysis. Interestingly, our data suggest that the Ki-67 percentage positivity as assessed by the pathologist may be more closely associated with survival outcome than that identified by quantitative image analysis. This may indicate that pathologists are better at selecting appropriate areas of the slide. More cases are needed to assess whether this finding would be statistically significant. Due to the good correlation between pathologist estimate and quantitative image

  6. Molecular Imaging with Small Animal PET/CT

    DEFF Research Database (Denmark)

    2011-01-01

    in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements...... is also described. In addition, the non-invasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small...

  7. Molecular imaging true-colour spectroscopic optical coherence tomography

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

  9. Single-exposure quantitative phase imaging in color-coded LED microscopy (Conference Presentation)

    Science.gov (United States)

    Lee, Wonchan; Jung, Daeseong; Joo, Chulmin

    2017-02-01

    Quantitative phase-gradient or phase imaging in LED microscopy has been recently demonstrated. The methods enable measurement of phase distribution of transparent specimens in a simple and cost-effective manner, but require multiple image acquisitions with different source or pupil configurations to improve phase accuracy. Here, we demonstrate a strategy for single-shot quantitative phase imaging in color-coded LED microscopy. We employ a circular LED illumination pattern that is trisected into subregions with equal area, assigned to red, green and blue colors, respectively. Additional color filter is also employed to mitigate the color leakage of light into different color channels of the image sensor. Image acquisition with a color image sensor and subsequent computation based on the weak object transfer function allow for quantitative amplitude and phase measurements of a specimen. We describe computational model and single-shot quantitative phase imaging capability of our method by presenting phase images of calibrated phase sample and dynamics of cells. Phase measurement accuracy is validated with pre-characterized phase plate, and single-shot phase imaging capability is demonstrated with time-lapse imaging of cells acquired at 30 Hz.

  10. Quantitative imaging of collective cell migration during Drosophila gastrulation: multiphoton microscopy and computational analysis

    OpenAIRE

    Supatto, Willy; McMahon, Amy; Fraser, Scott E.; Stathopoulos, Angelike

    2009-01-01

    This protocol describes imaging and computational tools to collect and analyze live imaging data of embryonic cell migration. Our five-step protocol requires a few weeks to move through embryo preparation and four-dimensional (4D) live imaging using multiphoton microscopy, to 3D cell tracking using image processing, registration of tracking data and their quantitative analysis using computational tools. It uses commercially available equipment and requires expertise in microscopy and progr...

  11. A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

    Science.gov (United States)

    Vreysen, Samme; Scheyltjens, Isabelle; Laramée, Marie-Eve; Arckens, Lutgarde

    2017-01-01

    Several techniques, allowing the reconstruction and visualization of functional, anatomical or molecular information from tissue and organ slices, have been developed over the years. Yet none allow direct comparison without reprocessing the same slices. Alternative methods using publicly available reference maps like the Allen Brain Atlas lack flexibility with respect to age and species. We propose a new approach to reconstruct a segmented region of interest from serial slices by projecting the optical density values representing a given molecular signal to a plane of view of choice, and to generalize the results into a reference map, which is built from the individual maps of all animals under study. Furthermore, to allow quantitative comparison between experimental conditions, a non-parametric pseudo t-test has been implemented. This new mapping tool was applied, optimized and validated making use of an in situ hybridization dataset that represents the spatiotemporal expression changes for the neuronal activity reporter gene zif268, in relation to cortical plasticity induced by monocular enucleation, covering the entire mouse visual cortex. The created top view maps of the mouse brain allow precisely delineating and interpreting 11 extrastriate areas surrounding mouse V1. As such, and because of the opportunity to create a planar projection of choice, these molecular maps can in the future easily be compared with functional or physiological imaging maps created with other techniques such as Ca2+, flavoprotein and optical imaging. PMID:28144216

  12. Molecular imaging of angiogenesis with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, Ingrid; Boerman, Otto C. [Radboud University Nijmegen Medical Center, Department of Nuclear Medicine, P.O. Box 9101, HB Nijmegen (Netherlands)

    2010-08-15

    Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: {sup 99m}Tc (E{sub max} 141 keV, T{sub 1/2} 6.02 h), {sup 123}I (E{sub max} 529 keV, T{sub 1/2} 13.0 h) and {sup 111}In (E{sub max} 245 keV, T{sub 1/2} 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed. (orig.)

  13. Modeling quantitative phase image formation under tilted illuminations.

    Science.gov (United States)

    Bon, Pierre; Wattellier, Benoit; Monneret, Serge

    2012-05-15

    A generalized product-of-convolution model for simulation of quantitative phase microscopy of thick heterogeneous specimen under tilted plane-wave illumination is presented. Actual simulations are checked against a much more time-consuming commercial finite-difference time-domain method. Then modeled data are compared with experimental measurements that were made with a quadriwave lateral shearing interferometer.

  14. Measuring dynamic membrane fluctuations in cell membrane using quantitative phase imaging (Conference Presentation)

    Science.gov (United States)

    Lee, SangYun; Kim, Kyoohyun; Park, YongKeun

    2017-02-01

    There is a strong correlation between the dynamic membrane fluctuations and the biomechanical properties of living cells. The dynamic membrane fluctuation consists of submicron displacements, and can be altered by changing the cells' pathophysiological conditions. These results have significant relevance to the understanding of RBC biophysics and pathology, as follows. RBCs must withstand large mechanical deformations during repeated passages through the microvasculature and the fenestrated walls of the splenic sinusoids. This essential ability is diminished with senescence, resulting in physiological destruction of the aging RBCs. Pathological destruction of the red cells, however, occurs in cells affected by a host of diseases such as spherocytosis, malaria, and Sickle cell disease, as RBCs depart from their normal discoid shape and lose their deformability. Therefore, quantifying the RBC deformability insight into a variety of problems regarding the interplay of cell structure, dynamics, and function. Furthermore, the ability to monitor mechanical properties of RBCs is of vital interest in monitoring disease progression or response to treatment as molecular and pharmaceutical approaches for treatment of chronic diseases. Here, we present the measurements of dynamic membrane fluctuations in live cells using quantitative phase imaging techniques. Measuring both the 3-D refractive index maps and the dynamic phase images of live cells are simultaneously measured, from which dynamic membrane fluctuation and deformability of cells are precisely calculated. We also present its applications to various diseases ranging from sickle cell diseases, babesiosis, and to diabetes.

  15. Quantitative second-harmonic generation imaging to detect osteogenesis imperfecta in human skin samples

    Science.gov (United States)

    Adur, J.; Ferreira, A. E.; D'Souza-Li, L.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Baratti, M. O.; Carvalho, H. F.; Cesar, C. L.

    2012-03-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that leads to bone fractures due to mutations in the Col1A1 or Col1A2 genes that affect the primary structure of the collagen I chain with the ultimate outcome in collagen I fibrils that are either reduced in quantity or abnormally organized in the whole body. A quick test screening of the patients would largely reduce the sample number to be studied by the time consuming molecular genetics techniques. For this reason an assessment of the human skin collagen structure by Second Harmonic Generation (SHG) can be used as a screening technique to speed up the correlation of genetics/phenotype/OI types understanding. In the present work we have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization of the OI human skin samples comparing with normal control patients. By comparing fibril collagen distribution and spatial organization, we calculated the anisotropy and texture patterns of this structural protein. The analysis of the anisotropy was performed by means of the two-dimensional Discrete Fourier Transform and image pattern analysis with Gray-Level Co-occurrence Matrix (GLCM). From these results, we show that statistically different results are obtained for the normal and disease states of OI.

  16. The reproducibility of quantitative measurements in lumbar magnetic resonance imaging of children from the general population

    DEFF Research Database (Denmark)

    Masharawi, Y; Kjær, Per; Bendix, T

    2008-01-01

    STUDY DESIGN: Quantitative lumbar magnetic resonance imaging (MRI) measurements in children were taken twice and analyzed for intra- and intertester reproducibility. OBJECTIVE: To evaluate the reproducibility of a variety of lumbar quantitative measurements taken from MRIs of children from the ge...

  17. Quantitative Imaging Biomarkers: A Review of Statistical Methods for Computer Algorithm Comparisons

    OpenAIRE

    2014-01-01

    Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare ...

  18. Quantitative image analysis of microstructure development during pressure sintering of CoO

    Energy Technology Data Exchange (ETDEWEB)

    Miro, A; Notis, M R

    1979-01-01

    An automatic system for quantitative image analysis was developed to study the transition from intermediate to final stage pore structure in pressure-sintered CoO. One of the significant results from this study indicates that the projected length is a good parameter to observe the transition from open cylindrical to closed porosity. Quantitative image analysis indicates that the Zener relationship (r/G approx. P) is obeyed through the entire sintering process.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  20. Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment.

    Science.gov (United States)

    Raunig, David L; McShane, Lisa M; Pennello, Gene; Gatsonis, Constantine; Carson, Paul L; Voyvodic, James T; Wahl, Richard L; Kurland, Brenda F; Schwarz, Adam J; Gönen, Mithat; Zahlmann, Gudrun; Kondratovich, Marina V; O'Donnell, Kevin; Petrick, Nicholas; Cole, Patricia E; Garra, Brian; Sullivan, Daniel C

    2015-02-01

    Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Advances of Molecular Imaging in Epilepsy.

    Science.gov (United States)

    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.

  2. Quantitative, Noninvasive Imaging of DNA Damage in Vivo of Prostate Cancer Therapy by Transurethral Photoacoustic (TUPA) Imaging

    Science.gov (United States)

    2014-10-01

    Photoacoustic (TUPA) Imaging PRINCIPAL INVESTIGATOR: Liangzhong Xiang CONTRACTING ORGANIZATION: The Leland Stanford Junior University Stanford, CA...NUMBER Prostate Cancer Therapy by Transurethral Photoacoustic Imaging 5b. GRANT NUMBER W81XWH-13-1-0481 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... Photoacoustic (TUPA) Imaging, which utilizing a small catheter into the urethra enabling imaging molecular marker of DNA Damage during prostate radiation

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

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

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

  4. Quantitative Imaging in Radiation Oncology: An Emerging Science and Clinical Service.

    Science.gov (United States)

    Jaffray, David Anthony; Chung, Caroline; Coolens, Catherine; Foltz, Warren; Keller, Harald; Menard, Cynthia; Milosevic, Michael; Publicover, Julia; Yeung, Ivan

    2015-10-01

    Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose-positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. These are reviewed with an effort to highlight challenges related to quantification and reproducibility. In addition, several of the emerging applications of these imaging approaches are also highlighted. Finally, the growing community of support for establishing quantitative imaging approaches as we move toward clinical evaluation is summarized and the need for a clinical service in support of the clinical science and delivery of care is proposed. Copyright © 2015. Published by Elsevier Inc.

  5. Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

    Science.gov (United States)

    Buckler, Andrew J; Bresolin, Linda; Dunnick, N Reed; Sullivan, Daniel C; Aerts, Hugo J W L; Bendriem, Bernard; Bendtsen, Claus; Boellaard, Ronald; Boone, John M; Cole, Patricia E; Conklin, James J; Dorfman, Gary S; Douglas, Pamela S; Eidsaunet, Willy; Elsinger, Cathy; Frank, Richard A; Gatsonis, Constantine; Giger, Maryellen L; Gupta, Sandeep N; Gustafson, David; Hoekstra, Otto S; Jackson, Edward F; Karam, Lisa; Kelloff, Gary J; Kinahan, Paul E; McLennan, Geoffrey; Miller, Colin G; Mozley, P David; Muller, Keith E; Patt, Rick; Raunig, David; Rosen, Mark; Rupani, Haren; Schwartz, Lawrence H; Siegel, Barry A; Sorensen, A Gregory; Wahl, Richard L; Waterton, John C; Wolf, Walter; Zahlmann, Gudrun; Zimmerman, Brian

    2011-06-01

    Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1. RSNA, 2011

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Molecular imaging: a new approach to nuclear cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Dobrucki, L.W.; Sinusas, A.J. [Yale Univ. School of Medicine, New Haven (United States). Section of Cardiovascular Medicine, Department of Internal Medicine

    2005-03-01

    Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. 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 instrumentations 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 therapeutical angiogenesis.

  9. A collaborative enterprise for multi-stakeholder participation in the advancement of quantitative imaging.

    Science.gov (United States)

    Buckler, Andrew J; Bresolin, Linda; Dunnick, N Reed; Sullivan, Daniel C

    2011-03-01

    Medical imaging has seen substantial and rapid technical advances during the past decade, including advances in image acquisition devices, processing and analysis software, and agents to enhance specificity. Traditionally, medical imaging has defined anatomy, but increasingly newer, more advanced, imaging technologies provide biochemical and physiologic information based on both static and dynamic modalities. These advanced technologies are important not only for detecting disease but for characterizing and assessing change of disease with time or therapy. Because of the rapidity of these advances, research to determine the utility of quantitative imaging in either clinical research or clinical practice has not had time to mature. Methods to appropriately develop, assess, regulate, and reimburse must be established for these advanced technologies. Efficient and methodical processes that meet the needs of stakeholders in the biomedical research community, therapeutics developers, and health care delivery enterprises will ultimately benefit individual patients. To help address this, the authors formed a collaborative program-the Quantitative Imaging Biomarker Alliance. This program draws from the very successful precedent set by the Integrating the Healthcare Enterprise effort but is adapted to the needs of imaging science. Strategic guidance supporting the development, qualification, and deployment of quantitative imaging biomarkers will lead to improved standardization of imaging tests, proof of imaging test performance, and greater use of imaging to predict the biologic behavior of tissue and monitor therapy response. These, in turn, confer value to corporate stakeholders, providing incentives to bring new and innovative products to market.

  10. Groping for Quantitative Digital 3-D Image Analysis: An Approach to Quantitative Fluorescence In Situ Hybridization in Thick Tissue Sections of Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Karsten Rodenacker

    1997-01-01

    Full Text Available In molecular pathology numerical chromosome aberrations have been found to be decisive for the prognosis of malignancy in tumours. The existence of such aberrations can be detected by interphase fluorescence in situ hybridization (FISH. The gain or loss of certain base sequences in the desoxyribonucleic acid (DNA can be estimated by counting the number of FISH signals per cell nucleus. The quantitative evaluation of such events is a necessary condition for a prospective use in diagnostic pathology. To avoid occlusions of signals, the cell nucleus has to be analyzed in three dimensions. Confocal laser scanning microscopy is the means to obtain series of optical thin sections from fluorescence stained or marked material to fulfill the conditions mentioned above. A graphical user interface (GUI to a software package for display, inspection, count and (semi‐automatic analysis of 3‐D images for pathologists is outlined including the underlying methods of 3‐D image interaction and segmentation developed. The preparative methods are briefly described. Main emphasis is given to the methodical questions of computer‐aided analysis of large 3‐D image data sets for pathologists. Several automated analysis steps can be performed for segmentation and succeeding quantification. However tumour material is in contrast to isolated or cultured cells even for visual inspection, a difficult material. For the present a fully automated digital image analysis of 3‐D data is not in sight. A semi‐automatic segmentation method is thus presented here.

  11. Emerging applications of conjugated polymers in molecular imaging.

    Science.gov (United States)

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

    2013-10-28

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

  12. Automatic segmentation method of striatum regions in quantitative susceptibility mapping images

    Science.gov (United States)

    Murakawa, Saki; Uchiyama, Yoshikazu; Hirai, Toshinori

    2015-03-01

    Abnormal accumulation of brain iron has been detected in various neurodegenerative diseases. Quantitative susceptibility mapping (QSM) is a novel contrast mechanism in magnetic resonance (MR) imaging and enables the quantitative analysis of local tissue susceptibility property. Therefore, automatic segmentation tools of brain regions on QSM images would be helpful for radiologists' quantitative analysis in various neurodegenerative diseases. The purpose of this study was to develop an automatic segmentation and classification method of striatum regions on QSM images. Our image database consisted of 22 QSM images obtained from healthy volunteers. These images were acquired on a 3.0 T MR scanner. The voxel size was 0.9×0.9×2 mm. The matrix size of each slice image was 256×256 pixels. In our computerized method, a template mating technique was first used for the detection of a slice image containing striatum regions. An image registration technique was subsequently employed for the classification of striatum regions in consideration of the anatomical knowledge. After the image registration, the voxels in the target image which correspond with striatum regions in the reference image were classified into three striatum regions, i.e., head of the caudate nucleus, putamen, and globus pallidus. The experimental results indicated that 100% (21/21) of the slice images containing striatum regions were detected accurately. The subjective evaluation of the classification results indicated that 20 (95.2%) of 21 showed good or adequate quality. Our computerized method would be useful for the quantitative analysis of Parkinson diseases in QSM images.

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

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

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

  14. Real-time quantitative nicking endonuclease-mediated isothermal amplification with small molecular beacons.

    Science.gov (United States)

    Xu, Wentao; Wang, Chenguang; Zhu, Pengyu; Guo, Tianxiao; Xu, Yuancong; Huang, Kunlun; Luo, Yunbo

    2016-04-21

    Techniques of isothermal amplification have recently made great strides, and have generated significant interest in the field of point-of-care detection. Nicking endonuclease-mediated isothermal amplification (NEMA) is an example of simple isothermal technology. In this paper, a real-time quantitative nicking endonuclease-mediated isothermal amplification with small molecular beacons (SMB-NEMA) of improved specificity and sensitivity is described. First, we optimized the prohibition of de novo synthesis by choosing Nt·BstNBI endonuclease. Second, the whole genome was successfully amplified with Nt·BstNBI (6 U), betaine (1 M) and trehalose (60 mM) for the first time. Third, we achieved 10 pg sensitivity for the first time after adding a small molecular beacon that spontaneously undergoes a conformational change when hybridizing to target, and the practical test validated the assay's application. The small molecular beacon has a similar melting temperature to the reaction temperature, but is approximately 10 bp shorter than the length of a traditional molecular beacon. A new threshold regulation was also established for isothermal conditions. Finally, we established a thermodynamic model for designing small molecular beacons. This multistate model is more correct than the traditional algorithm. This theoretical and practical basis will help us to monitor SMB-NEMA in a quantitative way. In summary, our SMB-NEMA method allows the simple, specific and sensitive assessment of isothermal DNA quantification.

  15. Quantitative Computed Tomography and image analysis for advanced muscle assessment

    Directory of Open Access Journals (Sweden)

    Kyle Joseph Edmunds

    2016-06-01

    Full Text Available Medical imaging is of particular interest in the field of translational myology, as extant literature describes the utilization of a wide variety of techniques to non-invasively recapitulate and quantity various internal and external tissue morphologies. In the clinical context, medical imaging remains a vital tool for diagnostics and investigative assessment. This review outlines the results from several investigations on the use of computed tomography (CT and image analysis techniques to assess muscle conditions and degenerative process due to aging or pathological conditions. Herein, we detail the acquisition of spiral CT images and the use of advanced image analysis tools to characterize muscles in 2D and 3D. Results from these studies recapitulate changes in tissue composition within muscles, as visualized by the association of tissue types to specified Hounsfield Unit (HU values for fat, loose connective tissue or atrophic muscle, and normal muscle, including fascia and tendon. We show how results from these analyses can be presented as both average HU values and compositions with respect to total muscle volumes, demonstrating the reliability of these tools to monitor, assess and characterize muscle degeneration.

  16. Quantitative imaging and measurement of cell-substrate surface deformation by digital holography

    Science.gov (United States)

    Yu, Xiao; Cross, Michael; Liu, Changgeng; Clark, David C.; Haynie, Donald T.; Kim, Myung K.

    2012-10-01

    Quantitative phase microscopy by digital holography (DH-QPM) is introduced to study the cell-substrate interactions and migratory behavior of adhesive cells. A non-wrinkling elastic substrate, collagen-coated polyacrylamide (PAA) has been employed and its surface deformation due to cell adhesion and motility has been visualized as certain tangential and vertical displacement and distortion. The surface deformation on substrates of different elasticity and thickness has been quantitatively imaged and the corresponding cellular traction force of motile fibroblasts has been measured from phase profiles by DH-QPM. DH-QPM is able to yield quantitative measures directly and provide efficient and versatile means for quantitatively analyzing cellular motility.

  17. 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.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

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

  19. Quantitative whole body biodistribution of fluorescent-labeled agents by non-invasive tomographic imaging.

    Directory of Open Access Journals (Sweden)

    Kristine O Vasquez

    Full Text Available When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR or near infrared (NIR imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D fluorescence reflectance imaging of excised intact organs (r²  =  0.996 and 0.969, respectively. Dynamic FMT imaging (multiple times from 0 to 24 h performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20-50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor

  20. Quantitative image analysis for the detection of motion artefacts in coronary artery computed tomography

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M.; Dikkers, Riksta; Greuter, Marcel J.; Zijlstra, Felix; Oudkerk, Matthijs

    2010-01-01

    Multi detector-row CT (MDCT), the current preferred method for coronary artery disease assessment, is still affected by motion artefacts. To rule out motion artefacts, qualitative image analysis is usually performed. Our study aimed to develop a quantitative image analysis for motion artefacts detec

  1. Quantitative comparison of OSEM and penalized likelihood image reconstruction using relative difference penalties for clinical PET.

    Science.gov (United States)

    Ahn, Sangtae; Ross, Steven G; Asma, Evren; Miao, Jun; Jin, Xiao; Cheng, Lishui; Wollenweber, Scott D; Manjeshwar, Ravindra M

    2015-08-07

    Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post-filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs.

  2. Quantitative 3-D imaging topogrammetry for telemedicine applications

    Science.gov (United States)

    Altschuler, Bruce R.

    1994-01-01

    The technology to reliably transmit high-resolution visual imagery over short to medium distances in real time has led to the serious considerations of the use of telemedicine, telepresence, and telerobotics in the delivery of health care. These concepts may involve, and evolve toward: consultation from remote expert teaching centers; diagnosis; triage; real-time remote advice to the surgeon; and real-time remote surgical instrument manipulation (telerobotics with virtual reality). Further extrapolation leads to teledesign and telereplication of spare surgical parts through quantitative teleimaging of 3-D surfaces tied to CAD/CAM devices and an artificially intelligent archival data base of 'normal' shapes. The ability to generate 'topogrames' or 3-D surface numerical tables of coordinate values capable of creating computer-generated virtual holographic-like displays, machine part replication, and statistical diagnostic shape assessment is critical to the progression of telemedicine. Any virtual reality simulation will remain in 'video-game' realm until realistic dimensional and spatial relational inputs from real measurements in vivo during surgeries are added to an ever-growing statistical data archive. The challenges of managing and interpreting this 3-D data base, which would include radiographic and surface quantitative data, are considerable. As technology drives toward dynamic and continuous 3-D surface measurements, presenting millions of X, Y, Z data points per second of flexing, stretching, moving human organs, the knowledge base and interpretive capabilities of 'brilliant robots' to work as a surgeon's tireless assistants becomes imaginable. The brilliant robot would 'see' what the surgeon sees--and more, for the robot could quantify its 3-D sensing and would 'see' in a wider spectral range than humans, and could zoom its 'eyes' from the macro world to long-distance microscopy. Unerring robot hands could rapidly perform machine-aided suturing with

  3. Current research in nuclear medicine and molecular imaging in Italy: highlights of the 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging.

    Science.gov (United States)

    Cuocolo, A

    2011-06-01

    The 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN) took place in Rimini on March 18-21, 2011 under the chairmanship of Professor Stefano Fanti. The program was of excellent quality and put a further step for the settlement of the standardized AIMN congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success with more than 1100 total participants and more than 360 abstracts received. Of these, 40 abstracts were accepted for oral and 285 for poster presentations. The original investigations presented were related to different areas of nuclear medicine and molecular imaging, with particular focus on advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in well established areas of clinical application, such as oncology, cardiology, neurology, psychiatry, endocrinology, paediatrics, and infection and inflammation. Noteworthy, several presentations at this congress, focusing on quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, identified when nuclear medicine procedures achieved clinical effectiveness for patient care and patient management and further demonstrated that nuclear medicine plays a crucial role in the contemporary medical scenario. This highlights lecture is only a brief summary of the large amount of data presented and discussed, which can be found in much greater detail in the congress abstract book, published as volume 55, supplement 1 of the Q J Nucl Med Mol Imaging in April 2011.

  4. Molecular imaging using sodium iodide symporter (NIS)

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-04-01

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

  5. Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

    OpenAIRE

    Fangfang Chao; Yehua Shen; Hong Zhang; Mei Tian

    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, longit...

  6. Microscopic identification of Chinese medicinal materials based on X-ray phase contrast imaging: from qualitative to quantitative

    Science.gov (United States)

    Xue, Y.; Liang, Z.; Tan, H.; Ni, L.; Zhao, Z.; Xiao, T.; Xu, H.

    2016-07-01

    Although a variety of methods, ranging from simple morphological examination to physical and chemical analysis, and DNA molecular biology, exist for authenticating Chinese medicinal materials(CMMs), no methods can achieve both the source species identification and quality evaluation of CMMs simultaneously. Furthermore, the methods that are currently available for the identification of CMMs, including both optical and electronic microscopy, usually entail strict requirements for sample preparation or testing environment, such as the slicing of super-thin sections, or processing with specific chemical reagents. These treatments not only damage the CMMs but may also cause some of the original microstructures to be missed. Additionally, they may even yield false results. Owing to the unique penetrating character of X-rays, X-ray phase contrast imaging(XPCI) can be used to realize the inner microstructures of CMMs through nondestructive imaging. With the higher flux and luminance of the third generation of synchrotron radiation facility, XPCI can provides clearer and finer microstructures of CMMs, which are mainly composed of C, H, O, and N elements, with better spatial and density resolutions. For more than ten years, the X-ray imaging group at the Shanghai Institute of Applied Physics has investigated the microstructures of CMMs by XPCI and they have established and developed a quantitative X-ray phase contrast micro-CT for investigating the characteristic microstructures of CMMs. During this period, a variety of typical CMMs have been investigated, from two-dimensional (2D) radiography to three-dimensional (3D) micro-CT, from qualitative to quantitative. Taken together, these results verify that quantitative X-ray phase contrast micro-CT is a practical tool for the microscopic investigation of CMMs. Additionally, further efforts are being made to find the relationship between the microstructures' quantitative factors and active chemical components. At present

  7. Quantitative assessment of brain perfusion with magnetic resonance imaging

    NARCIS (Netherlands)

    Bleeker, Egbert Jan Willem

    2011-01-01

    This thesis focuses on assessing blood supply to brain tissue using MRI. For Dynamic Susceptibility Contrast-MRI a series of images is acquired during the passage of a bolus contrast agent through the brain up to the point that the contrast agent is equally mixed within the total blood pool. The tis

  8. Ultrasound imaging for quantitative measurement of immersed plastic waste particles

    NARCIS (Netherlands)

    Sanaee, S.A.; Bakker, M.C.M.

    2012-01-01

    Ultrasound imaging techniques are proposed for measuring the shape and thickness of immersed waste particles (10-20 mm size) using a linear sensor array from a fixed position. For these purposes both the front and back surface of a particle needs to be reconstructed. Raw ultrasound pulse-echo and pl

  9. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  10. Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle

    Directory of Open Access Journals (Sweden)

    Kevin J. Black

    2013-08-01

    Full Text Available Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC50 (the concentration of drug that produces half the maximum possible effect. We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, rapid quantitative pharmacodynamic imaging reliably estimates EC50 from the simulated data, except when noise overwhelms the drug effect or when the effect occurs only at high doses. In preliminary fMRI studies of primate brain using a dopamine agonist, the observed noise level is modest compared with observed drug effects, and a quantitative EC50 can be obtained from some regional time-signal curves. Taken together, these results suggest that research and clinical applications for rapid quantitative pharmacodynamic imaging are realistic.

  11. Generalized eikonal of partially coherent beams and its use in quantitative imaging.

    Science.gov (United States)

    Gureyev, T E; Paganin, D M; Stevenson, A W; Mayo, S C; Wilkins, S W

    2004-08-06

    The generalized eikonal of a partially coherent paraxial wave is introduced via a differential equation describing the evolution of the time-averaged intensity. The theoretical formalism provides an analytical tool for the study of partially coherent imaging systems. It also makes possible quantitative phase retrieval and compositional mapping of weakly absorbing samples using phase-contrast imaging with broadband polychromatic radiation of known spectral distribution. An experimental demonstration is presented of the quantitative reconstruction of the projected thickness of a sample, given a phase-contrast image obtained using a polychromatic microfocus x-ray source.

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

    Directory of Open Access Journals (Sweden)

    Misha Pivovarov

    2005-10-01

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

  13. Quantitative appraisal for noise reduction in digital holographic phase imaging.

    Science.gov (United States)

    Montresor, Silvio; Picart, Pascal

    2016-06-27

    This paper discusses on a quantitative comparison of the performances of different advanced algorithms for phase data de-noising. In order to quantify the performances, several criteria are proposed: the gain in the signal-to-noise ratio, the Q index, the standard deviation of the phase error, and the signal to distortion ratio. The proposed methodology to investigate de-noising algorithms is based on the use of a realistic simulation of noise-corrupted phase data. A database including 25 fringe patterns divided into 5 patterns and 5 different signal-to-noise ratios was generated to evaluate the selected de-noising algorithms. A total of 34 algorithms divided into different families were evaluated. Quantitative appraisal leads to ranking within the considered criteria. A fairly good correlation between the signal-to-noise ratio gain and the quality index has been observed. There exists an anti-correlation between the phase error and the quality index which indicates that the phase errors are mainly structural distortions in the fringe pattern. Experimental results are thoroughly discussed in the paper.

  14. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

  16. Molecular imaging of cell-mediated cancer immunotherapy.

    Science.gov (United States)

    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.

  17. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants

    Indian Academy of Sciences (India)

    Alice Kujur; Maneesha S Saxena; Deepak Bajaj; Laxmi; Swarup K Parida

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world’s food security. To improve the productivity and sustainability of agriculture, the development of high-yielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern –omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  18. Simultaneous molecular and anatomical imaging of the mouse in vivo.

    Science.gov (United States)

    Goertzen, Andrew L; Meadors, A Ken; Silverman, Robert W; Cherry, Simon R

    2002-12-21

    Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice.

  19. Off-axis quantitative phase imaging processing using CUDA: toward real-time applications.

    Science.gov (United States)

    Pham, Hoa; Ding, Huafeng; Sobh, Nahil; Do, Minh; Patel, Sanjay; Popescu, Gabriel

    2011-07-01

    We demonstrate real time off-axis Quantitative Phase Imaging (QPI) using a phase reconstruction algorithm based on NVIDIA's CUDA programming model. The phase unwrapping component is based on Goldstein's algorithm. By mapping the process of extracting phase information and unwrapping to GPU, we are able to speed up the whole procedure by more than 18.8× with respect to CPU processing and ultimately achieve video rate for mega-pixel images. Our CUDA implementation also supports processing of multiple images simultaneously. This enables our imaging system to support high speed, high throughput, and real-time image acquisition and visualization.

  20. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-01

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

  1. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-01

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

  2. Statistical Methods for Quantitatively Detecting Fungal Disease from Fruits’ Images

    OpenAIRE

    Jagadeesh D. Pujari; Yakkundimath, Rajesh Siddaramayya; Byadgi, Abdulmunaf Syedhusain

    2013-01-01

    In this paper we have proposed statistical methods for detecting fungal disease and classifying based on disease severity levels.  Most fruits diseases are caused by bacteria, fungi, virus, etc of which fungi are responsible for a large number of diseases in fruits. In this study images of fruits, affected by different fungal symptoms are collected and categorized based on disease severity. Statistical features like block wise, gray level co-occurrence matrix (GLCM), gray level runlength matr...

  3. Quantitative imaging of excised osteoarthritic cartilage using spectral CT

    Energy Technology Data Exchange (ETDEWEB)

    Rajendran, Kishore; Bateman, Christopher J.; Younis, Raja Aamir; De Ruiter, Niels J.A.; Ramyar, Mohsen; Anderson, Nigel G. [University of Otago - Christchurch, Department of Radiology, Christchurch (New Zealand); Loebker, Caroline [University of Otago, Christchurch Regenerative Medicine and Tissue Engineering Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, Christchurch (New Zealand); University of Twente, Department of Developmental BioEngineering, Enschede (Netherlands); Schon, Benjamin S.; Hooper, Gary J.; Woodfield, Tim B.F. [University of Otago, Christchurch Regenerative Medicine and Tissue Engineering Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, Christchurch (New Zealand); Chernoglazov, Alex I. [University of Canterbury, Human Interface Technology Laboratory New Zealand, Christchurch (New Zealand); Butler, Anthony P.H. [University of Otago - Christchurch, Department of Radiology, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); MARS Bioimaging, Christchurch (New Zealand)

    2017-01-15

    To quantify iodine uptake in articular cartilage as a marker of glycosaminoglycan (GAG) content using multi-energy spectral CT. We incubated a 25-mm strip of excised osteoarthritic human tibial plateau in 50 % ionic iodine contrast and imaged it using a small-animal spectral scanner with a cadmium telluride photon-processing detector to quantify the iodine through the thickness of the articular cartilage. We imaged both spectroscopic phantoms and osteoarthritic tibial plateau samples. The iodine distribution as an inverse marker of GAG content was presented in the form of 2D and 3D images after applying a basis material decomposition technique to separate iodine in cartilage from bone. We compared this result with a histological section stained for GAG. The iodine in cartilage could be distinguished from subchondral bone and quantified using multi-energy CT. The articular cartilage showed variation in iodine concentration throughout its thickness which appeared to be inversely related to GAG distribution observed in histological sections. Multi-energy CT can quantify ionic iodine contrast (as a marker of GAG content) within articular cartilage and distinguish it from bone by exploiting the energy-specific attenuation profiles of the associated materials. (orig.)

  4. Schlieren imaging of microthruster exhausts for qualitative and quantitative analysis

    Science.gov (United States)

    Lekholm, Ville; Palmer, Kristoffer; Thornell, Greger

    2012-08-01

    Schlieren imaging is a method used to visualize differences in refractive index within a medium. It is a powerful and straightforward tool for sensitive and high-resolution visualization of, e.g., gas flows. Here, heated cold gas microthrusters were studied with this technique. The thrusters are manufactured using microelectromechanical systems technology and measure 22 × 22 × 0.85 mm3. The nozzles are approximately 20 µm wide at the throat and 350 µm wide at the exit. Through these studies, verification of the functionality of the thrusters and direct visualization of the thruster exhausts were possible. At atmospheric pressure, slipping of the exhaust was observed, due to severe overexpansion of the nozzle. In vacuum (3 kPa), the exhaust was imaged while feed pressure was varied from 100 to 450 kPa. The nozzle was overexpanded, and the flow was seen to be supersonic. The shock cell period, ranging from 320 to 610 µm, was linearly dependent on feed pressure. With activated heaters, the shock cell separation increased. The effect of the heaters was more prominent at low feed pressure, and an increase in specific impulse of 20% was calculated. It was also shown that schlieren imaging can be used to detect leaks, making it a valuable, safe and noninvasive aid in quality control of the thrusters.

  5. In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhuo, Shuangmu, E-mail: shuangmuzhuo@gmail.com, E-mail: hanry-yu@nuhs.edu.sg [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou 350007 (China); Yan, Jie [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, MD 11 #04-01A, 117599 Singapore (Singapore); Kang, Yuzhan [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Xu, Shuoyu [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Peng, Qiwen [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Mechanobiology Institute, 5A Engineering Drive 1, T-Lab #05-01, 117411 Singapore (Singapore); and others

    2014-07-14

    Various structural features on the liver surface reflect functional changes in the liver. The visualization of these surface features with molecular specificity is of particular relevance to understanding the physiology and diseases of the liver. Using multi-photon microscopy (MPM), we have developed a label-free, three-dimensional quantitative and sensitive method to visualize various structural features of liver surface in living rat. MPM could quantitatively image the microstructural features of liver surface with respect to the sinuosity of collagen fiber, the elastic fiber structure, the ratio between elastin and collagen, collagen content, and the metabolic state of the hepatocytes that are correlative with the pathophysiologically induced changes in the regions of interest. This study highlights the potential of this technique as a useful tool for pathophysiological studies and possible diagnosis of the liver diseases with further development.

  6. Molecular Imaging of the ATM Kinase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Terence M. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Nyati, Shyam [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Ross, Brian D. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Rehemtulla, Alnawaz, E-mail: alnawaz@umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2013-08-01

    Purpose: Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including from DNA double-strand breaks. ATM activation results in the initiation of a complex cascade of events including DNA damage repair, cell cycle checkpoint control, and survival. We sought to create a bioluminescent reporter that dynamically and noninvasively measures ATM kinase activity in living cells and subjects. Methods and Materials: Using the split luciferase technology, we constructed a hybrid cDNA, ATM-reporter (ATMR), coding for a protein that quantitatively reports on changes in ATM kinase activity through changes in bioluminescence. Results: Treatment of ATMR-expressing cells with ATM inhibitors resulted in a dose-dependent increase in bioluminescence activity. In contrast, induction of ATM kinase activity upon irradiation resulted in a decrease in reporter activity that correlated with ATM and Chk2 activation by immunoblotting in a time-dependent fashion. Nuclear targeting improved ATMR sensitivity to both ATM inhibitors and radiation, whereas a mutant ATMR (lacking the target phosphorylation site) displayed a muted response. Treatment with ATM inhibitors and small interfering (si)RNA-targeted knockdown of ATM confirm the specificity of the reporter. Using reporter expressing xenografted tumors demonstrated the ability of ATMR to report in ATM activity in mouse models that correlated in a time-dependent fashion with changes in Chk2 activity. Conclusions: We describe the development and validation of a novel, specific, noninvasive bioluminescent reporter that enables monitoring of ATM activity in real time, in vitro and in vivo. Potential applications of this reporter include the identification and development of novel ATM inhibitors or ATM-interacting partners through high-throughput screens and in vivo pharmacokinetic/pharmacodynamic studies of ATM inhibitors in preclinical models.

  7. Segmentation of vascular structures and hematopoietic cells in 3D microscopy images and quantitative analysis

    Science.gov (United States)

    Mu, Jian; Yang, Lin; Kamocka, Malgorzata M.; Zollman, Amy L.; Carlesso, Nadia; Chen, Danny Z.

    2015-03-01

    In this paper, we present image processing methods for quantitative study of how the bone marrow microenvironment changes (characterized by altered vascular structure and hematopoietic cell distribution) caused by diseases or various factors. We develop algorithms that automatically segment vascular structures and hematopoietic cells in 3-D microscopy images, perform quantitative analysis of the properties of the segmented vascular structures and cells, and examine how such properties change. In processing images, we apply local thresholding to segment vessels, and add post-processing steps to deal with imaging artifacts. We propose an improved watershed algorithm that relies on both intensity and shape information and can separate multiple overlapping cells better than common watershed methods. We then quantitatively compute various features of the vascular structures and hematopoietic cells, such as the branches and sizes of vessels and the distribution of cells. In analyzing vascular properties, we provide algorithms for pruning fake vessel segments and branches based on vessel skeletons. Our algorithms can segment vascular structures and hematopoietic cells with good quality. We use our methods to quantitatively examine the changes in the bone marrow microenvironment caused by the deletion of Notch pathway. Our quantitative analysis reveals property changes in samples with deleted Notch pathway. Our tool is useful for biologists to quantitatively measure changes in the bone marrow microenvironment, for developing possible therapeutic strategies to help the bone marrow microenvironment recovery.

  8. Highly sensitive quantitative imaging for monitoring single cancer cell growth kinetics and drug response.

    Directory of Open Access Journals (Sweden)

    Mustafa Mir

    Full Text Available The detection and treatment of cancer has advanced significantly in the past several decades, with important improvements in our understanding of the fundamental molecular and genetic basis of the disease. Despite these advancements, drug-screening methodologies have remained essentially unchanged since the introduction of the in vitro human cell line screen in 1990. Although the existing methods provide information on the overall effects of compounds on cell viability, they are restricted by bulk measurements, large sample sizes, and lack capability to measure proliferation kinetics at the individual cell level. To truly understand the nature of cancer cell proliferation and to develop personalized adjuvant therapies, there is a need for new methodologies that provide quantitative information to monitor the effect of drugs on cell growth as well as morphological and phenotypic changes at the single cell level. Here we show that a quantitative phase imaging modality known as spatial light interference microscopy (SLIM addresses these needs and provides additional advantages over existing proliferation assays. We demonstrate these capabilities through measurements on the effects of the hormone estradiol and the antiestrogen ICI182,780 (Faslodex on the growth of MCF-7 breast cancer cells. Along with providing information on changes in the overall growth, SLIM provides additional biologically relevant information. For example, we find that exposure to estradiol results in rapidly growing cells with lower dry mass than the control population. Subsequently blocking the estrogen receptor with ICI results in slower growing cells, with lower dry masses than the control. This ability to measure changes in growth kinetics in response to environmental conditions provides new insight on growth regulation mechanisms. Our results establish the capabilities of SLIM as an advanced drug screening technology that provides information on changes in proliferation

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-15

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

  10. Quantitative imaging of protein targets in the human brain with PET

    Science.gov (United States)

    Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

    2015-11-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

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

    Science.gov (United States)

    Psilodimitrakopoulos, Sotiris; Amat-Roldan, Ivan; Loza-Alvarez, Pablo; Artigas, David

    2012-10-01

    Based on its polarization dependency, second harmonic generation (PSHG) microscopy has been proven capable to structurally characterize molecular architectures in different biological samples. By exploiting this polarization dependency of the SHG signal in every pixel of the image, average quantitative structural information can be retrieved in the form of PSHG image histograms. In the present study we experimentally show how the PSHG image histograms can be affected by the organization of the SHG active molecules. Our experimental scenario grounds on two inherent properties of starch granules. Firstly, we take advantage of the radial organization of amylopectin molecules (the SHG source in starch) to attribute shifts of the image histograms to the existence of tilted off the plane molecules. Secondly, we use the property of starch to organize upon hydration to demonstrate that the degree of structural order at the molecular level affects the width of the PSHG image histograms. The shorter the width is the more organized the molecules in the sample are, resulting in a reliable method to measure order. The implication of this finding is crucial to the interpretation of PSHG images used for example in tissue diagnostics.

  12. Advanced quantitative imaging of musculoskeletal disorders (Conference Presentation)

    Science.gov (United States)

    Chaudhary, Rajeev; Halanski, Matthew; Campagnola, Paul J.

    2017-03-01

    Previous studies have shown that bone growth acceleration can occur in many animal species after periosteal resection (removal of a strip of periosteum) with minimum morbidity. This has numerous clinical applications, including treatment of limb length differences. Here we use Second Harmonic Generation (SHG) imaging microscopy to evaluate changes in collagen architecture reflective of the different strains the periosteum may encounter during bone growth. Specifically, we image rabbit tibial periosteum strips at -20%, 0%, 5%, and 10% strains. We first quantify these changes using the SHG creation ratio (Forward/Backward) or the initially emitted SHG directionality to provide information on the fibril level of assembly. The in situ (i.e. physiological) strain had the highest creation ratio compared to the non-in situ strains of -20%, 5%, and 10%, which were shown to be significantly different via RCBD statistical analysis. These trends are consistent with SHG phasematching considerations, where more organized fibrils/fibers result in primarily forward emitted components, which here is the physiological strain. We further use the relative SHG conversion efficiency to assess the tissue structure under strain, where this results from the combination of collagen concentration and organization. The 0% strain SHG conversion efficiency was significantly higher than all other strains, where this is expected as the fibers have the highest local density and organization, and is consistent with the emission directionality results. Importantly, due to the underlying physical process, the label-free SHG imaging modality can non-invasively monitor the effect of treatments for bone growth and other orthopedic disorders.

  13. Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M.; Beck, R.N.

    1992-06-01

    This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

  14. Schlieren Imaging of Microthruster Exhausts for Qualitative and Quantitative Analysis

    OpenAIRE

    Lekholm, Ville; Palmer, Kristoffer; Thornell, Greger

    2012-01-01

    Abstract. Schlieren imaging is a method used to visualize differences in refractiveindex within a medium. It is a powerful and straightforward tool for sensitiveand high-resolution visualization of, e.g., gas flows. Here, heated cold gasmicrothrusters were studied with this technique. The thrusters are manufacturedusing microelectromechanical systems technology, and measure 22×22×0.85 mm. Thenozzles are approximately 20 µm wide at the throat, and 350 µm wide at the exit.Through these studies, v...

  15. Quantitative imaging of tumor vasculature using multispectral optoacoustic tomography (MSOT)

    Science.gov (United States)

    Tomaszewski, Michal R.; Quiros-Gonzalez, Isabel; Joseph, James; Bohndiek, Sarah E.

    2017-03-01

    The ability to evaluate tumor oxygenation in the clinic could indicate prognosis and enable treatment monitoring, since oxygen deficient cancer cells are often more resistant to chemotherapy and radiotherapy. MultiSpectral Optoacoustic Tomography (MSOT) is a hybrid technique combining the high contrast of optical imaging with spatial resolution and penetration depth similar to ultrasound. We hypothesized that MSOT could reveal both tumor vascular density and function based on modulation of blood oxygenation. We performed MSOT on nude mice (n=8) bearing subcutaneous xenograft PC3 tumors using an inVision 256 (iThera Medical). The mice were maintained under inhalation anesthesia during imaging and respired oxygen content was modified from 21% to 100% and back. After imaging, Hoechst 33348 was injected to indicate vascular perfusion and permeability. Tumors were then extracted for histopathological analysis and fluorescence microscopy. The acquired data was analyzed to extract a bulk measurement of blood oxygenation (SO2MSOT) from the whole tumor using different approaches. The tumors were also automatically segmented into 5 regions to investigate the effect of depth on SO2MSOT. Baseline SO2MSOT values at 21% and 100% oxygen breathing showed no relationship with ex vivo measures of vascular density or function, while the change in SO2MSOT showed a strong negative correlation to Hoechst intensity (r=- 0.92, p=0.0016). Tumor voxels responding to oxygen challenge were spatially heterogeneous. We observed a significant drop in SO2 MSOT value with tumor depth following a switch of respiratory gas from air to oxygen (0.323+/-0.017 vs. 0.11+/-0.05, p=0.009 between 0 and 1.5mm depth), but no such effect for air breathing (0.265+/-0.013 vs. 0.19+/-0.04, p=0.14 between 0 and 1.5mm depth). Our results indicate that in subcutaneous prostate tumors, baseline SO2MSOT levels do not correlate to tumor vascular density or function while the magnitude of the response to oxygen

  16. Molecular Imaging and Precision Medicine in Breast Cancer.

    Science.gov (United States)

    Chudgar, Amy V; Mankoff, David A

    2017-01-01

    Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Bishnu P. Joshi

    2010-06-01

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

  18. Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

    Science.gov (United States)

    Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

    2017-05-01

    Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

  19. Genetic algorithm based image binarization approach and its quantitative evaluation via pooling

    Science.gov (United States)

    Hu, Huijun; Liu, Ya; Liu, Maofu

    2015-12-01

    The binarized image is very critical to image visual feature extraction, especially shape feature, and the image binarization approaches have been attracted more attentions in the past decades. In this paper, the genetic algorithm is applied to optimizing the binarization threshold of the strip steel defect image. In order to evaluate our genetic algorithm based image binarization approach in terms of quantity, we propose the novel pooling based evaluation metric, motivated by information retrieval community, to avoid the lack of ground-truth binary image. Experimental results show that our genetic algorithm based binarization approach is effective and efficiency in the strip steel defect images and our quantitative evaluation metric on image binarization via pooling is also feasible and practical.

  20. Qualification of National Cancer Institute-Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials.

    Science.gov (United States)

    Scheuermann, Joshua S; Reddin, Janet S; Opanowski, Adam; Kinahan, Paul E; Siegel, Barry A; Shankar, Lalitha K; Karp, Joel S

    2017-07-01

    The National Cancer Institute developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to prequalify imaging facilities at all of the National Cancer Institute-designated comprehensive and clinical cancer centers for oncology trials using advanced imaging techniques, including PET. Here we review the CQIE PET/CT scanner qualification process and results in detail. Methods: Over a period of approximately 5 y, sites were requested to submit a variety of phantoms, including uniform and American College of Radiology-approved phantoms, PET/CT images, and examples of clinical images. Submissions were divided into 3 distinct time periods: initial submission (T0) and 2 requalification submissions (T1 and T2). Images were analyzed using standardized procedures, and scanners received a pass or fail designation. Sites had the opportunity to submit new data for scanners that failed. Quantitative results were compared across scanners within a given time period and across time periods for a given scanner. Results: Data from 65 unique PET/CT scanners across 56 sites were submitted for CQIE T0 qualification; 64 scanners passed the qualification. Data from 44 (68%) of those 65 scanners were submitted for T2. From T0 to T2, the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% for T1 to 67% for T2. The most common reasons for failure were SUV outside specifications, incomplete submission, and uniformity issues. Uniform phantom and American College of Radiology-approved phantom results between scanner manufacturers were similar. Conclusion: The results of the CQIE process showed that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, for quantitative imaging-based trials, further evaluation of the relationships between the level of

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  3. Quantitative contrast-enhanced MR imaging of the optic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.H. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Rubinstein, D. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Brown, M. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Yuh, W. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Birch-Iensen, M. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Szumowski, J. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Stears, J. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States)

    1994-11-01

    During the acute stages of optic neuritis damage to the blood-optic nerve barrier can be detected using i.v. paramagnetic contrast-enhanced MR imaging. Quantification of the enhancement pattern of the optic nerve, intraorbital fat and muscle was determined in 15 normal subjects using 3 fat-suppression MR imaging methods: T1-weighted spin-echo and spoiled gradient-echo sequences preceded by a flat-frequency selective pulse (FATSAT+SE and FATSAT+SPGR, respectively) and a pulse sequence combining CHOPPER fat suppression with a fat-frequency selective preparation pulse (HYBRID). Pre- and postcontrast-enhanced studies were acquired for FATSAT+SE and FATSAT+SPGR. There was no significant enhancement of the optic nerve by either method (mean increase of 0.96% and 5.3%, respectively), while there was significant enhancement in muscle (mean 118.2% and 108.2%, respectively; p<0.005) and fat (mean increase of 13% and 37%, respectively; p<0.05). Postcontrast optic nerve/muscle signal intensity ratios (mean, SD) were 0.51 (0.07), 0.58 (0.05) and 0.75 (0.05) for FATSAT+SE, FATSAT+SPGR and HYBRID, respectively. These results suggest a practical methodology and range of values for normal signal intensity increases and ratios of tissue signal that can be used as objective measures of optic neuritis for natural history studies and treatment trials. (orig.).

  4. Quantitative photothermal phase imaging of red blood cells using digital holographic photothermal microscope.

    Science.gov (United States)

    Vasudevan, Srivathsan; Chen, George C K; Lin, Zhiping; Ng, Beng Koon

    2015-05-10

    Photothermal microscopy (PTM), a noninvasive pump-probe high-resolution microscopy, has been applied as a bioimaging tool in many biomedical studies. PTM utilizes a conventional phase contrast microscope to obtain highly resolved photothermal images. However, phase information cannot be extracted from these photothermal images, as they are not quantitative. Moreover, the problem of halos inherent in conventional phase contrast microscopy needs to be tackled. Hence, a digital holographic photothermal microscopy technique is proposed as a solution to obtain quantitative phase images. The proposed technique is demonstrated by extracting phase values of red blood cells from their photothermal images. These phase values can potentially be used to determine the temperature distribution of the photothermal images, which is an important study in live cell monitoring applications.

  5. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  6. Dependence of quantitative accuracy of CT perfusion imaging on system parameters

    Science.gov (United States)

    Li, Ke; Chen, Guang-Hong

    2017-03-01

    Deconvolution is a popular method to calculate parametric perfusion parameters from four dimensional CT perfusion (CTP) source images. During the deconvolution process, the four dimensional space is squeezed into three-dimensional space by removing the temporal dimension, and a prior knowledge is often used to suppress noise associated with the process. These additional complexities confound the understanding about deconvolution-based CTP imaging system and how its quantitative accuracy depends on parameters and sub-operations involved in the image formation process. Meanwhile, there has been a strong clinical need in answering this question, as physicians often rely heavily on the quantitative values of perfusion parameters to make diagnostic decisions, particularly during an emergent clinical situation (e.g. diagnosis of acute ischemic stroke). The purpose of this work was to develop a theoretical framework that quantitatively relates the quantification accuracy of parametric perfusion parameters with CTP acquisition and post-processing parameters. This goal was achieved with the help of a cascaded systems analysis for deconvolution-based CTP imaging systems. Based on the cascaded systems analysis, the quantitative relationship between regularization strength, source image noise, arterial input function, and the quantification accuracy of perfusion parameters was established. The theory could potentially be used to guide developments of CTP imaging technology for better quantification accuracy and lower radiation dose.

  7. Molecular imaging of apoptosis: from micro to macro.

    Science.gov (United States)

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

    2015-01-01

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

  8. Molecular Imaging of Apoptosis: From Micro to Macro

    Science.gov (United States)

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

    2015-01-01

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

  9. The next few years: nuclear medicine and molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Eil, P.J. [Middlesex Hospital Mortimer Street, Institute of Nuclear Medicine, London (United Kingdom)

    2002-10-01

    Nuclear medicine in the future will be integrated in best practice in diagnosis, staging and re-staging of disease, treatment monitoring and indeed specific new therapy. Routine multi modality imaging has clearly arrived whilst some image fusion is still required. Intra and inter modality special registration is in progress. The impact of image fusion especially PET/CT on radiotherapy planning will be major. There are major developments in therapy and especially the treatment of lymphoma with new tracers such as yttrium-90 and iodine 131 labelled anti-CD monoclonal antibodies. New registered tracers are impacting. Cancer profiling will be improved with molecular phenotype with biopsy and imaging and organ staging via imaging technology. (N.C.)

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

    Science.gov (United States)

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

    2016-09-01

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

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

    NARCIS (Netherlands)

    Chen, Y.

    2012-01-01

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

  12. In vivo molecular and genomic imaging: new challenges for imaging physics.

    Science.gov (United States)

    Cherry, Simon R

    2004-02-07

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

  13. Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chen [Department of Ultrasound, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022 (China); Lee, Dong-Hoon; Zhang, Kai; Li, Wenxiao; Zhou, Jinyuan [Division of MR Research, Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287 (United States); Mangraviti, Antonella; Tyler, Betty [Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287 (United States); Su, Lin; Zhang, Yin; Zhang, Bin; Wong, John; Wang, Ken Kang-Hsin; Velarde, Esteban; Ding, Kai, E-mail: kding1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 (United States)

    2015-08-15

    Purpose: Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Methods: Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performed to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Results: Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T{sub 2}, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p < 0.05). The APTw signal was correlated with three CEUS parameters, rise time (r = − 0.527, p < 0.05), time to peak (r = − 0.501, p < 0.05), and perfusion index (r = 458, p < 0.05). Cerebral blood flow was correlated with rise time (r = − 0.589, p < 0.01) and time to peak (r = − 0.543, p < 0.05). Conclusions: MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.

  14. Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model.

    Science.gov (United States)

    Yang, Chen; Lee, Dong-Hoon; Mangraviti, Antonella; Su, Lin; Zhang, Kai; Zhang, Yin; Zhang, Bin; Li, Wenxiao; Tyler, Betty; Wong, John; Wang, Ken Kang-Hsin; Velarde, Esteban; Zhou, Jinyuan; Ding, Kai

    2015-08-01

    Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performed to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T2, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p correlated with three CEUS parameters, rise time (r = - 0.527, p correlated with rise time (r = - 0.589, p < 0.01) and time to peak (r = - 0.543, p < 0.05). MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.

  15. Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

    Science.gov (United States)

    Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

    2016-05-01

    A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.

  16. Perfluorocarbon nanoparticles for physiological and molecular imaging and therapy.

    Science.gov (United States)

    Chen, Junjie; Pan, Hua; Lanza, Gregory M; Wickline, Samuel A

    2013-11-01

    Herein, we review the use of non-nephrotoxic perfluorocarbon nanoparticles (PFC NPs) for noninvasive detection and therapy of kidney diseases, and we provide a synopsis of other related literature pertinent to their anticipated clinical application. Recent reports indicate that PFC NPs allow for quantitative mapping of kidney perfusion and oxygenation after ischemia-reperfusion injury with the use of a novel multinuclear (1)H/(19)F magnetic resonance imaging approach. Furthermore, when conjugated with targeting ligands, the functionalized PFC NPs offer unique and quantitative capabilities for imaging inflammation in the kidney of atherosclerotic ApoE-null mice. In addition, PFC NPs can facilitate drug delivery for treatment of inflammation, thrombosis, and angiogenesis in selected conditions that are comorbidities for kidney failure. The excellent safety profile of PFC NPs with respect to kidney injury positions these nanomedicine approaches as promising diagnostic and therapeutic candidates for treating and following acute and chronic kidney diseases.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  19. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Quong, J N

    2004-02-19

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

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

    Science.gov (United States)

    Ciccarelli, Olga; Barkhof, Frederik; Bodini, Benedetta; De Stefano, Nicola; Golay, Xavier; Nicolay, Klaas; Pelletier, Daniel; Pouwels, Petra J W; Smith, Seth A; Wheeler-Kingshott, Claudia A M; Stankoff, Bruno; Yousry, Tarek; Miller, David H

    2014-08-01

    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.

  1. Imaging and Quantitation Techniques for Tracking Cargo along Endosome-to-Golgi Transport Pathways

    Directory of Open Access Journals (Sweden)

    Paul A. Gleeson

    2013-02-01

    Full Text Available Recent improvements in the resolution of light microscopy, coupled with the development of a range of fluorescent-based probes, have provided new approaches to dissecting membrane domains and the regulation of membrane trafficking. Here, we review these advances, as well as highlight developments in quantitative image analysis and novel unbiased analytical approaches to quantitate protein localization. The application of these approaches to endosomal sorting and endosome-to-Golgi transport is discussed.

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

    Science.gov (United States)

    Sallam, Karim; Wu, Joseph C

    2010-01-01

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

  3. Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

    Science.gov (United States)

    Clementi, Massimo; Bagnarelli, Patrizia

    2015-10-01

    In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

  4. Quantitative assessment of renal function with magnetic resonance imaging; Quantitative Erfassung der renalen Funktion mit der Magnetresonanztomographie

    Energy Technology Data Exchange (ETDEWEB)

    Schoenberg, S.O.; Bock, M.; Aumann, S.; Essig, M.; Floemer, F.; Knopp, M.V.; Kaick, G. van [Deutsches Krebsforschungszentrum Heidelberg (Germany). Abt. Radiologische Diagnostik und Therapie; Just, A. [Heidelberg Univ. (Germany). 1. Physiologisches Inst.

    2000-10-01

    Aim. To show the potential of various methods in magnetic resonance imaging for the evaluation of renal function. Material and Methods. A combined assessment of renal morphology, renal hemodynamics and function is proposed. Various techniques are explained, including multiphasic 3D gadolinium MR angiography, MR phase-contrast flow measurements, quantitative perfusion measurements with intravascular contrast agents, and MR renography and MR urography. The use of these techniques is demonstrated for renovascular diseases. Results. The combined use of these techniques allows renal artery stenosis to be accurately detected and evaluation of renal blood flow, perfusion, glomerular filtration rate, and renal excretion. Based on true quantitative parameters, the hemodynamic and functional significance of the stenosis can be assessed. Renovascular diseases can be differentiated from renoparenchymal disease. Conclusion. For the assessment of renal function, functional magnetic resonance imaging techniques are an important alternative to nuclear medicine. The predictive value regarding the effect of revascularization is currently under investigation. (orig.) [German] Fragestellung. Verschiedene Methoden der Magnetresonanztomographie zur quantitativen Erfassung der Nierenfunktion sollen aufgezeigt werden. Methodik. Es werden MR-Techniken zur kombinierten Beurteilung der renalen Morphologie, Haemodynamik und Funktion der Niere vorgestellt. Zur Anwendung kommen hierbei die multiphasische 3-D-Gadolinium-MR-Angiographie, die MR-Phasenkontrastflussmessung, die quantitative Perfusionsmessung mit intravasalen Kontrastmitteln sowie die MR-Renographie/MR-Urographie. Die Methoden werden exemplarisch am Beispiel renovaskulaerer Erkrankungen demonstriert. Ergebnisse. Mit den vorgestellten Methoden lassen sich Nierenarterienstenosen akkurat detektieren sowie Aenderungen des renalen Blutflusses, der Nierenperfusion, der Filtrationsleistung sowie der renalen Ausscheidung erfassen. Auf der

  5. Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization

    OpenAIRE

    Mattijs Elschot; Johannes Franciscus Wilhelmus Nijsen; Alida Johanna Dam; Hugo Wilhelmus Antonius Maria de Jong

    2011-01-01

    BACKGROUND: Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compa...

  6. Microscopy imaging and quantitative phase contrast mapping in turbid microfluidic channels by digital holography.

    Science.gov (United States)

    Paturzo, Melania; Finizio, Andrea; Memmolo, Pasquale; Puglisi, Roberto; Balduzzi, Donatella; Galli, Andrea; Ferraro, Pietro

    2012-09-07

    We show that sharp imaging and quantitative phase-contrast microcopy is possible in microfluidics in flowing turbid media by digital holography. In fact, in flowing liquids with suspended colloidal particles, clear vision is hindered and cannot be recovered by any other microscopic imaging technique. On the contrary, using digital holography, clear imaging is possible thanks to the Doppler frequency shift experienced by the photons scattered by the flowing colloidal particles, which do not contribute to the interference process, i.e. the recorded hologram. The method is illustrated and imaging results are demonstrated for pure phase objects, i.e. biological cells in microfluidic channels.

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

    DEFF Research Database (Denmark)

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

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

  8. “易损斑块无创、高分辨超声功能与分子定量成像”研究2010年度报告%Noninvasive and High Resolution Ultrasound Functional and Molecular Quantitative Imaging of VAulnerable Plaque 2010 Annual Report

    Institute of Scientific and Technical Information of China (English)

    万明习; 宗瑜瑾; 万锦锦; 吴道澄; 谷晓林

    2016-01-01

    This year we make important progresses in following aspects: (1) Principle and methods of high resolution ultrasound imaging.(2)Preparation of microbubbles, ultrasound perfusion imaging with high CTR and perfusion parameter imaging.(3) motion and elasticity imaging of vascular and surrounding tissue.(4)mechanism of ultrasound cavition. The high frame rate and higher frequency ultrasound images have been made IBP super-resolution reconstruction based on optic flow and super-resolution reconstruction based on grey scale ununiformity correction, and the axial and lateral resolution after reconstruction can reach to four times higher than the original images. Additionally, ultrasound contrast imaging with high CTR, perfusion parameter quantitative imaging and pulse inverse wavelet transform contrast imaging have been realized on low cost digital ultrasound imaging system. Preliminary optical experimental results of sonoluminesence (SL) and sonochemoluminesence (SCL) in focused ultrasound free cavitation field have been obtained in a pH similar to human physiological environment.%该研究本年度在高分辨超声成像理论与方法、微泡制备、高CTR造影成像及灌注参量成像、血管及其周围组织运动与弹性检测成像、超声空化机理等4个方面研究取得重要进展。对高帧率、较高频率超声图像分别进行了基于光流场(OF)的IBP超分辨重建和基于灰度非均匀校正的超分辨重建,重建后轴向及横向分辨率可达到原始图像的4倍以上;并在低成本数字超声成像系统上实现了高CTR值的造影成像和灌注参量定量成像和脉冲逆转小波变换造影成像技术;初步得到模仿人体生理pH环境下,聚焦超声自由空化场中声致发光(SL)的光学检测实验结果及声致化学发光(SCL)的光学检测实验结果。

  9. Quantitative Characterization of Super-Resolution Infrared Imaging Based on Time-Varying Focal Plane Coding

    Science.gov (United States)

    Wang, X.; Yuan, Y.; Zhang, J.; Chen, Y.; Cheng, Y.

    2014-10-01

    High resolution infrared image has been the goal of an infrared imaging system. In this paper, a super-resolution infrared imaging method using time-varying coded mask is proposed based on focal plane coding and compressed sensing theory. The basic idea of this method is to set a coded mask on the focal plane of the optical system, and the same scene could be sampled many times repeatedly by using time-varying control coding strategy, the super-resolution image is further reconstructed by sparse optimization algorithm. The results of simulation are quantitatively evaluated by introducing the Peak Signal-to-Noise Ratio (PSNR) and Modulation Transfer Function (MTF), which illustrate that the effect of compressed measurement coefficient r and coded mask resolution m on the reconstructed image quality. Research results show that the proposed method will promote infrared imaging quality effectively, which will be helpful for the practical design of new type of high resolution ! infrared imaging systems.

  10. High resolution quantitative phase imaging of live cells with constrained optimization approach

    Science.gov (United States)

    Pandiyan, Vimal Prabhu; Khare, Kedar; John, Renu

    2016-03-01

    Quantitative phase imaging (QPI) aims at studying weakly scattering and absorbing biological specimens with subwavelength accuracy without any external staining mechanisms. Use of a reference beam at an angle is one of the necessary criteria for recording of high resolution holograms in most of the interferometric methods used for quantitative phase imaging. The spatial separation of the dc and twin images is decided by the reference beam angle and Fourier-filtered reconstructed image will have a very poor resolution if hologram is recorded below a minimum reference angle condition. However, it is always inconvenient to have a large reference beam angle while performing high resolution microscopy of live cells and biological specimens with nanometric features. In this paper, we treat reconstruction of digital holographic microscopy images as a constrained optimization problem with smoothness constraint in order to recover only complex object field in hologram plane even with overlapping dc and twin image terms. We solve this optimization problem by gradient descent approach iteratively and the smoothness constraint is implemented by spatial averaging with appropriate size. This approach will give excellent high resolution image recovery compared to Fourier filtering while keeping a very small reference angle. We demonstrate this approach on digital holographic microscopy of live cells by recovering the quantitative phase of live cells from a hologram recorded with nearly zero reference angle.

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

    Science.gov (United States)

    Qin, Zhengtao

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

  12. Imprints of Molecular Clouds in Radio Continuum Images

    CERN Document Server

    Yusef-Zadeh, F

    2012-01-01

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

  13. Quantitative assessment of p-glycoprotein expression and function using confocal image analysis.

    Science.gov (United States)

    Hamrang, Zahra; Arthanari, Yamini; Clarke, David; Pluen, Alain

    2014-10-01

    P-glycoprotein is implicated in clinical drug resistance; thus, rapid quantitative analysis of its expression and activity is of paramout importance to the design and success of novel therapeutics. The scope for the application of quantitative imaging and image analysis tools in this field is reported here at "proof of concept" level. P-glycoprotein expression was utilized as a model for quantitative immunofluorescence and subsequent spatial intensity distribution analysis (SpIDA). Following expression studies, p-glycoprotein inhibition as a function of verapamil concentration was assessed in two cell lines using live cell imaging of intracellular Calcein retention and a routine monolayer fluorescence assay. Intercellular and sub-cellular distributions in the expression of the p-glycoprotein transporter between parent and MDR1-transfected Madin-Derby Canine Kidney cell lines were examined. We have demonstrated that quantitative imaging can provide dose-response parameters while permitting direct microscopic analysis of intracellular fluorophore distributions in live and fixed samples. Analysis with SpIDA offers the ability to detect heterogeniety in the distribution of labeled species, and in conjunction with live cell imaging and immunofluorescence staining may be applied to the determination of pharmacological parameters or analysis of biopsies providing a rapid prognostic tool.

  14. Rapid and Quantitative Assessment of Cancer Treatment Response Using In Vivo Bioluminescence Imaging

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla

    2000-01-01

    Full Text Available Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies [1 ]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal [2], subcutaneous, and intravascular [3] cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeuticinduced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI, respectively. There was excellent correlation (r=0.91 between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951. These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.

  15. Objective evaluation of reconstruction methods for quantitative SPECT imaging in the absence of ground truth

    Science.gov (United States)

    Jha, Abhinav K.; Song, Na; Caffo, Brian; Frey, Eric C.

    2015-03-01

    Quantitative single-photon emission computed tomography (SPECT) imaging is emerging as an important tool in clinical studies and biomedical research. There is thus a need for optimization and evaluation of systems and algorithms that are being developed for quantitative SPECT imaging. An appropriate objective method to evaluate these systems is by comparing their performance in the end task that is required in quantitative SPECT imaging, such as estimating the mean activity concentration in a volume of interest (VOI) in a patient image. This objective evaluation can be performed if the true value of the estimated parameter is known, i.e. we have a gold standard. However, very rarely is this gold standard known in human studies. Thus, no-gold-standard techniques to optimize and evaluate systems and algorithms in the absence of gold standard are required. In this work, we developed a no-gold-standard technique to objectively evaluate reconstruction methods used in quantitative SPECT when the parameter to be estimated is the mean activity concentration in a VOI. We studied the performance of the technique with realistic simulated image data generated from an object database consisting of five phantom anatomies with all possible combinations of five sets of organ uptakes, where each anatomy consisted of eight different organ VOIs. Results indicate that the method pro- vided accurate ranking of the reconstruction methods. We also demonstrated the application of consistency checks to test the no-gold-standard output.

  16. Quantitative analysis of biological tissues using Fourier transform-second-harmonic generation imaging

    Science.gov (United States)

    Ambekar Ramachandra Rao, Raghu; Mehta, Monal R.; Toussaint, Kimani C., Jr.

    2010-02-01

    We demonstrate the use of Fourier transform-second-harmonic generation (FT-SHG) imaging of collagen fibers as a means of performing quantitative analysis of obtained images of selected spatial regions in porcine trachea, ear, and cornea. Two quantitative markers, preferred orientation and maximum spatial frequency are proposed for differentiating structural information between various spatial regions of interest in the specimens. The ear shows consistent maximum spatial frequency and orientation as also observed in its real-space image. However, there are observable changes in the orientation and minimum feature size of fibers in the trachea indicating a more random organization. Finally, the analysis is applied to a 3D image stack of the cornea. It is shown that the standard deviation of the orientation is sensitive to the randomness in fiber orientation. Regions with variations in the maximum spatial frequency, but with relatively constant orientation, suggest that maximum spatial frequency is useful as an independent quantitative marker. We emphasize that FT-SHG is a simple, yet powerful, tool for extracting information from images that is not obvious in real space. This technique can be used as a quantitative biomarker to assess the structure of collagen fibers that may change due to damage from disease or physical injury.

  17. Engineering imaging probes and molecular machines for nanomedicine.

    Science.gov (United States)

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

    2012-10-01

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

  18. Quantitative imaging of basic functions in renal (patho)physiology.

    Science.gov (United States)

    Kang, Jung Julie; Toma, Ildiko; Sipos, Arnold; McCulloch, Fiona; Peti-Peterdi, Janos

    2006-08-01

    Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased approximately 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times ( approximately 45 s) to glomerular filtration, with a delay of approximately 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.

  19. Quantitative method to assess caries via fluorescence imaging from the perspective of autofluorescence spectral analysis

    Science.gov (United States)

    Chen, Q. G.; Zhu, H. H.; Xu, Y.; Lin, B.; Chen, H.

    2015-08-01

    A quantitative method to discriminate caries lesions for a fluorescence imaging system is proposed in this paper. The autofluorescence spectral investigation of 39 teeth samples classified by the International Caries Detection and Assessment System levels was performed at 405 nm excitation. The major differences in the different caries lesions focused on the relative spectral intensity range of 565-750 nm. The spectral parameter, defined as the ratio of wavebands at 565-750 nm to the whole spectral range, was calculated. The image component ratio R/(G + B) of color components was statistically computed by considering the spectral parameters (e.g. autofluorescence, optical filter, and spectral sensitivity) in our fluorescence color imaging system. Results showed that the spectral parameter and image component ratio presented a linear relation. Therefore, the image component ratio was graded as 1.62 to quantitatively classify sound, early decay, established decay, and severe decay tissues, respectively. Finally, the fluorescence images of caries were experimentally obtained, and the corresponding image component ratio distribution was compared with the classification result. A method to determine the numerical grades of caries using a fluorescence imaging system was proposed. This method can be applied to similar imaging systems.

  20. Cold Spring Harbor symposia on quantitative biology: Volume L, Molecular biology of development

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    This volume contains contributions by contributors to the 1985 Cold Springs Harbor Symposium on Quantitative Biology. This year's theme was Molecular Biology of Development. The volume consists of 104 articles organized by content into sections entitled Nuclear/Cytoplasmic Interactions in Early Development; Lineage and Segmentation/Pattern Formation; Homeotic Mutants; Homeo Boxes; Tissue Specificity/Position Effects; Expression of Genes Introduced into Transgenic Mice; Induced Developmental Defects; Control of Gene Expression; Sex Determination; Cell-cycle Effects; Pluripotent Cells/Oncogenes; Cellular Differentiation; and Developmental Neurobiology.

  1. Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

    Science.gov (United States)

    Rinehart, Matthew; Grab, Sheila; Rohan, Lisa; Katz, David; Wax, Adam

    2014-01-01

    We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

  2. Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

    Directory of Open Access Journals (Sweden)

    Matthew Rinehart

    Full Text Available We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

  3. Quantitative degenerate four-wave mixing spectroscopy: Probes for molecular species

    Energy Technology Data Exchange (ETDEWEB)

    Farrow, R.; Rakestraw, D.; Paul, P.; Lucht, R.; Danehy, P.; Friedman-Hill, E.; Germann, G. [Sandia National Laboratories, Livermore, CA (United States)

    1993-12-01

    Resonant degenerate four-wave mixing (DFWM) is currently the subject of intensive investigation as a sensitive diagnostic tool for molecular species. DFWM has the advantage of generating a coherent (beam-like) signal which results in null-background detection and provides excellent immunity to background-light interference. Since multiple one-photon resonances are involved in the signal generation process, the DFWM technique can allow sensitive detection of molecules via electronic, vibrational or rotational transitions. These properties combine to make DFWM a widely applicable diagnostic technique for the probing of molecular species. The authors are conducting fundamental and applied investigations of DFWM for quantitative measurements of trace species in reacting gases. During the past year, efforts have been focussed in two areas: (1) understanding the effects of collisional processes on the DFWM signal generation process, and (2) exploring the applicability of infrared DFWM to detect polyatomic molecules via rovibrational transitions.

  4. Molecular Structural Characterization and Quantitative Prediction of Reduced Ion Mobility Constants for Diversified Organic Compounds

    Institute of Scientific and Technical Information of China (English)

    HE Liu; LIANG Gui-Zhao; LI Zhi-Liang

    2008-01-01

    Based on two-dimensional topological structures, a novel molecular electronega- tivity interaction vector with hybridization (MEHIV) was developed to describe atomic hybri- dization state in different molecular environments. Five quantitative models by MEHIV cha- racterization and multiple linear regression modeling were successfully established to predict reduced ion mobility constants (K0) of alkanes, aromatic hydrocarbons, fatty alcohols, fatty aldehydes and ketones and carboxylic esters. The correlation coefficients Rcv by leave-one-out cross-validation are 0.792, 0.787, 0.949, 0.972 and 0.981, respectively, and the standard deviations SDcv are 0.067, 0.086, 0.064, 0.043 and 0.042, respectively. These results suggested that MEHIV is an excellent topological index descriptor with many advantages such as straightforward physicochemical meaning, high characterization competence, convenient expan- sibility and easy manipulation.

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

    Science.gov (United States)

    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.

  6. Ultrafast Molecular Imaging by Laser Induced Electron Diffraction

    CERN Document Server

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

    2010-01-01

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

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

    OpenAIRE

    Hawkins, DM; Trache, A; Ellis, EA; Stevenson, D.; Holzenburg, A.; Meininger, GA; Reddy, Subrayal M

    2006-01-01

    We have employed FITC-albumin as the protein template molecule in an aqueous phase molecular imprinted polymer (HydroMIP) strategy. For the first time, the use of a fluorescently labelled template is reported, with subsequent characterisation of the smart material to show that the HydroMIP possess a significant molecular memory in comparison to that of the nonimprinted control polymer (HydroNIP). The imaging of the FITC-albumin imprinted HydroMIP using confocal microscopy is described, with t...

  8. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    DEFF Research Database (Denmark)

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten

    2013-01-01

    Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE).......Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE)....

  9. Analysis of Vaginal Microbicide Film Hydration Kinetics by Quantitative Imaging Refractometry

    OpenAIRE

    Matthew Rinehart; Sheila Grab; Lisa Rohan; David Katz; Adam Wax

    2014-01-01

    We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interf...

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

    Science.gov (United States)

    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.

  11. New Imaging Frontiers in Cardiology: Fast and Quantitative Maps from Raw Data.

    Science.gov (United States)

    Santarelli, Maria Filomena; Vanello, Nicola; Scipioni, Michele; Valvano, Giuseppe; Landini, Luigi

    2017-03-28

    Among the novelties in the field of cardiovascular imaging, the construction of quantitative maps in a fast and efficient way is one of the most interesting aspects of the clinical research. Quantitative parametric maps are typically obtained by post processing dynamic images, that is, sets of images usually acquired in different temporal intervals, where several images with different contrasts are obtained. Magnetic resonance (MR) imaging, and emission tomography (positron emission and single photon emission) are the imaging techniques best suited for the formation of quantitative maps. In this review article we present several methods that can be used for obtaining parametric maps, in a fast way, starting from the acquired raw data. We describe both methods commonly used in clinical research, and more innovative methods that build maps directly from the raw data, without going through the image reconstruction. We briefly described recently developed methods in magnetic resonance (MR) imaging that accelerate further the MR raw data generation, based on appropriate sub-sampling of k-space; then, we described recently developed methods for generating MR parametric maps. With regard to the emission tomography techniques, we gave an overview of both conventional methods, and more recently developed direct estimation algorithms for parametric image reconstruction from dynamic positron emission tomography data. We have provided an overview of the possible approaches that can be followed to realize useful parametric maps from imaging raw data. We moved from the conventional approaches to more recent and efficient methods for accelerating the raw data generation and the of parametric maps formation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Imaging molecular shapes with molecular-frame photoelectron angular distributions from core hole ionization

    Science.gov (United States)

    Trevisan, C. S.; McCurdy, C. W.; Rescigno, T. N.

    2012-10-01

    We demonstrate, for a class of molecules containing a single heavy atom, the striking result that molecular-frame photoelectron angular distributions resulting from core-level ionization can be used to obtain three-dimensional images of the target molecule at low photoelectron energies. We demonstrate this finding with the results of theoretical calculations on methane, ammonia and water.

  13. Quantitative interpretation of the transition voltages in gold-poly(phenylene) thiol-gold molecular junctions

    KAUST Repository

    Wu, Kunlin

    2013-01-01

    The transition voltage of three different asymmetric Au/poly(phenylene) thiol/Au molecular junctions in which the central molecule is either benzene thiol, biphenyl thiol, or terphenyl thiol is investigated by first-principles quantum transport simulations. For all the junctions, the calculated transition voltage at positive polarity is in quantitative agreement with the experimental values and shows weak dependence on alterations of the Au-phenyl contact. When compared to the strong coupling at the Au-S contact, which dominates the alignment of various molecular orbitals with respect to the electrode Fermi level, the coupling at the Au-phenyl contact produces only a weak perturbation. Therefore, variations of the Au-phenyl contact can only have a minor influence on the transition voltage. These findings not only provide an explanation to the uniformity in the transition voltages found for π-conjugated molecules measured with different experimental methods, but also demonstrate the advantage of transition voltage spectroscopy as a tool for determining the positions of molecular levels in molecular devices. © 2013 AIP Publishing LLC.

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

    Science.gov (United States)

    Abou, D S; Pickett, J E; Thorek, D L J

    2015-10-01

    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.

  15. Two worlds collide: image analysis methods for quantifying structural variation in cluster molecular dynamics.

    Science.gov (United States)

    Steenbergen, K G; Gaston, N

    2014-02-14

    Inspired by methods of remote sensing image analysis, we analyze structural variation in cluster molecular dynamics (MD) simulations through a unique application of the principal component analysis (PCA) and Pearson Correlation Coefficient (PCC). The PCA analysis characterizes the geometric shape of the cluster structure at each time step, yielding a detailed and quantitative measure of structural stability and variation at finite temperature. Our PCC analysis captures bond structure variation in MD, which can be used to both supplement the PCA analysis as well as compare bond patterns between different cluster sizes. Relying only on atomic position data, without requirement for a priori structural input, PCA and PCC can be used to analyze both classical and ab initio MD simulations for any cluster composition or electronic configuration. Taken together, these statistical tools represent powerful new techniques for quantitative structural characterization and isomer identification in cluster MD.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Dynamical image-charge effect in molecular tunnel junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun; Thygesen, Kristian Sommer

    2014-01-01

    When an electron tunnels between two metal contacts it temporarily induces an image charge (IC) in the electrodes which acts back on the tunneling electron. It is usually assumed that the IC forms instantaneously such that a static model for the image potential applies. Here we investigate how th...... that the dynamical corrections can reduce the conductance by more than a factor of two when compared to static GW or density functional theory where the molecular energy levels have been shifted to match the exact quasiparticle levels....

  18. Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

    Science.gov (United States)

    Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

    2015-06-15

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients.

  19. Breast Cancer Detection by B7-H3 Targeted Ultrasound Molecular Imaging

    Science.gov (United States)

    Bachawal, Sunitha V.; Jensen, Kristin C.; Wilson, Katheryne E.; Tian, Lu; Lutz, Amelie M.; Willmann, Jürgen K.

    2015-01-01

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T cell co-regulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor and malignant breast pathologies for diagnostic purposes. Through an immunohistochemical analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. PMID:25899053

  20. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

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

  1. Quantitative imaging of glutathione in live cells using a reversible reaction-based ratiometric fluorescent probe

    Science.gov (United States)

    Glutathione (GSH) plays an important role in maintaining redox homeostasis inside cells. Currently, there are no methods available to quantitatively assess the GSH concentration in live cells. Live cell fluorescence imaging revolutionized the understanding of cell biology and has become an indispens...

  2. A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry.

    NARCIS (Netherlands)

    Ellis, S.R.; Bruinen, A.L.; Heeren, R.M.A.|info:eu-repo/dai/nl/105188476

    2014-01-01

    Mass spectrometry imaging (MSI) has evolved into a valuable tool across many fields of chemistry, biology, and medicine. However, arguably its greatest disadvantage is the difficulty in acquiring quantitative data regarding the surface concentration of the analyte(s) of interest. These difficulties

  3. Quantitative planar Raman imaging through a spectrograph: visualisation of a supersonic wedge flow

    NARCIS (Netherlands)

    Tolboom, R.A.L.; Dam, N.J.; Meulen, J.J. ter; Bakker, P.G.

    2005-01-01

    Planar Raman imaging through a spectrograph is demonstrated as a diagnostic tool for quantitative flow visualisation of internal supersonic wedge flow. A dedicated Bayesian deconvolution filter is used to remove the spectral structure that is introduced by the spectrograph. The 2D density field is d

  4. Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy : Magnetic resonance imaging versus echocardiography

    NARCIS (Netherlands)

    Posma, JL; Blanksma, PK; vanderWall, EE; Hamer, HPM; Mooyaart, EL; Lie, KI

    1996-01-01

    To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle hypert

  5. FURTHER EVALUATION OF QUANTITATIVE NUCLEAR IMAGE FEATURES FOR CLASSIFICATION OF LUNG CARCINOMAS

    NARCIS (Netherlands)

    THUNNISSEN, FBJM; DIEGENBACH, PC; VANHATTUM, AH; TOLBOOM, J; VANDERSLUIS, DM; SCHAAFSMA, W; HOUTHOFF, HJ; BAAK, JPA

    1992-01-01

    The usefulness of quantitative nuclear image features (QNI) for the histological classification of lung carcinomas was investigated. As no clear distinction could be established between the distributions of these features for the nuclei of squamous cell, adenocarcinoma, and large cell carcinoma, the

  6. Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy : Magnetic resonance imaging versus echocardiography

    NARCIS (Netherlands)

    Posma, JL; Blanksma, PK; vanderWall, EE; Hamer, HPM; Mooyaart, EL; Lie, KI

    1996-01-01

    To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle hypert

  7. A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry.

    NARCIS (Netherlands)

    Ellis, S.R.; Bruinen, A.L.; Heeren, R.M.A.

    2014-01-01

    Mass spectrometry imaging (MSI) has evolved into a valuable tool across many fields of chemistry, biology, and medicine. However, arguably its greatest disadvantage is the difficulty in acquiring quantitative data regarding the surface concentration of the analyte(s) of interest. These difficulties

  8. PET quantitation and imaging of the non-pure positron-emitting iodine isotope 124I.

    Science.gov (United States)

    Herzog, H; Tellman, L; Qaim, S M; Spellerberg, S; Schmid, A; Coenen, H H

    2002-05-01

    A series of PET studies using phantoms is presented to characterize the imaging and quantitative performance of the positron-emitting iodine isotope 124I. Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction was applied for the gamma-rays emitted together with the positrons. As compared to 18F, in studies with 124I there is a small loss of image resolution and contrast, and an increase in background. The quantitative results varied between different scanners and various acquisition as well as reconstruction modes, with an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that quantitation of a radiopharmaceutical labelled with 124I is feasible and may be improved by the development of specific corrections.

  9. Spectro-refractometry of individual microscopic objects using swept-source quantitative phase imaging.

    Science.gov (United States)

    Jung, Jae-Hwang; Jang, Jaeduck; Park, Yongkeun

    2013-11-05

    We present a novel spectroscopic quantitative phase imaging technique with a wavelength swept-source, referred to as swept-source diffraction phase microscopy (ssDPM), for quantifying the optical dispersion of microscopic individual samples. Employing the swept-source and the principle of common-path interferometry, ssDPM measures the multispectral full-field quantitative phase imaging and spectroscopic microrefractometry of transparent microscopic samples in the visible spectrum with a wavelength range of 450-750 nm and a spectral resolution of less than 8 nm. With unprecedented precision and sensitivity, we demonstrate the quantitative spectroscopic microrefractometry of individual polystyrene beads, 30% bovine serum albumin solution, and healthy human red blood cells.

  10. [Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies]. DOE annual report, 1994--95

    Energy Technology Data Exchange (ETDEWEB)

    DeNardo, S.J.

    1995-12-31

    The authors describe results which have not yet been published from their associated studies listed in the title. For the first, they discuss Lym-1 single chain genetically engineered molecules, analysis of molecular genetic coded messages to enhance tumor response, and human dosimetry and therapeutic human use radiopharmaceuticals. Studies in phantoms includes a discussion of planar image quantitation, counts coincidence correction, organ studies, tumor studies, and {sup 90}Y quantitation with Bremsstrahlung imaging. The study on SPECT discusses attenuation correction and scatter correction. Preclinical studies investigated uptake of {sup 90}Y-BrE-3 in mice using autoradiography. Clinical studies discuss image quantitation verses counts from biopsy samples, S factors for radiation dose calculation, {sup 67}Cu imaging studies for lymphoma cancer, and {sup 111}In MoAb imaging studies for breast cancer to predict {sup 90}Y MoAb therapy.

  11. [Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies]. DOE annual report, 1994--95

    Energy Technology Data Exchange (ETDEWEB)

    DeNardo, S.J.

    1995-12-31

    The authors describe results which have not yet been published from their associated studies listed in the title. For the first, they discuss Lym-1 single chain genetically engineered molecules, analysis of molecular genetic coded messages to enhance tumor response, and human dosimetry and therapeutic human use radiopharmaceuticals. Studies in phantoms includes a discussion of planar image quantitation, counts coincidence correction, organ studies, tumor studies, and {sup 90}Y quantitation with Bremsstrahlung imaging. The study on SPECT discusses attenuation correction and scatter correction. Preclinical studies investigated uptake of {sup 90}Y-BrE-3 in mice using autoradiography. Clinical studies discuss image quantitation verses counts from biopsy samples, S factors for radiation dose calculation, {sup 67}Cu imaging studies for lymphoma cancer, and {sup 111}In MoAb imaging studies for breast cancer to predict {sup 90}Y MoAb therapy.

  12. Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency.

    Science.gov (United States)

    Asselta, Rosanna; Platè, Manuela; Robusto, Michela; Borhany, Munira; Guella, Ilaria; Soldà, Giulia; Afrasiabi, Abdolreza; Menegatti, Marzia; Shamsi, Tahir; Peyvandi, Flora; Duga, Stefano

    2015-03-01

    Fibrinogen is a plasma glycoprotein mainly synthesised by hepatocytes and circulating as a 340-kDa hexamer consisting of two sets of three different polypeptide chains (Aα, Bβ, and γ, encoded by the FGA, FGB, and FGG gene, respectively). Congenital afibrinogenaemia and hypofibrinogenaemia are rare bleeding disorders characterised by abnormally low levels of functional and immunoreactive fibrinogen in plasma, associated with haemorrhagic manifestations of variable severity. While afibrinogenaemia is caused by mutations in the homozygous or compound heterozygous state in one of the three fibrinogen genes, hypofibrinogenaemia is generally due to heterozygous mutations, and is usually characterised by a milder phenotype. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination codons, and missense mutations often affecting fibrinogen assembly and/or secretion. Here we report the clinical and molecular characterisation of 13 unrelated afibrinogenaemic and eight hypofibrinogenaemic patients, leading to the identification of 17 different mutations (10 hitherto unknown). All the newly-identified missense and splicing mutations werein vitro expressed to verify their pathogenic role. Our data increase the number of mutations causing quantitative fibrinogen deficiencies by about 7 %. The high number of private mutations identified in the analysed probands indicates that the full mutational screening of the three fibrinogen genes is still required for molecular diagnosis.

  13. Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma using Quantitative Image Analysis.

    Science.gov (United States)

    Zheng, Jian; Chakraborty, Jayasree; Chapman, William C; Gerst, Scott; Gonen, Mithat; Pak, Linda M; Jarnagin, William R; DeMatteo, Ronald P; Do, Richard Kg; Simpson, Amber L; Allen, Peter J; Balachandran, Vinod P; D'Angelica, Michael I; Kingham, T Peter; Vachharajani, Neeta

    2017-09-20

    Microvascular invasion (MVI) is a significant risk factor for early recurrence after resection or transplantation for hepatocellular carcinoma (HCC). Knowledge of MVI status would help guide treatment recommendations but is generally identified after surgery. This study aims to predict MVI preoperatively using quantitative image analysis. From 2 institutions, 120 patients submitted to resection of HCC from 2003 to 2015 were included. The largest tumor from preoperative CT was subjected to quantitative image analysis, which uses an automated computer algorithm to capture regional variation in CT enhancement patterns. Quantitative imaging features by automatic analysis, qualitative radiographic descriptors by 2 radiologists, and preoperative clinical variables were included in multivariate analysis to predict histologic MVI. Histologic MVI was identified in 19 (37%) patients with tumors ≤ 5 cm and 34 (49%) patients with tumors > 5 cm. Among patients with ≤ 5 cm tumors, none of clinical findings or radiographic descriptors was associated with MVI; however, quantitative feature based on angle co-occurrence matrix predicted MVI with area under curve (AUC) 0.80, positive predictive value (PPV) 63% and negative predictive value (NPV) 85%. In patients with > 5 cm tumors, higher α-fetoprotein (AFP) level, larger tumor size, and viral hepatitis history were associated with MVI, whereas radiographic descriptors did not. However, a multivariate model combining AFP, tumor size, hepatitis status, and quantitative feature based on local binary pattern predicted MVI with AUC 0.88, PPV 72% and NPV 96%. This study reveals the potential importance of quantitative image analysis as a predictor of MVI. Copyright © 2017. Published by Elsevier Inc.

  14. Molecular indexing enables quantitative targeted RNA sequencing and reveals poor efficiencies in standard library preparations.

    Science.gov (United States)

    Fu, Glenn K; Xu, Weihong; Wilhelmy, Julie; Mindrinos, Michael N; Davis, Ronald W; Xiao, Wenzhong; Fodor, Stephen P A

    2014-02-01

    We present a simple molecular indexing method for quantitative targeted RNA sequencing, in which mRNAs of interest are selectively captured from complex cDNA libraries and sequenced to determine their absolute concentrations. cDNA fragments are individually labeled so that each molecule can be tracked from the original sample through the library preparation and sequencing process. Multiple copies of cDNA fragments of identical sequence become distinct through labeling, and replicate clones created during PCR amplification steps can be identified and assigned to their distinct parent molecules. Selective capture enables efficient use of sequencing for deep sampling and for the absolute quantitation of rare or transient transcripts that would otherwise escape detection by standard sequencing methods. We have also constructed a set of synthetic barcoded RNA molecules, which can be introduced as controls into the sample preparation mix and used to monitor the efficiency of library construction. The quantitative targeted sequencing revealed extremely low efficiency in standard library preparations, which were further confirmed by using synthetic barcoded RNA molecules. This finding shows that standard library preparation methods result in the loss of rare transcripts and highlights the need for monitoring library efficiency and for developing more efficient sample preparation methods.

  15. Quantitative annular dark-field imaging of single-layer graphene-II: atomic-resolution image contrast.

    Science.gov (United States)

    Yamashita, Shunsuke; Koshiya, Shogo; Nagai, Takuro; Kikkawa, Jun; Ishizuka, Kazuo; Kimoto, Koji

    2015-12-01

    We have investigated how accurately atomic-resolution annular dark-field (ADF) images match between experiments and simulations to conduct more reliable crystal structure analyses. Quantitative ADF imaging, in which the ADF intensity at each pixel represents the fraction of the incident probe current, allows us to perform direct comparisons with simulations without the use of fitting parameters. Although the conventional comparison suffers from experimental uncertainties such as an amorphous surface layer and specimen thickness, in this study we eliminated such uncertainties by using a single-layer graphene as a specimen. Furthermore, to reduce image distortion and shot noises in experimental images, multiple acquisitions with drift correction were performed, and the atomic ADF contrast was quantitatively acquired. To reproduce the experimental ADF contrast, we used three distribution functions as the effective source distribution in simulations. The optimum distribution function and its full-width at half-maximum were evaluated by measuring the residuals between the experimental and simulated images. It was found that the experimental images could be explained well by a linear combination of a Gaussian function and a Lorentzian function with a longer tail than the Gaussian function.

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

    Science.gov (United States)

    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.

  17. Quantitative comparisons of radar image, scatterometer, and surface roughness data from Pisgah Crater, CA

    Science.gov (United States)

    Farr, T. G.; Engheta, N.

    1983-01-01

    The relationships between radar image brightness and backscatter coefficient, between the backscatter coefficient and surface roughness, and between surface roughness and geology, must be established in order to satisfy criteria for the quantitative use of radar images. Attention is presently given to the merits of calibrated radar images and scatterometers as sources of the backscatter coefficient, theories that yield the coefficient on the basis of known surface roughness (and vice versa), and the geologic interpretation of surface roughness and backscatter signatures. These considerations are discussed in the case of the Pisgah Crater and lava field in the Mojave Desert of California.

  18. Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C.-C. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China); Hwang, Jeng-Jong [Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)]. E-mail: jjhwang@ym.edu.tw; Ting, G. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China); Tseng, Y.-L. [Taiwan Liposome Company, Taipei 115, Taiwan (China); Wang, S.-J. [Department of Nuclear Medicine, Veterans General Hospital, Taipei 112, Taiwan (China); Whang-Peng, J. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China)

    2007-02-01

    In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating tumor growth. In this study, the kinetic of tumor growth has been assessed in C26 colon carcinoma bearing BALB/c mouse model. The ability of BLI to noninvasively quantitate the growth of subcutaneous tumors transplanted with C26 cells genetically engineered to stably express firefly luciferase and herpes simplex virus type-1 thymidine kinase (C26/tk-luc). A good correlation (R {sup 2}=0.998) of photon emission to the cell number was found in vitro. Tumor burden and tumor volume were monitored in vivo over time by quantitation of photon emission using Xenogen IVIS 50 and standard external caliper measurement, respectively. At various time intervals, tumor-bearing mice were imaged to determine the correlation of in vivo BLI to tumor volume. However, a correlation of BLI to tumor volume was observed when tumor volume was smaller than 1000 mm{sup 3} (R {sup 2}=0.907). {gamma} Scintigraphy combined with [{sup 131}I]FIAU was another imaging modality used for verifying the previous results. In conclusion, this study showed that bioluminescence imaging is a powerful and quantitative tool for the direct assay to monitor tumor growth in vivo. The dual reporter genes transfected tumor-bearing animal model can be applied in the evaluation of the efficacy of new developed anti-cancer drugs.

  19. A method for improved clustering and classification of microscopy images using quantitative co-localization coefficients

    LENUS (Irish Health Repository)

    Singan, Vasanth R

    2012-06-08

    AbstractBackgroundThe localization of proteins to specific subcellular structures in eukaryotic cells provides important information with respect to their function. Fluorescence microscopy approaches to determine localization distribution have proved to be an essential tool in the characterization of unknown proteins, and are now particularly pertinent as a result of the wide availability of fluorescently-tagged constructs and antibodies. However, there are currently very few image analysis options able to effectively discriminate proteins with apparently similar distributions in cells, despite this information being important for protein characterization.FindingsWe have developed a novel method for combining two existing image analysis approaches, which results in highly efficient and accurate discrimination of proteins with seemingly similar distributions. We have combined image texture-based analysis with quantitative co-localization coefficients, a method that has traditionally only been used to study the spatial overlap between two populations of molecules. Here we describe and present a novel application for quantitative co-localization, as applied to the study of Rab family small GTP binding proteins localizing to the endomembrane system of cultured cells.ConclusionsWe show how quantitative co-localization can be used alongside texture feature analysis, resulting in improved clustering of microscopy images. The use of co-localization as an additional clustering parameter is non-biased and highly applicable to high-throughput image data sets.

  20. Delayed 18F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Thomassen, Anders; Takx, Richard A P

    2014-01-01

    BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can...... potentially improve quantitation of vascular inflammation. METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries...... and thoracic aorta by calculating the blood-pool corrected maximum standardized uptake value (cSUVMAX). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 90 and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between c...

  1. Quantitative magnetic resonance imaging of the fetal brain in utero: Methods and applications

    Institute of Scientific and Technical Information of China (English)

    Anat; Biegon; Chen; Hoffmann

    2014-01-01

    Application of modern magnetic resonance imaging(MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and accepted ultrasonographic approach are the subject of a continuing debate; however the focus of this review is on the even younger field of quantitative MRI as applied to non-invasive studies of fetal brain development. The techniques covered under this header include structural MRI when followed by quan-titative(e.g., volumetric) analysis, as well as quantita-tive analyses of diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. The majority of the published work re-viewed here reflects information gathered from normal fetuses scanned during the 3rd trimester, with relatively smaller number of studies of pathological samples including common congenital pathologies such as ven-triculomegaly and viral infection.

  2. Quantitative Analysis of Micro-CT Imaging and Histopathological Signatures of Experimental Arthritis in Rats

    Directory of Open Access Journals (Sweden)

    Matthew D. Silva

    2004-10-01

    Full Text Available Micro-computed tomographic (micro-CT imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA, quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10 stored in formalin consisted of approximately 600 30-μm slices acquired on a 512 × 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%. The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.

  3. Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain.

    Science.gov (United States)

    Liu, Chunlei; Li, Wei; Tong, Karen A; Yeom, Kristen W; Kuzminski, Samuel

    2015-07-01

    Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging.

  4. Computational Challenges and Collaborative Projects in the NCI Quantitative Imaging Network.

    Science.gov (United States)

    Farahani, Keyvan; Kalpathy-Cramer, Jayashree; Chenevert, Thomas L; Rubin, Daniel L; Sunderland, John J; Nordstrom, Robert J; Buatti, John; Hylton, Nola

    2016-12-01

    The Quantitative Imaging Network (QIN) of the National Cancer Institute (NCI) conducts research in development and validation of imaging tools and methods for predicting and evaluating clinical response to cancer therapy. Members of the network are involved in examining various imaging and image assessment parameters through network-wide cooperative projects. To more effectively use the cooperative power of the network in conducting computational challenges in benchmarking of tools and methods and collaborative projects in analytical assessment of imaging technologies, the QIN Challenge Task Force has developed policies and procedures to enhance the value of these activities by developing guidelines and leveraging NCI resources to help their administration and manage dissemination of results. Challenges and Collaborative Projects (CCPs) are further divided into technical and clinical CCPs. As the first NCI network to engage in CCPs, we anticipate a variety of CCPs to be conducted by QIN teams in the coming years. These will be aimed to benchmark advanced software tools for clinical decision support, explore new imaging biomarkers for therapeutic assessment, and establish consensus on a range of methods and protocols in support of the use of quantitative imaging to predict and assess response to cancer therapy.

  5. Advancing Molecular Therapies through In Vivo Bioluminescent Imaging

    Directory of Open Access Journals (Sweden)

    Anton McCaffrey

    2003-04-01

    Full Text Available Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLI is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.

  6. PET-based molecular nuclear neuro-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

    2004-04-01

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

  7. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arif Sheikh

    2017-02-01

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

  8. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    Science.gov (United States)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  9. A custom-built PET phantom design for quantitative imaging of printed distributions

    Energy Technology Data Exchange (ETDEWEB)

    Markiewicz, P J; Angelis, G I; Kotasidis, F; Green, M; Matthews, J C [School of Cancer and Enabling Sciences, MAHSC, University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Lionheart, W R [School of Mathematics, Alan Turing Building, The University of Manchester (United Kingdom); Reader, A J, E-mail: p.markiewicz@manchester.ac.uk [Montreal Neurological Institute, McGill University, Montreal (Canada)

    2011-11-07

    This note presents a practical approach to a custom-made design of PET phantoms enabling the use of digital radioactive distributions with high quantitative accuracy and spatial resolution. The phantom design allows planar sources of any radioactivity distribution to be imaged in transaxial and axial (sagittal or coronal) planes. Although the design presented here is specially adapted to the high-resolution research tomograph (HRRT), the presented methods can be adapted to almost any PET scanner. Although the presented phantom design has many advantages, a number of practical issues had to be overcome such as positioning of the printed source, calibration, uniformity and reproducibility of printing. A well counter (WC) was used in the calibration procedure to find the nonlinear relationship between digital voxel intensities and the actual measured radioactive concentrations. Repeated printing together with WC measurements and computed radiography (CR) using phosphor imaging plates (IP) were used to evaluate the reproducibility and uniformity of such printing. Results show satisfactory printing uniformity and reproducibility; however, calibration is dependent on the printing mode and the physical state of the cartridge. As a demonstration of the utility of using printed phantoms, the image resolution and quantitative accuracy of reconstructed HRRT images are assessed. There is very good quantitative agreement in the calibration procedure between HRRT, CR and WC measurements. However, the high resolution of CR and its quantitative accuracy supported by WC measurements made it possible to show the degraded resolution of HRRT brain images caused by the partial-volume effect and the limits of iterative image reconstruction. (note)

  10. Quantitative Ultrasound Spectroscopic Imaging for Characterization of Disease Extent in Prostate Cancer Patients1

    Science.gov (United States)

    Sadeghi-Naini, Ali; Sofroni, Ervis; Papanicolau, Naum; Falou, Omar; Sugar, Linda; Morton, Gerard; Yaffe, Martin J.; Nam, Robert; Sadeghian, Alireza; Kolios, Michael C.; Chung, Hans T.; Czarnota, Gregory J.

    2015-01-01

    Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was investigated clinically for the noninvasive detection and extent characterization of disease in cancer patients and compared to whole-mount, whole-gland histopathology of radical prostatectomy specimens. Fifteen patients with prostate cancer underwent a volumetric transrectal ultrasound scan before radical prostatectomy. Conventional-frequency (~ 5 MHz) ultrasound images and radiofrequency data were collected from patients. Normalized power spectra were used as the basis of quantitative ultrasound spectroscopy. Specifically, color-coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were computed and used to characterize prostate tissue in ultrasound images. Areas of cancer were identified in whole-mount histopathology specimens, and disease extent was correlated to that estimated from quantitative ultrasound parametric images. Midband fit and 0-MHz intercept parameters were found to be best associated with the presence of disease as located on histopathology whole-mount sections. Obtained results indicated a correlation between disease extent estimated noninvasively based on midband fit parametric images and that identified histopathologically on prostatectomy specimens, with an r2 value of 0.71 (P < .0001). The 0-MHz intercept parameter demonstrated a lower level of correlation with histopathology. Spectral slope parametric maps offered no discrimination of disease. Multiple regression analysis produced a hybrid disease characterization model (r2 = 0.764, P < .05), implying that the midband fit biomarker had the greatest correlation with the histopathologic extent of disease. This work demonstrates that quantitative ultrasound spectroscopic imaging can be used for detecting prostate cancer and characterizing disease extent noninvasively, with corresponding gross three-dimensional histopathologic correlation. PMID:25749174

  11. Quantitative Ultrasound Spectroscopic Imaging for Characterization of Disease Extent in Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ali Sadeghi-Naini

    2015-02-01

    Full Text Available Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was investigated clinically for the noninvasive detection and extent characterization of disease in cancer patients and compared to whole-mount, whole-gland histopathology of radical prostatectomy specimens. Fifteen patients with prostate cancer underwent a volumetric transrectal ultrasound scan before radical prostatectomy. Conventional-frequency (~5 MHz ultrasound images and radiofrequency data were collected from patients. Normalized power spectra were used as the basis of quantitative ultrasound spectroscopy. Specifically, color-coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were computed and used to characterize prostate tissue in ultrasound images. Areas of cancer were identified in whole-mount histopathology specimens, and disease extent was correlated to that estimated from quantitative ultrasound parametric images. Midband fit and 0-MHz intercept parameters were found to be best associated with the presence of disease as located on histopathology whole-mount sections. Obtained results indicated a correlation between disease extent estimated noninvasively based on midband fit parametric images and that identified histopathologically on prostatectomy specimens, with an r2 value of 0.71 (P < .0001. The 0-MHz intercept parameter demonstrated a lower level of correlation with histopathology. Spectral slope parametric maps offered no discrimination of disease. Multiple regression analysis produced a hybrid disease characterization model (r2 = 0.764, P < .05, implying that the midband fit biomarker had the greatest correlation with the histopathologic extent of disease. This work demonstrates that quantitative ultrasound spectroscopic imaging can be used for detecting prostate cancer and characterizing disease extent noninvasively, with corresponding gross three-dimensional histopathologic correlation.

  12. Quantitative ultrasound spectroscopic imaging for characterization of disease extent in prostate cancer patients.

    Science.gov (United States)

    Sadeghi-Naini, Ali; Sofroni, Ervis; Papanicolau, Naum; Falou, Omar; Sugar, Linda; Morton, Gerard; Yaffe, Martin J; Nam, Robert; Sadeghian, Alireza; Kolios, Michael C; Chung, Hans T; Czarnota, Gregory J

    2015-02-01

    Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was investigated clinically for the noninvasive detection and extent characterization of disease in cancer patients and compared to whole-mount, whole-gland histopathology of radical prostatectomy specimens. Fifteen patients with prostate cancer underwent a volumetric transrectal ultrasound scan before radical prostatectomy. Conventional-frequency (~5MHz) ultrasound images and radiofrequency data were collected from patients. Normalized power spectra were used as the basis of quantitative ultrasound spectroscopy. Specifically, color-coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were computed and used to characterize prostate tissue in ultrasound images. Areas of cancer were identified in whole-mount histopathology specimens, and disease extent was correlated to that estimated from quantitative ultrasound parametric images. Midband fit and 0-MHz intercept parameters were found to be best associated with the presence of disease as located on histopathology whole-mount sections. Obtained results indicated a correlation between disease extent estimated noninvasively based on midband fit parametric images and that identified histopathologically on prostatectomy specimens, with an r(2) value of 0.71 (P<.0001). The 0-MHz intercept parameter demonstrated a lower level of correlation with histopathology. Spectral slope parametric maps offered no discrimination of disease. Multiple regression analysis produced a hybrid disease characterization model (r(2)=0.764, P<.05), implying that the midband fit biomarker had the greatest correlation with the histopathologic extent of disease. This work demonstrates that quantitative ultrasound spectroscopic imaging can be used for detecting prostate cancer and characterizing disease extent noninvasively, with corresponding gross three-dimensional histopathologic correlation. Copyright © 2014 Neoplasia Press, Inc. Published by

  13. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

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    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  14. Review of imaging solutions for integrated quantitative immunohistochemistry in the Pathology daily practice.

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    Marcial GarcĂ­a Rojo

    2010-02-01

    Full Text Available Immunohistochemistry (IHC plays an essential role in Pathology. In order to improve reproducibility and standardization of the results interpretation, IHC quantification methods have been developed. IHC interpretation based in whole slide imaging or virtual microscopy is of special interest. The objective of this work is to review the different computer-based programs for automatic immunohistochemistry and Fluorescence In Situ Hybridization (FISH evaluation. Scanning solutions and image analysis software in immunohistochemistry were studied, focusing especially on systems based in virtual slides. Integrated scanning and image analysis systems are available (Bacus TMAScore, Dako ACIS III, Genetix Ariol, Aperio Image Analysis, 3DHistech Mirax HistoQuant, Bioimagene Pathiam. Other image analysis software systems (Definiens TissueMap, SlidePath Tissue Image Analysis can be applied to several virtual slide formats. Fluorescence is the preferred approach in HistoRx AQUA, since it allows for a better compartmentalization of signals. Multispectral imaging using CRi Nuance allows multiple antibodies immunohistochemistry, and different stain unmixing. Most current popular automated image analysis solutions are aimed to brightfield immunohistochemistry, but fluorescence and FISH solutions may become more important in the near future. Automated quantitative tissue microarrays (TMA analysis is essential to provide high-throughput analysis. Medical informatics standards in images (DICOM and workflow (IHE under development will foster the use of image analysis in Pathology Departments.

  15. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.

    Science.gov (United States)

    Meini, María-Rocío; Tomatis, Pablo E; Weinreich, Daniel M; Vila, Alejandro J

    2015-07-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters.

  16. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features

    Science.gov (United States)

    Meini, María-Rocío; Tomatis, Pablo E.; Weinreich, Daniel M.; Vila, Alejandro J.

    2015-01-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters. PMID:25767204

  17. Quantitative organization of GABAergic synapses in the molecular layer of the mouse cerebellar cortex.

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    Federica Briatore

    Full Text Available In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor alpha1 subunit (GABAARalpha1 was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the alpha1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using alpha-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex.

  18. Super-Resolution Molecular and Functional imaging of Nanoscale Architectures in Life and Materials Science

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    Satoshi eHabuchi

    2014-06-01

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

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

    KAUST Repository</