Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

DEFF Research Database (Denmark)

Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan

2012-01-01

of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were...... obtained. This study shows that the UV imaging methodology has considerable potential for characterizing transport properties in hydrogels, including monitoring the real-time spatial concentration distribution in vitro after administration by injection....

Targeting the treatment of drug abuse with molecular imaging

International Nuclear Information System (INIS)

Schiffer, Wynne K.; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L.

2007-01-01

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

Targeting the treatment of drug abuse with molecular imaging

Energy Technology Data Exchange (ETDEWEB)

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

2007-10-15

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

Image-guided drug delivery: preclinical applications and clinical translation

NARCIS (Netherlands)

Ojha, Tarun; Rizzo, Larissa; Storm, Gerrit; Kiessling, Fabian; Lammers, Twan Gerardus Gertudis Maria

2015-01-01

Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy.

Photoacoustic microscopy imaging for microneedle drug delivery

Science.gov (United States)

Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

2018-02-01

The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.

Science.gov (United States)

Vinegoni, Claudio; Fumene Feruglio, Paolo; Brand, Christian; Lee, Sungon; Nibbs, Antoinette E; Stapleton, Shawn; Shah, Sunil; Gryczynski, Ignacy; Reiner, Thomas; Mazitschek, Ralph; Weissleder, Ralph

2017-07-01

The ability to directly image and quantify drug-target engagement and drug distribution with subcellular resolution in live cells and whole organisms is a prerequisite to establishing accurate models of the kinetics and dynamics of drug action. Such methods would thus have far-reaching applications in drug development and molecular pharmacology. We recently presented one such technique based on fluorescence anisotropy, a spectroscopic method based on polarization light analysis and capable of measuring the binding interaction between molecules. Our technique allows the direct characterization of target engagement of fluorescently labeled drugs, using fluorophores with a fluorescence lifetime larger than the rotational correlation of the bound complex. Here we describe an optimized protocol for simultaneous dual-channel two-photon fluorescence anisotropy microscopy acquisition to perform drug-target measurements. We also provide the necessary software to implement stream processing to visualize images and to calculate quantitative parameters. The assembly and characterization part of the protocol can be implemented in 1 d. Sample preparation, characterization and imaging of drug binding can be completed in 2 d. Although currently adapted to an Olympus FV1000MPE microscope, the protocol can be extended to other commercial or custom-built microscopes.

Fluorescence optical imaging in anticancer drug delivery.

Science.gov (United States)

Etrych, Tomáš; Lucas, Henrike; Janoušková, Olga; Chytil, Petr; Mueller, Thomas; Mäder, Karsten

2016-03-28

In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. Copyright © 2016 Elsevier B.V. All rights reserved.

Has molecular imaging delivered to drug development?

Science.gov (United States)

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

2017-10-01

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

Your brain on drugs: imaging of drug-related changes in the central nervous system.

Science.gov (United States)

Tamrazi, Benita; Almast, Jeevak

2012-01-01

Drug abuse is a substantial problem in society today and is associated with significant morbidity and mortality. Various drugs are associated with serious complications affecting the brain, and it is critical to recognize the imaging findings of these complications to provide prompt medical management. The central nervous system (CNS) is a target organ for drugs of abuse as well as specific prescribed medications. Drugs of abuse affecting the CNS include cocaine, heroin, alcohol, amphetamines, toluene, and cannabis. Prescribed medications or medical therapies that can affect the CNS include immunosuppressants, antiepileptics, nitrous oxide, and total parenteral nutrition. The CNS complications of these drugs include neurovascular complications, encephalopathy, atrophy, infection, changes in the corpus callosum, and other miscellaneous changes. Imaging abnormalities indicative of these complications can be appreciated at both magnetic resonance (MR) imaging and computed tomography (CT). It is critical for radiologists to recognize complications related to drugs of abuse as well as iatrogenic effects of various medications. Therefore, diagnostic imaging modalities such as MR imaging and CT can play a pivotal role in the recognition and timely management of drug-related complications in the CNS.

Distribution of red blood cell antigens in drug-resistant and drug ...

African Journals Online (AJOL)

sofo

Frequency distribution of ABO, Rh-Hr, MN, Kell blood group system antigens were studied in 277 TB patients (151-drug-sensitive and 126 drug-resistant) of pulmonary tuberculosis to know whether there was any association between them, and also between drug resistance and sensitiveness. They were compared with 485 ...

Near-infrared imaging spectroscopy for counterfeit drug detection

Science.gov (United States)

Arnold, Thomas; De Biasio, Martin; Leitner, Raimund

2011-06-01

Pharmaceutical counterfeiting is a significant issue in the healthcare community as well as for the pharmaceutical industry worldwide. The use of counterfeit medicines can result in treatment failure or even death. A rapid screening technique such as near infrared (NIR) spectroscopy could aid in the search for and identification of counterfeit drugs. This work presents a comparison of two laboratory NIR imaging systems and the chemometric analysis of the acquired spectroscopic image data. The first imaging system utilizes a NIR liquid crystal tuneable filter and is designed for the investigation of stationary objects. The second imaging system utilizes a NIR imaging spectrograph and is designed for the fast analysis of moving objects on a conveyor belt. Several drugs in form of tablets and capsules were analyzed. Spectral unmixing techniques were applied to the mixed reflectance spectra to identify constituent parts of the investigated drugs. The results show that NIR spectroscopic imaging can be used for contact-less detection and identification of a variety of counterfeit drugs.

The role of radio pharmacological imaging in streamlining the drug development process

International Nuclear Information System (INIS)

Campbell, D. B.

1997-01-01

Radio imaging techniques have found a place in clinical diagnosis, but there has been a hesitancy to use this approach in drug development. This reluctance may have been due to the availability of ligands, the time and cost of synthesis and the number of centres and for many the benefits are not evident. The use in drug development is potentially large since tomography can measure drug levels, specific binding, blood flow and activity within the human body. In drug discovery, the synthesis of candidate drugs with specific binding properties are dependent on understanding the disease and using appropriate in vitro or animal models. Using small animal tomographs, these can be validated using radio imaging. Pharmacokinetics and metabolic problems, such as the distribution of inhaled gases, drug targeting into tumours of the brain or specific gastrointestinal absorption sites can be investigated within the human rather than relying on animals. The high specific activity allows low doses to be administered to man with limited safety studies permitting kinetic and metabolic studies to be undertaken early in development. Safety studies and ensuing toxicological endpoints in animals rely on histopathology for gross degenerative in physiological function. Where concern exists, radio imaging could detect early in situ changes in humans, for example hepatic toxicity, before they become hazardous. In clinical studies, the action of drugs can be measured directly at the effector site prior to undertaking longer studies, which is important for many diseases, but particularly for those such as Alzheimer's disease, where improvements may be slow or subtle

Fast analysis of narcotic drugs by optical chemical imaging

International Nuclear Information System (INIS)

Fisher, Michal; Bulatov, Vallery; Schechter, Israel

2003-01-01

A new technique is proposed for fast detection, identification and imaging of narcotic drugs in their solid phase. This technique, which requires only a tiny sample of a few microns, is based on microscopic chemical imaging. Minor sample preparation is required, and results are obtained within seconds. As far as we know, this is the most sensitive detection system available today for solid drugs. The technique can be applied for fast analysis of minute drug residues, and therefore is of considerable importance for forensic applications. It is shown that identification of drug traces in realistic matrixes is possible. Two main methods were applied in this study for detection of drugs and drug derivatives. The first method was based on direct detection and chemical imaging of the auto-fluorescence of the analyzed drugs. This method is applicable when the analyzed drug emits fluorescence under the experiment conditions, such as lysergic acid diethylamide (known as LSD). The second method was used for obtaining chemical imaging of drugs that do not fluoresce under the experiment conditions. In these cases fluorescent labeling dyes were applied to the examined samples (including the drug and the matrix). Both methods are simple and rapid, and require minor or no sample preparation at all. Detection limits are very low in the picogram range

Technologies for image distribution in hospitals

International Nuclear Information System (INIS)

Kotter, Elmar; Baumann, Tobias; Jaeger, Dieter; Langer, Mathias

2006-01-01

After the establishment of web-based image distribution, three challenges for image distribution can be identified today. Firstly, PACS (picture archiving and communication system) and the distribution of radiological images and reports need to be integrated with the emerging electronic medical record. Secondly, report and image data should be available on mobile devices like PDAs (personal digital assistants) or smartphones in the future. Thirdly, future systems must be available not only to transmit sectional images, but also to allow access to three- and four-dimensional data that are produced by multidetector CT and modern MR scanners. (orig.)

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The Administrator...

Image exploitation and dissemination prototype of distributed image processing

International Nuclear Information System (INIS)

Batool, N.; Huqqani, A.A.; Mahmood, A.

2003-05-01

Image processing applications requirements can be best met by using the distributed environment. This report presents to draw inferences by utilizing the existed LAN resources under the distributed computing environment using Java and web technology for extensive processing to make it truly system independent. Although the environment has been tested using image processing applications, its design and architecture is truly general and modular so that it can be used for other applications as well, which require distributed processing. Images originating from server are fed to the workers along with the desired operations to be performed on them. The Server distributes the task among the Workers who carry out the required operations and send back the results. This application has been implemented using the Remote Method Invocation (RMl) feature of Java. Java RMI allows an object running in one Java Virtual Machine (JVM) to invoke methods on another JVM thus providing remote communication between programs written in the Java programming language. RMI can therefore be used to develop distributed applications [1]. We undertook this project to gain a better understanding of distributed systems concepts and its uses for resource hungry jobs. The image processing application is developed under this environment

Distributed MIMO-ISAR Sub-image Fusion Method

Directory of Open Access Journals (Sweden)

Gu Wenkun

2017-02-01

Full Text Available The fast fluctuation associated with maneuvering a target’s radar cross-section often affects the imaging performance stability of traditional monostatic Inverse Synthetic Aperture Radar (ISAR. To address this problem, in this study, we propose an imaging method based on the fusion of sub-images of frequencydiversity-distributed multiple Input-Multiple Output-Inverse Synthetic Aperture Radar (MIMO-ISAR. First, we establish the analytic expression of a two-dimensional ISAR sub-image acquired by different channels of distributed MIMO-ISAR. Then, we derive the distance and azimuth distortion factors of the image acquired by the different channels. By compensating for the distortion of the ISAR image, we ultimately realize distributed MIMO-ISAR fusion imaging. Simulations verify the validity of this imaging method using distributed MIMO-ISAR.

A Development of Hybrid Drug Information System Using Image Recognition

Directory of Open Access Journals (Sweden)

HwaMin Lee

2015-04-01

Full Text Available In order to prevent drug abuse or misuse cases and avoid over-prescriptions, it is necessary for medicine taker to be provided with detailed information about the medicine. In this paper, we propose a drug information system and develop an application to provide information through drug image recognition using a smartphone. We designed a contents-based drug image search algorithm using the color, shape and imprint of drug. Our convenient application can provide users with detailed information about drugs and prevent drug misuse.

78 FR 734 - Medical Imaging Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-01-04

...] Medical Imaging Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS... and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Medical Imaging Drugs Advisory Committee. General Function of the Committee: To provide advice and recommendations...

Quality control of the paracetamol drug by chemometrics and imaging spectroscopy in the near infrared region

Science.gov (United States)

Baptistao, Mariana; Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

2011-09-01

In this work, it was used imaging spectroscopy and chemometric tools for the development and analysis of paracetamol and excipients in pharmaceutical formulations. It was also built concentration maps to study the distribution of the drug in the tablets surface. Multivariate models based on PLS regression were developed for paracetamol and excipients concentrations prediction. For the construction of the models it was used 31 samples in the tablet form containing the active principle in a concentration range of 30.0-90.0% (w/w) and errors below to 5% were obtained for validation samples. Finally, the study of the distribution in the drug was performed through the distribution maps of concentration of active principle and excipients. The analysis of maps showed the complementarity between the active principle and excipients in the tablets. The region with a high concentration of a constituent must have, necessarily, absence or low concentration of the other one. Thus, an alternative method for the paracetamol drug quality monitoring is presented.

78 FR 12762 - Joint Meeting of the Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory...

Science.gov (United States)

2013-02-25

...] Joint Meeting of the Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory Committee... be open to the public. Name of Committees: Medical Imaging Drugs Advisory Committee and the Oncologic... Special Medical Programs. [FR Doc. 2013-04141 Filed 2-22-13; 8:45 am] BILLING CODE 4160-01-P ...

76 FR 45402 - Advisory Committee; Medical Imaging Drugs Advisory Committee; Re-Establishment

Science.gov (United States)

2011-07-29

.... FDA-2010-N-0002] Advisory Committee; Medical Imaging Drugs Advisory Committee; Re- Establishment... (FDA) is announcing the re- establishment of the Medical Imaging Drugs Advisory Committee in FDA's Center for Drug Evaluation and Research. This rule amends the current language for the Medical Imaging...

Balanced distributed coding of omnidirectional images

Science.gov (United States)

Thirumalai, Vijayaraghavan; Tosic, Ivana; Frossard, Pascal

2008-01-01

This paper presents a distributed coding scheme for the representation of 3D scenes captured by stereo omni-directional cameras. We consider a scenario where images captured from two different viewpoints are encoded independently, with a balanced rate distribution among the different cameras. The distributed coding is built on multiresolution representation and partitioning of the visual information in each camera. The encoder transmits one partition after entropy coding, as well as the syndrome bits resulting from the channel encoding of the other partition. The decoder exploits the intra-view correlation and attempts to reconstruct the source image by combination of the entropy-coded partition and the syndrome information. At the same time, it exploits the inter-view correlation using motion estimation between images from different cameras. Experiments demonstrate that the distributed coding solution performs better than a scheme where images are handled independently, and that the coding rate stays balanced between encoders.

Image authentication using distributed source coding.

Science.gov (United States)

Lin, Yao-Chung; Varodayan, David; Girod, Bernd

2012-01-01

We present a novel approach using distributed source coding for image authentication. The key idea is to provide a Slepian-Wolf encoded quantized image projection as authentication data. This version can be correctly decoded with the help of an authentic image as side information. Distributed source coding provides the desired robustness against legitimate variations while detecting illegitimate modification. The decoder incorporating expectation maximization algorithms can authenticate images which have undergone contrast, brightness, and affine warping adjustments. Our authentication system also offers tampering localization by using the sum-product algorithm.

Inner ear barriers to nanomedicine-augmented drug delivery and imaging

Directory of Open Access Journals (Sweden)

Jing Zou

2016-12-01

Full Text Available There are several challenges to inner ear drug delivery and imaging due to the existence of tight biological barriers to the target structure and the dense bone surrounding it. Advances in imaging and nanomedicine may provide knowledge for overcoming the existing limitations to both the diagnosis and treatment of inner ear diseases. Novel techniques have improved the efficacy of drug delivery and targeting to the inner ear, as well as the quality and accuracy of imaging this structure. In this review, we will describe the pathways and biological barriers of the inner ear regarding drug delivery, the beneficial applications and limitations of the imaging techniques available for inner ear research, the behavior of engineered nanomaterials in inner ear applications, and future perspectives for nanomedicine-based inner ear imaging.

Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

Science.gov (United States)

Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

2013-07-01

Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging.

Science.gov (United States)

Mehta, Samata; Verstraelen, Hans; Peremans, Kathelijne; Villeirs, Geert; Vermeire, Simon; De Vos, Filip; Mehuys, Els; Remon, Jean Paul; Vervaet, Chris

2012-04-15

For any new vaginal dosage form, the distribution and retention in the vagina has to be assessed by in vivo evaluation. We evaluated the vaginal distribution and retention of starch-based pellets in sheep as live animal model by gamma scintigraphy (using Indium-111 DTPA as radiolabel) and in women via magnetic resonance imaging (MRI, using a gadolinium chelate as contrast agent). A conventional cream formulation was used as reference in both studies. Cream and pellets were administered to sheep (n=6) in a two period-two treatment study and to healthy female volunteers (n=6) via a randomized crossover trial. Pellets (filled into hard gelatin capsule) and cetomacrogol cream, both labeled with Indium-111 DTPA (for gamma scintigraphy) or with gadolinium chelate (for MRI) were evaluated for their intravaginal distribution and retention over a 24h period. Spreading in the vagina was assessed based on the part of the vagina covered with formulation (expressed in relation to the total vaginal length). Vaginal retention of the formulation was quantified based on the radioactivity remaining in the vaginal area (sheep study), or qualitatively evaluated (women study). Both trials indicated a rapid distribution of the cream within the vagina as complete coverage of the vaginal mucosa was seen 1h after dose administration. Clearance of the cream was rapid: about 10% activity remained in the vaginal area of the sheep 12h post-administration, while after 8h only a thin layer of cream was detected on the vaginal mucosa of women. After disintegration of the hard gelatin capsule, the pellet formulation gradually distributed over the entire vaginal mucosa. Residence time of the pellets in the vagina was longer compared to the semi-solid formulation: after 24h 23 ± 7% radioactivity was detected in the vaginal area of the sheep, while in women the pellet formulation was still detected throughout the vagina. A multi-particulate system containing starch-based pellets was identified as a

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

Science.gov (United States)

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

Directory of Open Access Journals (Sweden)

Neil O Carragher

2011-04-01

Full Text Available Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates.

Intelligent distributed medical image management

Science.gov (United States)

Garcia, Hong-Mei C.; Yun, David Y.

1995-05-01

The rapid advancements in high performance global communication have accelerated cooperative image-based medical services to a new frontier. Traditional image-based medical services such as radiology and diagnostic consultation can now fully utilize multimedia technologies in order to provide novel services, including remote cooperative medical triage, distributed virtual simulation of operations, as well as cross-country collaborative medical research and training. Fast (efficient) and easy (flexible) retrieval of relevant images remains a critical requirement for the provision of remote medical services. This paper describes the database system requirements, identifies technological building blocks for meeting the requirements, and presents a system architecture for our target image database system, MISSION-DBS, which has been designed to fulfill the goals of Project MISSION (medical imaging support via satellite integrated optical network) -- an experimental high performance gigabit satellite communication network with access to remote supercomputing power, medical image databases, and 3D visualization capabilities in addition to medical expertise anywhere and anytime around the country. The MISSION-DBS design employs a synergistic fusion of techniques in distributed databases (DDB) and artificial intelligence (AI) for storing, migrating, accessing, and exploring images. The efficient storage and retrieval of voluminous image information is achieved by integrating DDB modeling and AI techniques for image processing while the flexible retrieval mechanisms are accomplished by combining attribute- based and content-based retrievals.

An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles

Directory of Open Access Journals (Sweden)

Prakash Gangadaran

2018-02-01

Full Text Available Extracellular vesicles (EVs are currently being considered as promising drug delivery vehicles. EVs are naturally occurring vesicles that exhibit many characteristics favorable to serve as drug delivery vehicles. In addition, EVs have inherent properties for treatment of cancers and other diseases. For research and clinical translation of use of EVs as drug delivery vehicles, in vivo tracking of EVs is essential. The latest molecular imaging techniques enable the tracking of EVs in living animals. However, each molecular imaging technique has its certain advantages and limitations for the in vivo imaging of EVs; therefore, understanding the molecular imaging techniques is essential to select the most appropriate imaging technology to achieve the desired imaging goal. In this review, we summarize the characteristics of EVs as drug delivery vehicles and the molecular imaging techniques used in visualizing and monitoring EVs in in vivo environments. Furthermore, we provide a perceptual vision of EVs as drug delivery vehicles and in vivo monitoring of EVs using molecular imaging technologies.

Predictive typing of drug-induced neurological sufferings from studies of the distribution of labelled drugs

International Nuclear Information System (INIS)

Takasu, T.

1980-01-01

A drug given to an animal becomes widely distributed throughout the body, acting on the living mechanisms or structures, and is gradually excreted. Some drugs can remain in some parts of the body for a long period. For example, 14 C-chloramphenical was found to remain preferentially in the salivary gland, liver and bone marrow of mice 24 hours after its oral administration. If such a drug is given repeatedly, it could possibly accumulate gradually in these organs. Thus, when its accumulation in a particular part of the body exceeds a certain level, the living mechanism or structure may possibly be injured. The harmful effects of a drug in repeated administration are called its chronic toxicity. The author discusses whether it is possible to predict the toxicity of a drug by studying its distribution in relation to time, and, if possible, the points in time. This problem is studied especially in relation to the nervous system. (Auth.)

Direct visualization of in vitro drug mobilization from Lescol XL tablets using two-dimensional (19)F and (1)H magnetic resonance imaging.

Science.gov (United States)

Chen, Chen; Gladden, Lynn F; Mantle, Michael D

2014-02-03

This article reports the application of in vitro multinuclear ((19)F and (1)H) two-dimensional magnetic resonance imaging (MRI) to study both dissolution media ingress and drug egress from a commercial Lescol XL extended release tablet in a United States Pharmacopeia Type IV (USP-IV) dissolution cell under pharmacopoeial conditions. Noninvasive spatial maps of tablet swelling and dissolution, as well as the mobilization and distribution of the drug are quantified and visualized. Two-dimensional active pharmaceutical ingredient (API) mobilization and distribution maps were obtained via (19)F MRI. (19)F API maps were coregistered with (1)H T2-relaxation time maps enabling the simultaneous visualization of drug distribution and gel layer dynamics within the swollen tablet. The behavior of the MRI data is also discussed in terms of its relationship to the UV drug release behavior.

Development of Antibody–Drug Conjugates Using DDS and Molecular Imaging

Directory of Open Access Journals (Sweden)

Masahiro Yasunaga

2017-09-01

Full Text Available Antibody-drug conjugate (ADC, as a next generation of antibody therapeutics, is a combination of an antibody and a drug connected via a specialized linker. ADC has four action steps: systemic circulation, the enhanced permeability and retention (EPR effect, penetration within the tumor tissue, and action on cells, such as through drug delivery system (DDS drugs. An antibody with a size of about 10 nm has the same capacity for passive targeting as some DDS carriers, depending on the EPR effect. In addition, some antibodies are capable of active targeting. A linker is stable in the bloodstream but should release drugs efficiently in the tumor cells or their microenvironment. Thus, the linker technology is actually a typical controlled release technology in DDS. Here, we focused on molecular imaging. Fluorescent and positron emission tomography (PET imaging is useful for the visualization and evaluation of antibody delivery in terms of passive and active targeting in the systemic circulation and in tumors. To evaluate the controlled release of the ADC in the targeted area, a mass spectrometry imaging (MSI with a mass microscope, to visualize the drug released from ADC, was used. As a result, we succeeded in confirming the significant anti-tumor activity of anti-fibrin, or anti-tissue factor-ADC, in preclinical settings by using DDS and molecular imaging.

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

International Nuclear Information System (INIS)

Gulyas, Balazs; Halldin, Christer; Sandell, Johan; Farde, Lars; Sovago, Judit; Cselenyi, Zsolt; Vas, Adam; Kiss, Bela; Karpati, Egon

2002-01-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [ 11 C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [ 11 C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [ 11 C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

Science.gov (United States)

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

Science.gov (United States)

Rainsford, K D; Schweitzer, A; Brune, K

1981-04-01

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting. The object of this study was to establish if the distribution of these new NSAI drugs may contribute to changes in their side-, or therapeutic effects compared with the older drugs. All the NSAI drugs accumulated in those tissues wherein the principle therapeutic and side-effects are manifest. The accumulation in inflamed tissues occurs regardless of the structural type of NSAI drugs, i.e. with specific accumulation occurring in this tissue of the acidic drugs or their acidic metabolites. New aspects of the distribution of the acetyl moiety of aspirin are reported which may be significant in relation to the side-effects induced by this drug.

Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

Science.gov (United States)

Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

2016-02-01

Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

Directory of Open Access Journals (Sweden)

Papon Janine

2004-04-01

Full Text Available Abstract Background Analytical imaging by secondary ion mass spectrometry (SIMS provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing. Methods The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma. B16 melanoma cells were injected intravenously to C57BL6/J1/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis. Results Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc. while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue. Conclusion This study demonstrates the potential of SIMS microscopy, which allows the

The waiting time distribution as a graphical approach to epidemiologic measures of drug utilization

DEFF Research Database (Denmark)

Hallas, J; Gaist, D; Bjerrum, L

1997-01-01

that effectively conveys some essential utilization parameters for a drug. The waiting time distribution for a group of drug users is a charting of their first prescription presentations within a specified time window. For a drug used for chronic treatment, most current users will be captured at the beginning...... of the window. After a few months, the graph will be dominated by new, incident users. As examples, we present waiting time distributions for insulin, ulcer drugs, systemic corticosteroids, antidepressants, and disulfiram. Appropriately analyzed and interpreted, the waiting time distributions can provide...... information about the period prevalence, point prevalence, incidence, duration of use, seasonality, and rate of prescription renewal or relapse for specific drugs. Each of these parameters has a visual correlate. The waiting time distributions may be an informative supplement to conventional drug utilization...

The influence of drug distribution and drug-target binding on target occupancy : The rate-limiting step approximation

NARCIS (Netherlands)

Witte, de W.E.A.; Vauquelin, G.; Graaf, van der P.H.; Lange, de E.C.M.

2017-01-01

The influence of drug-target binding kinetics on target occupancy can be influenced by drug distribution and diffusion around the target, often referred to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased decline of the drug-target complex concentration as a result of a

Natural radioactivity distribution images and their educational uses

International Nuclear Information System (INIS)

Mori, Chizuo; Sumi, Tetsuo; Miyahara, Hiroshi; Uritani, Akira; Nishina, Kojiro

1999-01-01

Distribution images of natural radioactivities in vegetables, meat and porcelain works were obtained by use of Imaging Plate with very high sensitivity to radiations. A brochure titled 'Natural Radiations through Naked Eyes' was published in both Japanese and English which included the images mentioned above. In this paper, the method to obtain the distribution images of extremely low level natural radioactivity, the content of the brochure and the effect of it to the public are described. (author)

Natural radioactivity distribution images and their educational uses

Energy Technology Data Exchange (ETDEWEB)

Mori, Chizuo; Sumi, Tetsuo [Aichi Institute of Technology, Toyota, Aichi (Japan); Miyahara, Hiroshi; Uritani, Akira; Nishina, Kojiro

1999-09-01

Distribution images of natural radioactivities in vegetables, meat and porcelain works were obtained by use of Imaging Plate with very high sensitivity to radiations. A brochure titled 'Natural Radiations through Naked Eyes' was published in both Japanese and English which included the images mentioned above. In this paper, the method to obtain the distribution images of extremely low level natural radioactivity, the content of the brochure and the effect of it to the public are described. (author)

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

Energy Technology Data Exchange (ETDEWEB)

Gulyas, Balazs [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm (Sweden); Halldin, Christer; Sandell, Johan; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Sovago, Judit; Cselenyi, Zsolt [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Vas, Adam; Kiss, Bela; Karpati, Egon [Chemical Works of Gedeon Richter Ltd., Budapest (Hungary)

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [{sup 11}C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [{sup 11}C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [{sup 11}C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and

DNA nanomaterials for preclinical imaging and drug delivery.

Science.gov (United States)

Jiang, Dawei; England, Christopher G; Cai, Weibo

2016-10-10

Besides being the carrier of genetic information, DNA is also an excellent biological organizer to establish well-designed nanostructures in the fields of material engineering, nanotechnology, and biomedicine. DNA-based materials represent a diverse nanoscale system primarily due to their predictable base pairing and highly regulated conformations, which greatly facilitate the construction of DNA nanostructures with distinct shapes and sizes. Integrating the emerging advancements in bioconjugation techniques, DNA nanostructures can be readily functionalized with high precision for many purposes ranging from biosensors to imaging to drug delivery. Recent progress in the field of DNA nanotechnology has exhibited collective efforts to employ DNA nanostructures as smart imaging agents or delivery platforms within living organisms. Despite significant improvements in the development of DNA nanostructures, there is limited knowledge regarding the in vivo biological fate of these intriguing nanomaterials. In this review, we summarize the current strategies for designing and purifying highly-versatile DNA nanostructures for biological applications, including molecular imaging and drug delivery. Since DNA nanostructures may elicit an immune response in vivo, we also present a short discussion of their potential toxicities in biomedical applications. Lastly, we discuss future perspectives and potential challenges that may limit the effective preclinical and clinical employment of DNA nanostructures. Due to their unique properties, we predict that DNA nanomaterials will make excellent agents for effective diagnostic imaging and drug delivery, improving patient outcome in cancer and other related diseases in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

A Degree Distribution Optimization Algorithm for Image Transmission

Science.gov (United States)

Jiang, Wei; Yang, Junjie

2016-09-01

Luby Transform (LT) code is the first practical implementation of digital fountain code. The coding behavior of LT code is mainly decided by the degree distribution which determines the relationship between source data and codewords. Two degree distributions are suggested by Luby. They work well in typical situations but not optimally in case of finite encoding symbols. In this work, the degree distribution optimization algorithm is proposed to explore the potential of LT code. Firstly selection scheme of sparse degrees for LT codes is introduced. Then probability distribution is optimized according to the selected degrees. In image transmission, bit stream is sensitive to the channel noise and even a single bit error may cause the loss of synchronization between the encoder and the decoder. Therefore the proposed algorithm is designed for image transmission situation. Moreover, optimal class partition is studied for image transmission with unequal error protection. The experimental results are quite promising. Compared with LT code with robust soliton distribution, the proposed algorithm improves the final quality of recovered images obviously with the same overhead.

NQR: From imaging to explosives and drugs detection

International Nuclear Information System (INIS)

Osan, Tristan M.; Cerioni, Lucas M.C.; Forguez, Jose; Olle, Juan M.; Pusiol, Daniel J.

2007-01-01

The main aim of this work is to present an overview of the nuclear quadrupole resonance (NQR) spectroscopy capabilities for solid state imaging and detection of illegal substances, such as explosives and drugs. We briefly discuss the evolution of different NQR imaging techniques, in particular those involving spatial encoding which permit conservation of spectroscopic information. It has been shown that plastic explosives and other forbidden substances cannot be easily detected by means of conventional inspection techniques, such as those based on conventional X-ray technology. For this kind of applications, the experimental results show that the information inferred from NQR spectroscopy provides excellent means to perform volumetric and surface detection of dangerous explosive and drug compounds

[Frontiers in Live Bone Imaging Researches. Novel drug discovery by means of intravital bone imaging technology].

Science.gov (United States)

Ishii, Masaru

2015-06-01

Recent advances in intravital bone imaging technology has enabled us to grasp the real cellular behaviors and functions in vivo , revolutionizing the field of drug discovery for novel therapeutics against intractable bone diseases. In this chapter, I introduce various updated information on pharmacological actions of several antibone resorptive agents, which could only be derived from advanced imaging techniques, and also discuss the future perspectives of this new trend in drug discovery.

Software Image J to study soil pore distribution

Directory of Open Access Journals (Sweden)

Sabrina Passoni

2014-04-01

Full Text Available In the soil science, a direct method that allows the study of soil pore distribution is the bi-dimensional (2D digital image analysis. Such technique provides quantitative results of soil pore shape, number and size. The use of specific softwares for the treatment and processing of images allows a fast and efficient method to quantify the soil porous system. However, due to the high cost of commercial softwares, public ones can be an interesting alternative for soil structure analysis. The objective of this work was to evaluate the quality of data provided by the Image J software (public domain used to characterize the voids of two soils, characterized as Geric Ferralsol and Rhodic Ferralsol, from the southeast region of Brazil. The pore distribution analysis technique from impregnated soil blocks was utilized for this purpose. The 2D image acquisition was carried out by using a CCD camera coupled to a conventional optical microscope. After acquisition and treatment of images, they were processed and analyzed by the software Noesis Visilog 5.4® (chosen as the reference program and ImageJ. The parameters chosen to characterize the soil voids were: shape, number and pore size distribution. For both soils, the results obtained for the image total porosity (%, the total number of pores and the pore size distribution showed that the Image J is a suitable software to be applied in the characterization of the soil sample voids impregnated with resin.

Scanning ion images; analysis of pharmaceutical drugs at organelle levels

Science.gov (United States)

Larras-Regard, E.; Mony, M.-C.

1995-05-01

With the ion analyser IMS 4F used in microprobe mode, it is possible to obtain images of fields of 10 × 10 [mu]m2, corresponding to an effective magnification of 7000 with lateral resolution of 250 nm, technical characteristics that are appropriate for the size of cell organelles. It is possible to characterize organelles by their relative CN-, P- and S- intensities when the tissues are prepared by freeze fixation and freeze substitution. The recognition of organelles enables correlation of the tissue distribution of ebselen, a pharmaceutical drug containing selenium. The various metabolites characterized in plasma, bile and urine during biotransformation of ebselen all contain selenium, so the presence of the drug and its metabolites can be followed by images of Se. We were also able to detect the endogenous content of Se in tissue, due to the increased sensitivity of ion analysis in microprobe mode. Our results show a natural occurrence of Se in the border corresponding to the basal lamina of cells of proximal but not distal tubules of the kidney. After treatment of rats with ebselen, an additional site of Se is found in the lysosomes. We suggest that in addition to direct elimination of ebselen and its metabolites by glomerular filtration and urinary elimination, a second process of elimination may occur: Se compounds reaching the epithelial cells via the basal lamina accumulate in lysosomes prior to excretion into the tubular fluid. The technical developments of using the IMS 4F instrument in the microprobe mode and the improvement in preparation of samples by freeze fixation and substitution further extend the limit of ion analysis in biology. Direct imaging of trace elements and molecules marked with a tracer make it possible to determine their targets by comparison with images of subcellular structures. This is a promising advance in the study of pathways of compounds within tissues, cells and the whole organism.

PET IMAGING STUDIES IN DRUG ABUSE RESEARCH.

Energy Technology Data Exchange (ETDEWEB)

Fowler, J.S.; Volkow, N.D.; Ding, Y.S.; Logan, J.; Wang, G.J.

2001-01-29

There is overwhelming evidence that addiction is a disease of the brain (Leshner, 1997). Yet public perception that addiction is a reflection of moral weakness or a lack of willpower persists. The insidious consequence of this perception is that we lose sight of the fact that there are enormous medical consequences of addiction including the fact that a large fraction of the total deaths from cancer and heart disease are caused by smoking addiction. Ironically the medical school that educates physicians in addiction medicine and the cancer hospital that has a smoking cessation clinic are vanishingly rare and efforts at harm reduction are frequently met with a public indignation. Meanwhile the number of people addicted to substances is enormous and increasing particularly the addictions to cigarettes and alcohol. It is particularly tragic that addiction usually begins in adolescence and becomes a chronic relapsing problem and there are basically no completely effective treatments. Clearly we need to understand how drugs of abuse affect the brain and we need to be creative in using this information to develop effective treatments. Imaging technologies have played a major role in the conceptualization of addiction as a disease of the brain (Fowler et al., 1998a; Fowler et al., 1999a). New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology and medicine. This topic cuts across the medical specialties of neurology, psychiatry, cancer and heart disease because of the high medical, social and economic toll that drugs of abuse, including and especially the legal drugs, cigarettes and alcohol, take on society. In this chapter we will begin by highlighting the important role that chemistry has played in making it possible to quantitatively image the movement of drugs as well as their effects on the human brain

The use of web internet technologies to distribute medical images

International Nuclear Information System (INIS)

Deller, A.L.; Cheal, D.; Field, J.

1999-01-01

Full text: In the past, internet browsers were considered ineffective for image distribution. Today we have the technology to use internet standards for picture archive and communication systems (PACS) and teleradiology effectively. Advanced wavelet compression and state-of-the-art JAVA software allows us to distribute images on normal computer hardware. The use of vendor and database neutral software and industry-standard hardware has many advantages. This standards base approach avoids the costly rapid obsolescence of proprietary PACS and is cheaper to purchase and maintain. Images can be distributed around a hospital site, as well as outside the campus, quickly and inexpensively. It also allows integration between the Hospital Information System (HIS) and the Radiology Information System (RIS). Being able to utilize standard internet technologies and computer hardware for PACS is a cost-effective alternative. A system based on this technology can be used for image distribution, archiving, teleradiology and RIS integration. This can be done without expensive specialized imaging workstations and telecommunication systems. Web distribution of images allows you to send images to multiple places concurrently. A study can be within your Medical Imaging Department, as well as in the ward and on the desktop of referring clinicians - with a report. As long as there is a computer with an internet access account, high-quality images can be at your disposal 24 h a day. The importance of medical images for patient management makes them a valuable component of the patient's medical record. Therefore, an efficient system for displaying and distributing images can improve patient management and make your workplace more effective

Effects of image congruency on persuasiveness and recall in direct-to-consumer prescription drug advertising.

Science.gov (United States)

Kiernicki, Kristen; Helme, Donald W

2017-01-01

Although direct-to-consumer (DTC) prescription drug advertising is regulated by the U.S. Food and Drug Administration, content analyses suggest advertisers may not disclose drug risks in the same way they describe drug benefits. This study tests the relationship between image congruency in televised DTC advertisements, recall of risks/benefits, and perceived persuasiveness. Advertisements for Nasonex, Advair, and Lunesta were shown to college students in either their original (image incongruent) or modified (image neutral) form. Risks were easier to recall with image-neutral advertisements. Gender also had a significant interaction effect, suggesting that males and females process DTC advertisement differently.

Gender and images of heart disease in Scandinavian drug advertising.

Science.gov (United States)

Riska, Elianne; Heikell, Thomas

2007-01-01

This study examines the construction of the "heart disease candidate" in advertisements for cardiovascular drugs in Scandinavian medical journals. All advertisements for cardiovascular drugs (n = 603) in Scandinavian medical journals (Denmark, Finland, Norway, and Sweden) in 2005 were collected. Only advertisements that portray users (n = 289, 48% of the advertisements) were analyzed. The results show that coronary candidacy is constructed as a male condition in half of the advertisements for cardiovascular drugs. The advertisements suggest a gendering of heart disease: men are the major victims of heart failure and cardiac insufficiency, and women are in need of cholesterol-lowering drugs. The cardiovascular drug advertisements portray a restoration of men's hyperactive agency, valorized by means of sporty images, by drawing on masculinity as a fixed trait and behavior. Hypercholesterolemia as a woman's disease reproduces the tyranny of slimness for women: Only women's stoutness is medicalized, and there are no pictures of heavy men. The findings point to the public health implications of gendered images of coronary candidacy in medical advertising.

A study of the distribution of schistosomicidal drug H-3-7505 in mice

International Nuclear Information System (INIS)

Hao, T.

1985-01-01

The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of jaundice in the clinical practice. Moreover, the appearance of toxic reaction in nervous system may be related to the relatively high concentration of the drug distributed in the brain

Financial Effect of a Drug Distribution Model Change on a Health System.

Science.gov (United States)

Turingan, Erin M; Mekoba, Bijan C; Eberwein, Samuel M; Roberts, Patricia A; Pappas, Ashley L; Cruz, Jennifer L; Amerine, Lindsey B

2017-06-01

Background: Drug manufacturers change distribution models based on patient safety and product integrity needs. These model changes can limit health-system access to medications, and the financial impact on health systems can be significant. Objective: The primary aim of this study was to determine the health-system financial impact of a manufacturer's change from open to limited distribution for bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). The secondary aim was to identify opportunities to shift administration to outpatient settings to support formulary change. Methods: To assess the financial impact on the health system, the cost minus discount was applied to total drug expenditure during a 1-year period after the distribution model change. The opportunity analysis was conducted for three institutions within the health system through chart review of each inpatient administration. Opportunity cost was the sum of the inpatient administration cost and outpatient administration margin. Results: The total drug expenditure for the study period was $26 427 263. By applying the cost minus discount, the financial effect of the distribution model change was $1 393 606. A total of 387 administrations were determined to be opportunities to be shifted to the outpatient setting. During the study period, the total opportunity cost was $1 766 049. Conclusion: Drug expenditure increased for the health system due to the drug distribution model change and loss of cost minus discount. The opportunity cost of shifting inpatient administrations could offset the increase in expenditure. It is recommended to restrict bevacizumab, rituximab, and trastuzumab through Pharmacy & Therapeutics Committees to outpatient use where clinically appropriate.

Fluorescence optical imaging in anticancer drug delivery

Czech Academy of Sciences Publication Activity Database

Etrych, Tomáš; Lucas, H.; Janoušková, Olga; Chytil, Petr; Mueller, T.; Mäder, K.

2016-01-01

Roč. 226, 28 March (2016), s. 168-181 ISSN 0168-3659 R&D Projects: GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : fluorescence imaging * drug delivery * theranostics Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.786, year: 2016

PBCA-based polymeric microbubbles for molecular imaging and drug delivery

NARCIS (Netherlands)

Koczera, Patrick; Appold, Lia; Shi, Yang; Liu, Mengjiao; Dasgupta, Anshuman; Pathak, Vertika; Ojha, Tarun; Fokong, Stanley; Wu, Zhuojun; Van Zandvoort, Marc; Iranzo, Olga; Kuehne, Alexander J C; Pich, Andrij; Kiessling, Fabian; Lammers, Twan

2017-01-01

Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A magnetic nanoparticle stabilized gas containing emulsion for multimodal imaging and triggered drug release.

Science.gov (United States)

Guo, Wei; Li, Diancheng; Zhu, Jia-an; Wei, Xiaohui; Men, Weiwei; Yin, Dazhi; Fan, Mingxia; Xu, Yuhong

2014-06-01

To develop a multimodal imaging guided and triggered drug delivery system based on a novel emulsion formulation composed of iron oxide nanoparticles, nanoscopic bubbles, and oil containing drugs. Iron oxide paramagnetic nanoparticles were synthesized and modified with surface conjugation of polyethylenimide (PEI) or Bovine Serum Albumin (BSA). Both particles were used to disperse and stabilize oil in water emulsions containing coumarin-6 as the model drug. Sulfur hexafluoride was introduced into the oil phase to form nanoscopic bubbles inside the emulsions. The resulted gas containing emulsions were evaluated for their magnetic resonance (MR) and ultrasound (US) imaging properties. The drug release profile triggered by ultrasound was also examined. We have successfully prepared the highly integrated multi-component emulsion system using the surface modified iron oxide nanoparticles to stabilize the interfaces. The resulted structure had distinctive MR and US imaging properties. Upon application of ultrasound waves, the gas containing emulsion would burst and encapsulated drug could be released. The integrated emulsion formulation was multifunctional with paramagnetic, sono-responsive and drug-carrying characteristics, which may have potential applications for disease diagnosis and imaging guided drug release.

Mass Spectrometry Imaging of Drugs of Abuse in Hair.

Science.gov (United States)

Flinders, Bryn; Cuypers, Eva; Porta, Tiffany; Varesio, Emmanuel; Hopfgartner, Gérard; Heeren, Ron M A

2017-01-01

Hair testing is a powerful tool routinely used for the detection of drugs of abuse. The analysis of hair is highly advantageous as it can provide prolonged drug detectability versus that in biological fluids and chronological information about drug intake based on the average growth of hair. However, current methodology requires large amounts of hair samples and involves complex time-consuming sample preparation followed by gas or liquid chromatography coupled with mass spectrometry. Mass spectrometry imaging is increasingly being used for the analysis of single hair samples, as it provides more accurate and visual chronological information in single hair samples.Here, two methods for the preparation of single hair samples for mass spectrometry imaging are presented.The first uses an in-house built cutting apparatus to prepare longitudinal sections, the second is a method for embedding and cryo-sectioning hair samples in order to prepare cross-sections all along the hair sample.

[Drug users' quality of life, self-esteem and self-image].

Science.gov (United States)

Silveira, Camila da; Meyer, Carolina; Souza, Gabriel Renaldo de; Ramos, Manoella de Oliveira; Souza, Melissa de Carvalho; Monte, Fernanda Guidarini; Guimarães, Adriana Coutinho de Azevedo; Parcias, Sílvia Rosane

2013-07-01

This cross-sectional study aimed to investigate the quality of life, self-esteem and self-image among drug users of São José Institute in São José in the State of Santa Catarina. The accessibility sample was comprised of 100 male patients with a mean age of 43.0 ± 10.7, who had studied for a mean period of 8.4 ± 3.7 years. 48% of them were married and had been hospitalized or treated for a minimum period of seven days. When the participants were not hospitalized they lived with wives and children (23%), were married (48%), employed (72%), were part of income level B (58%), had done something they regret in their lives (57%) and perceived their health as good (57%). Regarding quality of life, the highest scores were found in the environmental domain (65%) and the lowest scores were in the psychological domain (58%). All patients were taking medication and had low self-esteem and self-image (77% and 96% respectively). The absence of interference of the quality of life on self-esteem and self-image of the drug users was observed by means of logistic regression. Positive quality of life did not interfere in changes in low self-esteem and self-image of drug users.

Microencapsulation of indocyanine green for potential applications in image-guided drug delivery.

Science.gov (United States)

Zhu, Zhiqiang; Si, Ting; Xu, Ronald X

2015-02-07

We present a novel process to encapsulate indocyanine green (ICG) in liposomal droplets at high concentration for potential applications in image-guided drug delivery. The microencapsulation process follows two consecutive steps of droplet formation by liquid-driven coaxial flow focusing (LDCFF) and solvent removal by oil phase dewetting. These biocompatible lipid vesicles may have important applications in drug delivery and fluorescence imaging.

Role of imaging techniques in the evaluation of cardiovascular drugs

International Nuclear Information System (INIS)

Sugishita, Yasuro; Matsuda, Mitsuo; Ajisaka, Ryuichi

1985-01-01

In order to investigate the role of imaging in the evaluation of medical treatment in heart diseases, radionuclide angiocardiography, echocardiography and Doppler echocardiography were applied in the cases of various kinds of heart diseases. Acute and chronic effects of antianginal drugs (nitrates, calcium antagonists and beta-blockers) could be evaluated by exercise radionuclide angiocardiography or exercise echocardiography in the cases of effort angina. The effects of the drugs changing myocardial contractility, preload or afterload could be evaluated by echocardiography in various kinds of heart diseases, including valvular heart biseases. The effect of calcium antagonists in improving diastolic function in hypertrophic cardiomyopathy could be evaluated by echocardiography or Doppler echocardiography. In conclusion, imaging techniqus are valuable and useful methods to evaluate the effects of cardiovascular drugs, by offering various informations. (author)

Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions in Spiked Skim Milk and Whey.

Science.gov (United States)

Shappell, Nancy W; Shelver, Weilin L; Lupton, Sara J; Fanaselle, Wendy; Van Doren, Jane M; Hakk, Heldur

2017-02-01

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labeled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R 2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R 2 = 0.95). Distribution of drugs was concentration independent over the range tested (20-2000 nM). With the exception of thiabendazole and ivermectin, more drug was associated with whey protein than casein on a nmol/g protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.

Imaging biomarkers as surrogate endpoints for drug development

International Nuclear Information System (INIS)

Richter, Wolf S.

2006-01-01

The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

Verification of IMRT dose distributions using a water beam imaging system

International Nuclear Information System (INIS)

Li, J.S.; Boyer, Arthur L.; Ma, C.-M.

2001-01-01

A water beam imaging system (WBIS) has been developed and used to verify dose distributions for intensity modulated radiotherapy using dynamic multileaf collimator. This system consisted of a water container, a scintillator screen, a charge-coupled device camera, and a portable personal computer. The scintillation image was captured by the camera. The pixel value in this image indicated the dose value in the scintillation screen. Images of radiation fields of known spatial distributions were used to calibrate the device. The verification was performed by comparing the image acquired from the measurement with a dose distribution from the IMRT plan. Because of light scattering in the scintillator screen, the image was blurred. A correction for this was developed by recognizing that the blur function could be fitted to a multiple Gaussian. The blur function was computed using the measured image of a 10 cmx10 cm x-ray beam and the result of the dose distribution calculated using the Monte Carlo method. Based on the blur function derived using this method, an iterative reconstruction algorithm was applied to recover the dose distribution for an IMRT plan from the measured WBIS image. The reconstructed dose distribution was compared with Monte Carlo simulation result. Reasonable agreement was obtained from the comparison. The proposed approach makes it possible to carry out a real-time comparison of the dose distribution in a transverse plane between the measurement and the reference when we do an IMRT dose verification

Interference Imaging of Refractive Index Distribution in Thin Samples

Directory of Open Access Journals (Sweden)

Ivan Turek

2004-01-01

Full Text Available There are three versions of interference imaging of refractive index distribution in thin samples suggested in this contribution. These are based on imaging of interference field created by waves reflected from the front and the back sample surface or imaging of interference field of Michelson or Mach-Zehnder interferometer with the sample put in one of the interferometers arm. The work discusses the advantages and disadvantages of these techniques and presents the results of imaging of refrective index distribution in photorefractive record of a quasi-harmonic optical field in thin LiNbO3 crystal sample.

Visualization of metallodrugs in single cells by secondary ion mass spectrometry imaging.

Science.gov (United States)

Wu, Kui; Jia, Feifei; Zheng, Wei; Luo, Qun; Zhao, Yao; Wang, Fuyi

2017-07-01

Secondary ion mass spectrometry, including nanoscale secondary ion mass spectrometry (NanoSIMS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), has emerged as a powerful tool for biological imaging, especially for single cell imaging. SIMS imaging can provide information on subcellular distribution of endogenous and exogenous chemicals, including metallodrugs, from membrane through to cytoplasm and nucleus without labeling, and with high spatial resolution and chemical specificity. In this mini-review, we summarize recent progress in the field of SIMS imaging, particularly in the characterization of the subcellular distribution of metallodrugs. We anticipate that the SIMS imaging method will be widely applied to visualize subcellular distributions of drugs and drug candidates in single cells, exerting significant influence on early drug evaluation and metabolism in medicinal and pharmaceutical chemistry. Recent progress of SIMS applications in characterizing the subcellular distributions of metallodrugs was summarized.

Integration of distributed computing into the drug discovery process.

Science.gov (United States)

von Korff, Modest; Rufener, Christian; Stritt, Manuel; Freyss, Joel; Bär, Roman; Sander, Thomas

2011-02-01

Grid computing offers an opportunity to gain massive computing power at low costs. We give a short introduction into the drug discovery process and exemplify the use of grid computing for image processing, docking and 3D pharmacophore descriptor calculations. The principle of a grid and its architecture are briefly explained. More emphasis is laid on the issues related to a company-wide grid installation and embedding the grid into the research process. The future of grid computing in drug discovery is discussed in the expert opinion section. Most needed, besides reliable algorithms to predict compound properties, is embedding the grid seamlessly into the discovery process. User friendly access to powerful algorithms without any restrictions, that is, by a limited number of licenses, has to be the goal of grid computing in drug discovery.

Optimization of Sample Preparation and Instrumental Parameters for the Rapid Analysis of Drugs of Abuse in Hair samples by MALDI-MS/MS Imaging

Science.gov (United States)

Flinders, Bryn; Beasley, Emma; Verlaan, Ricky M.; Cuypers, Eva; Francese, Simona; Bassindale, Tom; Clench, Malcolm R.; Heeren, Ron M. A.

2017-08-01

Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) has been employed to rapidly screen longitudinally sectioned drug user hair samples for cocaine and its metabolites using continuous raster imaging. Optimization of the spatial resolution and raster speed were performed on intact cocaine contaminated hair samples. The optimized settings (100 × 150 μm at 0.24 mm/s) were subsequently used to examine longitudinally sectioned drug user hair samples. The MALDI-MS/MS images showed the distribution of the most abundant cocaine product ion at m/z 182. Using the optimized settings, multiple hair samples obtained from two users were analyzed in approximately 3 h: six times faster than the standard spot-to-spot acquisition method. Quantitation was achieved using longitudinally sectioned control hair samples sprayed with a cocaine dilution series. A multiple reaction monitoring (MRM) experiment was also performed using the `dynamic pixel' imaging method to screen for cocaine and a range of its metabolites, in order to differentiate between contaminated hairs and drug users. Cocaine, benzoylecgonine, and cocaethylene were detectable, in agreement with analyses carried out using the standard LC-MS/MS method. [Figure not available: see fulltext.

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What actions must I take to control the... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Distribution § 212.90 What actions must I take to control the distribution of PET drug products? (a) Written distribution procedures. You must establish...

Spatiotemporal Quantification of Local Drug Delivery Using MRI

Directory of Open Access Journals (Sweden)

Morgan B. Giers

2013-01-01

Full Text Available Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI of local drug delivery was performed to visualize and quantify the time resolved distribution of MRI contrast agents. Three-dimensional maps (generated from -weighted images with varied were processed using noise-reducing filtering. A segmented region of contrast, from a thresholded image, was converted to concentration maps using the equation , where and are the precontrast and postcontrast map values, respectively. In this technique, a uniform estimated value for was used. Error estimations were performed for each step. The practical usefulness of this method was assessed using comparisons between devices located in different locations both with and without contrast. The method using a uniform , requiring no registration of pre- and postcontrast image volumes, was compared to a method using either affine or deformation registrations.

Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery.

Science.gov (United States)

Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; Ur Rehman, Asim; Ud Din, Fakhar

2017-08-17

Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery

Science.gov (United States)

Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; ur Rehman, Asim; ud Din, Fakhar

2017-08-01

Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

Science.gov (United States)

Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

2016-06-14

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

International Nuclear Information System (INIS)

Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

2010-01-01

Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

Study of component distribution in pharmaceutical binary powder mixtures by near infrared chemical imaging

Directory of Open Access Journals (Sweden)

Manel Bautista

2012-12-01

Full Text Available Near infrared chemical imaging (NIR-CI has recently emerged as an effective technique for extracting spatial information from pharmaceutical products in an expeditious, non-destructive and non-invasive manner. These features have turned it into a useful tool for controlling various steps in drug production processes. Imaging techniques provide a vast amount of both spatial and spectral information that can be acquired in a very short time. Such a huge amount of data requires the use of efficient and fast methods to extract the relevant information. Chemometric methods have proved especially useful for this purpose. In this study, we assessed the usefulness of the correlation coefficient (CC between the spectra of samples, the pure spectra of the active pharmaceutical ingredient (API and we assessed the excipients to check for correct ingredient distribution in pharmaceutical binary preparations blended in the laboratory. Visual information about pharmaceutical component distribution can be obtained by using the CC. The performance of this model construction methodology for binary samples was compared with other various common multivariate methods including partial least squares, multivariate curve resolution and classical least squares. Based on the results, correlation coefficients are a powerful tool for the rapid assessment of correct component distribution and for quantitative analysis of pharmaceutical binary formulations. For samples of three or more components it has been shown that if the objective is only to determine uniformity of blending, then the CC image map is very good for this, and easy and fast to compute.

Ionic Copolymer-Magnetite Complexes for Magnetic Resonance Imaging and Drug Delivery

OpenAIRE

Zhang, Rui

2015-01-01

This thesis is focused on the design, synthesis and characterization of magnetite-ionic copolymer complexes as nanocarriers for drug delivery and magnetic resonance imaging. The polymers included phosphonate and carboxylate-containing graft and block copolymers. Oleic-acid coated magnetite nanoparticles (8-nm and 16-nm diameters) were investigated. Cisplatin and carboplatin were used as sample drugs. The potentials of the magnetite-ionomer complexes as dual drug delivery carriers and magneti...

Experimental design and instability analysis of coaxial electrospray process for microencapsulation of drugs and imaging agents.

Science.gov (United States)

Si, Ting; Zhang, Leilei; Li, Guangbin; Roberts, Cynthia J; Yin, Xiezhen; Xu, Ronald

2013-07-01

Recent developments in multimodal imaging and image-guided therapy requires multilayered microparticles that encapsulate several imaging and therapeutic agents in the same carrier. However, commonly used microencapsulation processes have multiple limitations such as low encapsulation efficiency and loss of bioactivity for the encapsulated biological cargos. To overcome these limitations, we have carried out both experimental and theoretical studies on coaxial electrospray of multilayered microparticles. On the experimental side, an improved coaxial electrospray setup has been developed. A customized coaxial needle assembly combined with two ring electrodes has been used to enhance the stability of the cone and widen the process parameter range of the stable cone-jet mode. With this assembly, we have obtained poly(lactide-co-glycolide) microparticles with fine morphology and uniform size distribution. On the theoretical side, an instability analysis of the coaxial electrified jet has been performed based on the experimental parameters. The effects of process parameters on the formation of different unstable modes have been studied. The reported experimental and theoretical research represents a significant step toward quantitative control and optimization of the coaxial electrospray process for microencapsulation of multiple drugs and imaging agents in multimodal imaging and image-guided therapy.

Radioiodination and Biological Evaluation of some Drugs for Inflammatory Foci Imaging

International Nuclear Information System (INIS)

El Refaie, M.S.A.

2011-01-01

A radiopharmaceutical is defined as a chemical or pharmaceutical preparation labeled with a radionuclide in tracer or therapeutic concentration, used as a diagnostic or therapeutic agent. A radiopharmaceutical agent is usually administrated into a vein. Depending on which type of scan is being performed, the imaging will be done either immediately, a few hours later, or even several days after the injection. Imaging time varies, generally ranging from 20 to 45 minutes.In this thesis, we are more interested in the drugs that can be used for the treatment of all kinds of inflammation whether septic or aseptic. The inflammation by itself can be a controllable disease, but as the inflammation, specially the chronic type, can be the reason and the beginning of many more serious diseases as autoimmune disease, pulmonary disease, cardiovascular disease, neurological disease and cancer, the study and the early diagnosis of the inflammation can prevent many future problems for the patient. The study of the inflammation has been discussed before by labeling drugs with Iodine-125 for the imaging of inflammatory foci like etodolac, meloxicam, piroxicam and other drugs.

Precision Statistical Analysis of Images Based on Brightness Distribution

Directory of Open Access Journals (Sweden)

Muzhir Shaban Al-Ani

2017-07-01

Full Text Available Study the content of images is considered an important topic in which reasonable and accurate analysis of images are generated. Recently image analysis becomes a vital field because of huge number of images transferred via transmission media in our daily life. These crowded media with images lead to highlight in research area of image analysis. In this paper, the implemented system is passed into many steps to perform the statistical measures of standard deviation and mean values of both color and grey images. Whereas the last step of the proposed method concerns to compare the obtained results in different cases of the test phase. In this paper, the statistical parameters are implemented to characterize the content of an image and its texture. Standard deviation, mean and correlation values are used to study the intensity distribution of the tested images. Reasonable results are obtained for both standard deviation and mean value via the implementation of the system. The major issue addressed in the work is concentrated on brightness distribution via statistical measures applying different types of lighting.

Label-free detection of cellular drug responses by high-throughput bright-field imaging and machine learning.

Science.gov (United States)

Kobayashi, Hirofumi; Lei, Cheng; Wu, Yi; Mao, Ailin; Jiang, Yiyue; Guo, Baoshan; Ozeki, Yasuyuki; Goda, Keisuke

2017-09-29

In the last decade, high-content screening based on multivariate single-cell imaging has been proven effective in drug discovery to evaluate drug-induced phenotypic variations. Unfortunately, this method inherently requires fluorescent labeling which has several drawbacks. Here we present a label-free method for evaluating cellular drug responses only by high-throughput bright-field imaging with the aid of machine learning algorithms. Specifically, we performed high-throughput bright-field imaging of numerous drug-treated and -untreated cells (N = ~240,000) by optofluidic time-stretch microscopy with high throughput up to 10,000 cells/s and applied machine learning to the cell images to identify their morphological variations which are too subtle for human eyes to detect. Consequently, we achieved a high accuracy of 92% in distinguishing drug-treated and -untreated cells without the need for labeling. Furthermore, we also demonstrated that dose-dependent, drug-induced morphological change from different experiments can be inferred from the classification accuracy of a single classification model. Our work lays the groundwork for label-free drug screening in pharmaceutical science and industry.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

Science.gov (United States)

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Web Based Distributed Coastal Image Analysis System, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — This project develops Web based distributed image analysis system processing the Moderate Resolution Imaging Spectroradiometer (MODIS) data to provide decision...

Imaging neurotransmitter release by drugs of abuse.

Science.gov (United States)

Martinez, Diana; Narendran, Rajesh

2010-01-01

Previous studies have shown that imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers that are specific for brain dopamine receptors can be used to indirectly image the change in the levels of neurotransmitters within the brain. Most of the studies in addiction have focused on dopamine, since the dopamine neurons that project to the striatum have been shown to play a critical role in mediating addictive behavior. These imaging studies have shown that increased extracellular dopamine produced by psychostimulants can be measured with PET and SPECT. However, there are some technical issues associated with imaging changes in dopamine, and these are reviewed in this chapter. Among these are the loss of sensitivity, the time course of dopamine pulse relative to PET and SPECT imaging, and the question of affinity state of the receptor. In addition, animal studies have shown that most drugs of abuse increase extracellular dopamine in the striatum, yet not all produce a change in neurotransmitter that can be measured. As a result, imaging with a psychostimulant has become the preferred method for imaging presynaptic dopamine transmission, and this method has been used in studies of addiction. The results of these studies suggest that cocaine and alcohol addiction are associated with a loss of dopamine transmission, and a number of studies show that this loss correlates with severity of disease.

High resolution Cerenkov light imaging of induced positron distribution in proton therapy

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Seiichi, E-mail: s-yama@met.nagoya-u.ac.jp; Fujii, Kento; Morishita, Yuki; Okumura, Satoshi; Komori, Masataka [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Aichi 461-8673 (Japan); Toshito, Toshiyuki [Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Aichi 462-8508 (Japan)

2014-11-01

Purpose: In proton therapy, imaging of the positron distribution produced by fragmentation during or soon after proton irradiation is a useful method to monitor the proton range. Although positron emission tomography (PET) is typically used for this imaging, its spatial resolution is limited. Cerenkov light imaging is a new molecular imaging technology that detects the visible photons that are produced from high-speed electrons using a high sensitivity optical camera. Because its inherent spatial resolution is much higher than PET, the authors can measure more precise information of the proton-induced positron distribution with Cerenkov light imaging technology. For this purpose, they conducted Cerenkov light imaging of induced positron distribution in proton therapy. Methods: First, the authors evaluated the spatial resolution of our Cerenkov light imaging system with a {sup 22}Na point source for the actual imaging setup. Then the transparent acrylic phantoms (100 × 100 × 100 mm{sup 3}) were irradiated with two different proton energies using a spot scanning proton therapy system. Cerenkov light imaging of each phantom was conducted using a high sensitivity electron multiplied charge coupled device (EM-CCD) camera. Results: The Cerenkov light’s spatial resolution for the setup was 0.76 ± 0.6 mm FWHM. They obtained high resolution Cerenkov light images of the positron distributions in the phantoms for two different proton energies and made fused images of the reference images and the Cerenkov light images. The depths of the positron distribution in the phantoms from the Cerenkov light images were almost identical to the simulation results. The decay curves derived from the region-of-interests (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can be used for estimating the half-life of the radionuclide components of positrons. Conclusions: High resolution Cerenkov light imaging of proton-induced positron distribution was possible. The

High resolution Cerenkov light imaging of induced positron distribution in proton therapy

International Nuclear Information System (INIS)

Yamamoto, Seiichi; Fujii, Kento; Morishita, Yuki; Okumura, Satoshi; Komori, Masataka; Toshito, Toshiyuki

2014-01-01

Purpose: In proton therapy, imaging of the positron distribution produced by fragmentation during or soon after proton irradiation is a useful method to monitor the proton range. Although positron emission tomography (PET) is typically used for this imaging, its spatial resolution is limited. Cerenkov light imaging is a new molecular imaging technology that detects the visible photons that are produced from high-speed electrons using a high sensitivity optical camera. Because its inherent spatial resolution is much higher than PET, the authors can measure more precise information of the proton-induced positron distribution with Cerenkov light imaging technology. For this purpose, they conducted Cerenkov light imaging of induced positron distribution in proton therapy. Methods: First, the authors evaluated the spatial resolution of our Cerenkov light imaging system with a 22 Na point source for the actual imaging setup. Then the transparent acrylic phantoms (100 × 100 × 100 mm 3 ) were irradiated with two different proton energies using a spot scanning proton therapy system. Cerenkov light imaging of each phantom was conducted using a high sensitivity electron multiplied charge coupled device (EM-CCD) camera. Results: The Cerenkov light’s spatial resolution for the setup was 0.76 ± 0.6 mm FWHM. They obtained high resolution Cerenkov light images of the positron distributions in the phantoms for two different proton energies and made fused images of the reference images and the Cerenkov light images. The depths of the positron distribution in the phantoms from the Cerenkov light images were almost identical to the simulation results. The decay curves derived from the region-of-interests (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can be used for estimating the half-life of the radionuclide components of positrons. Conclusions: High resolution Cerenkov light imaging of proton-induced positron distribution was possible. The authors

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

Science.gov (United States)

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

77 FR 59156 - Antimicrobial Animal Drug Sales and Distribution Reporting; Extension of Comment Period

Science.gov (United States)

2012-09-26

.... FDA-2012-N-0447] Antimicrobial Animal Drug Sales and Distribution Reporting; Extension of Comment... its regulations relating to records and reports for approved antimicrobial new animal drugs. The... obtaining additional data and information about the extent of antimicrobial drug use in food-producing...

Real-time UV imaging of piroxicam diffusion and distribution from oil solutions into gels mimicking the subcutaneous matrix.

Science.gov (United States)

Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan; Jensen, Henrik; Larsen, Claus; Østergaard, Jesper

2012-05-12

A novel real-time UV imaging approach for non-intrusive investigation of the diffusion and partitioning phenomena occurring during piroxicam release from medium chain triglyceride (MCT) solution into two hydrogel matrices is described. Two binary polymer/buffer gel matrices, 0.5% (w/v) agarose and 25% (w/v) Pluronic F127, were applied as simple models mimicking the subcutaneous tissue. The evolution of the absorbance maps as a function of time provided detailed information on the piroxicam release processes upon the exposure of the gel matrices to MCT. Using calibration curves, the concentration maps of piroxicam in the UV imaging area were determined. Regression of the longitudinal concentration-distance profiles, which were obtained using expressions derived from Fick's second law, provided the diffusivity and the distribution coefficients of piroxicam penetrated into the gels. The obtained MCT-agarose (pH 7.4) distribution coefficient of 1.4 was identical to the MCT-aqueous (pH 7.4) distribution coefficient determined by the shake-flask method whereas that of the MCT-Pluronic F127 system was four times less. The experimental data show that UV imaging may have considerable potential for investigating the transport properties of drug formulations intended for the subcutaneous administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Experimental protocols for behavioral imaging: seeing animal models of drug abuse in a new light.

Science.gov (United States)

Aarons, Alexandra R; Talan, Amanda; Schiffer, Wynne K

2012-01-01

Behavioral neuroimaging is a rapidly evolving discipline that represents a marriage between the fields of behavioral neuroscience and preclinical molecular imaging. This union highlights the changing role of imaging in translational research. Techniques developed for humans are now widely applied in the study of animal models of brain disorders such as drug addiction. Small animal or preclinical imaging allows us to interrogate core features of addiction from both behavioral and biological endpoints. Snapshots of brain activity allow us to better understand changes in brain function and behavior associated with initial drug exposure, the emergence of drug escalation, and repeated bouts of drug withdrawal and relapse. Here we review the development and validation of new behavioral imaging paradigms and several clinically relevant radiotracers used to capture dynamic molecular events in behaving animals. We will discuss ways in which behavioral imaging protocols can be optimized to increase throughput and quantitative methods. Finally, we discuss our experience with the practical aspects of behavioral neuroimaging, so investigators can utilize effective animal models to better understand the addicted brain and behavior.

Drug quality in South Africa: perceptions of key players involved in medicines distribution.

Science.gov (United States)

Patel, Aarti; Norris, Pauline; Gauld, Robin; Rades, Thomas

2009-01-01

Substandard medicines contribute to poor public health and affect development, especially in the developing world. However knowledge of how manufacturers, distributors and providers understand the concept of drug quality and what strategies they adopt to ensure drug quality is limited, particularly in the developing world. The purpose of this paper is to explore pharmaceutical manufacturers', distributors' and providers' perceptions of drug quality in South Africa and how they ensure the quality of drugs during the distribution process. The approach taken was qualitative data collection through key informant interviews using a semi-structured interview guide. Transcripts were analysed thematically in Johannesburg, Pretoria and Durban, South Africa. Participants were recruited purposefully from a South African pharmaceutical manufacturer, SA subsidiaries of international manufacturers, national distribution companies, national wholesaler, public and private sector pharmacists, and a dispensing doctor. In total, ten interviews were conducted. Participants described drug quality in terms of the product and the processes involved in manufacturing and handling the product. Participants identified purchasing registered medicines from licensed suppliers, use of standard operating procedures, and audits between manufacturer and distributor and/or provider as key strategies employed to protect medicine quality. Effective communication amongst all stakeholders, especially in terms of providing feedback regarding complaints about medicine quality, appears as a potential area of concern, which would benefit from further research. The paper hightlights that ensuring medicine quality should be a shared responsibility amongst all involved in the distribution process to prevent medicines moving from one distribution system (public) into another (private).

Cardiac drugs used in cross-sectional cardiac imaging: what the radiologist needs to know

International Nuclear Information System (INIS)

McParland, P.; Nicol, E.D.; Harden, S.P.

2010-01-01

The demand for cross-sectional imaging of the heart is increasing dramatically and in many centres these imaging techniques are being performed by radiologists. Although radiologists are familiar with the computed tomography (CT) and magnetic resonance imaging (MRI) techniques to generate high-quality images and with using contrast agents, many are less familiar with administering the drugs necessary to perform CT coronary angiography and cardiac MR reliably. The aim of this article is to give an overview of the indications for and the contraindications to administering cardiac drugs in cross-sectional imaging departments. We also outline the complications that may be encountered and provide advice on how to treat these complications when they occur.

A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human

International Nuclear Information System (INIS)

Poulin, Patrick; Ekins, Sean; Theil, Frank-Peter

2011-01-01

A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V ss ) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V ss for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V ss of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models.

[Methodology for Identification of Inverse Drug Distribution, Spain].

Science.gov (United States)

López Pérez, M Arantzazu; Muñoz Arias, Mariano; Vázquez Mourelle, Raquel

2016-04-04

The phenomenon of reverse drug trafficking in the legal supply chain is an unlawful practice to serious risks to public health. The aims was to identify proactively pharmacies that carry out these illegal activities. An analysis was performed through the crossing billing data to SAS of 52 million packs of medicines for the 496 pharmacies in the province over a period of 29 months with the drug packaging data supplied by the distribution entities of the province with the implementation of specific indicator defined called 'percentage overbought' allows us to detect those pharmacies at high risk of being involved in this illicit trade. It was tested in two pharmacies one rural and other urban a detour of 5.130 medicine containers and an illicit profit obtained from € 9,591.78 for the first and 9.982 packaging and € 26,885.11 for the second; they had gone unnoticed in previous inspections. The methodology implemented to define a profile of infringing pharmacies high risk in these illicit practices, identify new ones that had not been sanctioned, weigh the drugs for illegal trade and to identify new drugs subject to diversion; also added as a challenge, it helps to adjust accurately and effectively calculate the illicit profit obtained.

Imaging of current distributions in superconducting thin film structures

International Nuclear Information System (INIS)

Doenitz, D.

2006-01-01

Local analysis plays an important role in many fields of scientific research. However, imaging methods are not very common in the investigation of superconductors. For more than 20 years, Low Temperature Scanning Electron Microscopy (LTSEM) has been successfully used at the University of Tuebingen for studying of condensed matter phenomena, especially of superconductivity. In this thesis LTSEM was used for imaging current distributions in different superconducting thin film structures: - Imaging of current distributions in Josephson junctions with ferromagnetic interlayer, also known as SIFS junctions, showed inhomogeneous current transport over the junctions which directly led to an improvement in the fabrication process. An investigation of improved samples showed a very homogeneous current distribution without any trace of magnetic domains. Either such domains were not present or too small for imaging with the LTSEM. - An investigation of Nb/YBCO zigzag Josephson junctions yielded important information on signal formation in the LTSEM both for Josephson junctions in the short and in the long limit. Using a reference junction our signal formation model could be verified, thus confirming earlier results on short zigzag junctions. These results, which could be reproduced in this work, support the theory of d-wave symmetry in the superconducting order parameter of YBCO. Furthermore, investigations of the quasiparticle tunneling in the zigzag junctions showed the existence of Andreev bound states, which is another indication of the d-wave symmetry in YBCO. - The LTSEM study of Hot Electron Bolometers (HEB) allowed the first successful imaging of a stable 'Hot Spot', a self-heating region in HEB structures. Moreover, the electron beam was used to induce an - otherwise unstable - hot spot. Both investigations yielded information on the homogeneity of the samples. - An entirely new method of imaging the current distribution in superconducting interference devices

Systematic measurements of whole-body imaging dose distributions in image-guided radiation therapy

International Nuclear Information System (INIS)

Hälg, Roger A.; Besserer, Jürgen; Schneider, Uwe

2012-01-01

Purpose: The full benefit of the increased precision of contemporary treatment techniques can only be exploited if the accuracy of the patient positioning is guaranteed. Therefore, more and more imaging modalities are used in the process of the patient setup in clinical routine of radiation therapy. The improved accuracy in patient positioning, however, results in additional dose contributions to the integral patient dose. To quantify this, absorbed dose measurements from typical imaging procedures involved in an image-guided radiation therapy treatment were measured in an anthropomorphic phantom for a complete course of treatment. The experimental setup, including the measurement positions in the phantom, was exactly the same as in a preceding study of radiotherapy stray dose measurements. This allows a direct combination of imaging dose distributions with the therapy dose distribution. Methods: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from imaging devices used with treatment machines from the manufacturers Accuray, Elekta, Siemens, and Varian and from computed tomography scanners from GE Healthcare were determined and the resulting effective dose was calculated. The list of investigated imaging techniques consisted of cone beam computed tomography (kilo- and megavoltage), megavoltage fan beam computed tomography, kilo- and megavoltage planar imaging, planning computed tomography with and without gating methods and planar scout views. Results: A conventional 3D planning CT resulted in an effective dose additional to the treatment stray dose of less than 1 mSv outside of the treated volume, whereas a 4D planning CT resulted in a 10 times larger dose. For a daily setup of the patient with two planar kilovoltage images or with a fan beam CT at the TomoTherapy unit, an additional effective dose outside of the treated volume of less than 0.4 mSv and 1

Examining the Spatial Distribution of Law Enforcement Encounters among People Who Inject Drugs after Implementation of Mexico’s Drug Policy Reform

OpenAIRE

Gaines, Tommi L.; Beletsky, Leo; Arredondo, Jaime; Werb, Daniel; Rangel, Gudelia; Vera, Alicia; Brouwer, Kimberly

2014-01-01

In 2009, Mexico decriminalized the possession of small amounts of illicit drugs for personal use in order to refocus law enforcement resources on drug dealers and traffickers. This study examines the spatial distribution of law enforcement encounters reported by people who inject drugs (PWID) in Tijuana, Mexico to identify concentrated areas of policing activity after implementation of the new drug policy. Mapping the physical location of law enforcement encounters provided by PWID (n = 461) ...

Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

CERN Document Server

Prud'homme, Robert

2012-01-01

This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

Science.gov (United States)

Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

2017-12-11

Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

Science.gov (United States)

Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of User Distribution Image Size and Position of Each Observation Area of Meteorological Imager in COMS

Directory of Open Access Journals (Sweden)

Jeong-Soo Seo

2006-12-01

Full Text Available In this paper, requirements of Meteorological Administration about Meteorological Imager (MI of Communications, Ocean and Meteorological Satellite (COMS is analyzed for the design of COMS ground station and according to the analysis results, the distribution image size of each observation area suitable for satellite Field Of View (FOV stated at the requirements of meteorological administration is determined and the precise satellite FOV and the size of distribution image is calculated on the basis of the image size of the determined observation area. The results in this paper were applied to the detailed design for COMS ground station and also are expected to be used for the future observation scheduling and the scheduling of distribution of user data.

Distribution of Spiked Drugs between Milk Fat, Skim Milk, Whey, Curd, and Milk Protein Fractions: Expansion of Partitioning Models.

Science.gov (United States)

Lupton, Sara J; Shappell, Nancy W; Shelver, Weilin L; Hakk, Heldur

2018-01-10

The distributions of eight drugs (acetaminophen, acetylsalicylic acid/salicylic acid, ciprofloxacin, clarithromycin, flunixin, phenylbutazone, praziquantel, and thiamphenicol) were determined in milk products (skim milk, milk fat, curd, whey, and whey protein) and used to expand a previous model (from 7 drugs to 15 drugs) for predicting drug distribution. Phenylbutazone and praziquantel were found to distribute with the lipid and curd phases (≥50%). Flunixin distribution was lower but similar in direction (12% in milk fat, 39% in curd). Acetaminophen, ciprofloxacin, and praziquantel preferentially associated with casein proteins, whereas thiamphenicol and clarithromycin associated preferentially to whey proteins. Regression analyses for log [milk fat]/[skim milk] and log [curd]/[whey] had r 2 values of 0.63 and 0.67, respectively, with p of <0.001 for 15 drugs (7 previously tested and 8 currently tested). The robustness of the distribution model was enhanced by doubling the number of drugs originally tested.

Combination of MALDI-MSI and cassette dosing for evaluation of drug distribution in human skin explant

DEFF Research Database (Denmark)

Sørensen, Isabella S; Janfelt, Christian; Nielsen, Mette Marie B

2017-01-01

Study of skin penetration and distribution of the drug compounds in the skin is a major challenge in the development of topical drug products for treatment of skin diseases. It is crucial to have fast and efficacious screening methods which can provide information concerning the skin penetration ...... that combination of MALDI-MSI and cassette dosing can be used as a medium throughput screening tool at an early stage in the drug discovery/development process. Graphical abstract Investigation of drug distribution in human skin explant by MALDI-MSI after cassette dosing....

Radioactivity distribution measurement of various natural material surfaces with imaging plate

International Nuclear Information System (INIS)

Mori, C.; Suzuki, T.; Koido, S.; Uritani, A.; Yanagida, K.; Wu, Y.; Nishizawa, K.

1996-01-01

Distribution images of natural radioactivity in natural materials such as vegetables were obtained by using Imaging Platc. In ssuch cases, it is necessary to reduce background radiation intensity by one order or more. Graded shielding is very important. Espacially, the innermost surface of a shielding box sshould be covered with acrylic rein plate. We obtained natural radioactivity distribution images of vegetable, sea food, mea etc. Most β-rays emitted from 40 K print the radioactivity distribution image. Comparison between γ-ray intensity of KCL solution measured with HPGe detector and that of natural material specimen gave the radioactivity around 0.06- 0.04Bq/g depending on the kind and the part of specimens. (author). 6 refs., 5 figs., 1 tab

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

Directory of Open Access Journals (Sweden)

M. Thanou

2013-01-01

Full Text Available Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS- mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery.

An integrated drug prescription and distribution system: challenges and opportunities.

Science.gov (United States)

Lanssiers, R; Everaert, E; De Win, M; Van De Velde, R; De Clercq, H

2002-01-01

Using the hospital's drug prescription and distribution system as a guide, benefits and drawbacks of a medical activity management system that is tightly integrated with the supply chain management of a hospital will be discussed from the point of view of various participating healthcare actors.

Smart stimuli sensitive nanogels in cancer drug delivery and imaging: a review.

Science.gov (United States)

Maya, S; Sarmento, Bruno; Nair, Amrita; Rejinold, N Sanoj; Nair, Shantikumar V; Jayakumar, R

2013-01-01

Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload drugs within the nanogel matrix, the high stability in aqueous media, their stimuli responsively behavior potential, and the versatility in release drugs in a controlled manner make them very attractive for use in the area of drug delivery. The materials used for the preparation of nanogels ranged from natural polymers like ovalbumin, pullulan, hyaluronic acid, methacrylated chondroitin sulfate and chitosan, to synthetic polymers like poly (N-isopropylacrylamide), poly (Nisopropylacrylamide- co-acrylic acid) and poly (ethylene glycol)-b-poly (methacrylic acid). The porous nanogels have been finding application as anti-cancer drug and imaging agent reservoirs. Smart nanogels responding to external stimuli such as temperature, pH etc can be designed for diverse therapeutic and diagnostic applications. The nanogels have also been surface functionalized with specific ligands aiding in targeted drug delivery. This review focus on stimuli-sensitive, multi-responsive, magnetic and targeted nanogels providing a brief insight on the application of nanogels in cancer drug delivery and imaging in detail.

Counterfeiting in performance- and image-enhancing drugs.

Science.gov (United States)

Graham, Michael R; Ryan, Paul; Baker, Julien S; Davies, Bruce; Thomas, Non-Eleri; Cooper, Stephen-Mark; Evans, Peter; Easmon, Sue; Walker, Christopher J; Cowan, David; Kicman, Andrew T

2009-03-01

The current drastic escalation in obesity may be contributing to the exponential rise in drugs used for image enhancement. Drugs such as anabolic-androgenic steroids (AAS) are perceived as a viable method of achieving a perfect physique. They are also the most widely abused drugs in sport. The Internet has encouraged the abuse of expensive drugs, particularly human growth hormone (hGH), resulting in increased importation for personal use. The substantial increase in this market has opened up avenues for counterfeiting, estimated as a multi-million pound business. The acute adverse effects from contaminated vials may result in a variety of pathologies including communicable diseases. In 2007, in the UK, a series of intramuscular abscesses, requiring surgical treatment, led us to study samples obtained from the underground market. The analysis of 38 parenteral samples and 19 oral samples of tablets was performed by a World Anti-Doping Agency (WADA) accredited laboratory, in an attempt to establish the extent of available counterfeit products. Fifty-three per cent (20) of the injectable AAS esters and 21% (4) of the oral tablets were counterfeit. Culture and sensitivity revealed the presence of skin commensal organisms, which may have contributed to the development of the abscesses. Users of AAS and hGH for sport, including bodybuilding, are currently risking their health because of counterfeit and poorly controlled products. Copyright 2009 John Wiley & Sons, Ltd.

Cancer nanomedicine: from drug delivery to imaging.

Science.gov (United States)

Chow, Edward Kai-Hua; Ho, Dean

2013-12-18

Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.

Three dimensional multi perspective imaging with randomly distributed sensors

International Nuclear Information System (INIS)

DaneshPanah, Mehdi; Javidi, Bahrain

2008-01-01

In this paper, we review a three dimensional (3D) passive imaging system that exploits the visual information captured from the scene from multiple perspectives to reconstruct the scene voxel by voxel in 3D space. The primary contribution of this work is to provide a computational reconstruction scheme based on randomly distributed sensor locations in space. In virtually all of multi perspective techniques (e.g. integral imaging, synthetic aperture integral imaging, etc), there is an implicit assumption that the sensors lie on a simple, regular pickup grid. Here, we relax this assumption and suggest a computational reconstruction framework that unifies the available methods as its special cases. The importance of this work is that it enables three dimensional imaging technology to be implemented in a multitude of novel application domains such as 3D aerial imaging, collaborative imaging, long range 3D imaging and etc, where sustaining a regular pickup grid is not possible and/or the parallax requirements call for a irregular or sparse synthetic aperture mode. Although the sensors can be distributed in any random arrangement, we assume that the pickup position is measured at the time of capture of each elemental image. We demonstrate the feasibility of the methods proposed here by experimental results.

Spatiotemporal Quantification of Local Drug Delivery Using MRI

Science.gov (United States)

Giers, Morgan B.; McLaren, Alex C.; Plasencia, Jonathan D.; McLemore, Ryan; Caplan, Michael R.

2013-01-01

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery was performed to visualize and quantify the time resolved distribution of MRI contrast agents. Three-dimensional T 1 maps (generated from T 1-weighted images with varied T R) were processed using noise-reducing filtering. A segmented region of contrast, from a thresholded image, was converted to concentration maps using the equation 1/T 1 = 1/T 1,0 + R 1 C, where T 1,0 and T 1 are the precontrast and postcontrast T 1 map values, respectively. In this technique, a uniform estimated value for T 1,0 was used. Error estimations were performed for each step. The practical usefulness of this method was assessed using comparisons between devices located in different locations both with and without contrast. The method using a uniform T 1,0, requiring no registration of pre- and postcontrast image volumes, was compared to a method using either affine or deformation registrations. PMID:23710248

Childhood extracranial neoplasms: the role of imaging in drug development and clinical trials

International Nuclear Information System (INIS)

Fowkes, Lucy A.; Koh, Dow-Mu; MacVicar, David; Collins, David J.; Jerome, Neil P.; Chua, Sue C.; Pearson, Andrew D.J.

2015-01-01

Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed. (orig.)

Childhood extracranial neoplasms: the role of imaging in drug development and clinical trials

Energy Technology Data Exchange (ETDEWEB)

Fowkes, Lucy A.; Koh, Dow-Mu; MacVicar, David [Royal Marsden NHS Foundation Trust, Department of Radiology, Sutton, Surrey (United Kingdom); Collins, David J.; Jerome, Neil P. [Institute of Cancer Research, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Chua, Sue C. [Royal Marsden NHS Foundation Trust, Nuclear Medicine and PET Department, Sutton, Surrey (United Kingdom); Pearson, Andrew D.J. [Royal Marsden NHS Foundation Trust, Paediatric Drug Development Unit, Children and Young People' s Unit, Sutton, Surrey (United Kingdom)

2015-10-15

Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed. (orig.)

Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles.

NARCIS (Netherlands)

Fokong, S.; Theek, B.; Koczera, P.; Appold, L.; Resch-Genger, U.; van Zandvoort, M.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

2012-01-01

Abstract Microbubbles (MB) are routinely used contrast agents for functional and molecular ultrasound (US) imaging. In addition, they have been attracting more and more attention for drug delivery purposes, enabling e.g. US-mediated drug delivery across biological barriers and US-induced triggered

Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

Science.gov (United States)

Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

2017-04-01

Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

Science.gov (United States)

Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

2015-12-01

Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

Science.gov (United States)

Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

2013-01-01

High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

Image quality and dose distributions of three linac-based imaging modalities

Energy Technology Data Exchange (ETDEWEB)

Dzierma, Yvonne; Ames, Evemarie; Nuesken, Frank; Palm, Jan; Licht, Norbert; Ruebe, Christian [Universitaetsklinikum des Saarlandes, Klinik fuer Strahlentherapie und Radioonkologie, Homburg/Saar (Germany)

2015-04-01

Linac-based patient imaging is possible with a variety of techniques using different photon energies. The purpose of this work is to compare three imaging systems operating at 6 MV, flattening free filter (FFF) 1 MV, and 121 kV. The dose distributions of all pretreatment set-up images (over 1,000) were retrospectively calculated on the planning computed tomography (CT) images for all patients with prostate and head-and-neck cancer treated at our institution in 2013. We analyzed the dose distribution and the dose to organs at risk. For head-and-neck cancer patients, the imaging dose from 6-MV cone beam CT (CBCT) reached maximum values at around 8 cGy. The 1-MV CBCT dose was about 63-79 % of the 6-MV CBCT dose for all organs at risk. Planar imaging reduced the imaging dose from CBCT to 30-40 % for both megavoltage modalities. The dose from the kilovoltage CBCT was 4-10 % of the 6-MV CBCT dose. For prostate cancer patients, the maximum dose from 6-MV CBCT reached 13-15 cGy, and was reduced to 66-73 % for 1 MV. Planar imaging reduces the MV CBCT dose to 10-20 %. The kV CBCT dose is 15-20 % of the 6-MV CBCT dose, slightly higher than the dose from MV axes. The dose distributions differ markedly in response to the different beam profiles and dose-depth characteristics. (orig.) [German] Linac-basierte Bildgebung zur Patientenlagerung ist mit einer Vielzahl von Techniken unterschiedlicher Photonenenergien moeglich. Ziel dieser Arbeit ist der Vergleich dreier Bildgebungssysteme mit 6 MV (Megavolt), FFF 1 MV, und 121 kV (Kilovolt). Fuer alle im Jahr 2013 an unserer Klinik behandelten Prostata- und HNO-Patienten wurden retrospektiv die Dosisverteilungen aller Verifikationsaufnahmen (ueber 1000 insgesamt) auf der Planungs-Computertomographie (CT) berechnet. Wir analysierten die Dosisverteilung und die Dosis an den Risikoorganen. Bei HNO-Patienten erreichte die Dosis von 6 MV ''Cone-beam''-CT (CBCT)Maximalwerte um 8 cGy. Mit 1 MV wird die Dosis auf 63

An approach for quantification of platinum distribution in tissues by LA-ICP-MS imaging using isotope dilution analysis.

Science.gov (United States)

Moraleja, I; Mena, M L; Lázaro, A; Neumann, B; Tejedor, A; Jakubowski, N; Gómez-Gómez, M M; Esteban-Fernández, D

2018-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been revealed as a convenient technique for trace elemental imaging in tissue sections, providing elemental 2D distribution at a quantitative level. For quantification purposes, in the last years several approaches have been proposed in the literature such as the use of CRMs or matrix matched standards. The use of Isotope Dilution (ID) for quantification by LA-ICP-MS has been also described, being mainly useful for bulk analysis but not feasible for spatial measurements so far. In this work, a quantification method based on ID analysis was developed by printing isotope-enriched inks onto kidney slices from rats treated with antitumoral Pt-based drugs using a commercial ink-jet device, in order to perform an elemental quantification in different areas from bio-images. For the ID experiments 194 Pt enriched platinum was used. The methodology was validated by deposition of natural Pt standard droplets with a known amount of Pt onto the surface of a control tissue, where could be quantified even 50pg of Pt, with recoveries higher than 90%. The amount of Pt present in the whole kidney slices was quantified for cisplatin, carboplatin and oxaliplatin-treated rats. The results obtained were in accordance with those previously reported. The amount of Pt distributed between the medullar and cortical areas was also quantified, observing different behavior for the three drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Feasibility of abdominal plain film images in evaluation suspected drug smuggler

International Nuclear Information System (INIS)

Sormaala, Markus J.; Salonen, Hanna-Mari; Mattila, Ville M.; Kivisaari, Arto; Autti, Taina

2012-01-01

Objective: Drug smuggling in the gastrointestinal tract has soared within the last 20 years. Though illegal substances in the gastrointestinal tract can be visualized with ultrasound, MRI and CT, the abdominal radiograph has by far remained the most frequently used way of detecting smuggled drugs. The purpose of the study was to evaluate the inter-radiologist interpretation error and the reliability of the abdominal radiograph in detecting smuggled drugs. Materials and methods: A total of 279 abdominal radiographs of suspected smugglers were classified by three radiologists as clearly positive or negative for drug smuggling. All available information about the cases was collected from the customs officers and police. Results: Out of these cases 203 (73%) were interpreted as negative and 35 (13%) as positive by all three radiologists. In 86% of the cases there was, therefore, an inter-radiological agreement in interpreting the images. In 41 (14%) cases, however, there was an inter-radiologist disagreement. Kappa-value for inter-observer variability was 0.70. Conclusions: In up to a seventh of the abdominal radiographs the interpretation can be challenging even for an experienced radiologist. False positive interpretation can lead to innocent passengers being detained in vain. As negatively interpreted images usually result in releasing of the suspect, there is no way of knowing how many false negative occur. This makes the abdominal radiograph a suboptimal examination, and low dose CT should be considered as the screening modality for gastrointestinal drug smugglers

Feasibility of abdominal plain film images in evaluation suspected drug smuggler

Energy Technology Data Exchange (ETDEWEB)

Sormaala, Markus J., E-mail: markus.sormaala@welho.com [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Salonen, Hanna-Mari, E-mail: hanna-mari.salonen@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Mattila, Ville M., E-mail: ville.mattila@uta.fi [Department of Orthopedic Surgery and Trauma, Tampere University Hospital, Tampere (Finland); Kivisaari, Arto, E-mail: arto.kivisaari@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Autti, Taina, E-mail: taina.autti@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland)

2012-09-15

Objective: Drug smuggling in the gastrointestinal tract has soared within the last 20 years. Though illegal substances in the gastrointestinal tract can be visualized with ultrasound, MRI and CT, the abdominal radiograph has by far remained the most frequently used way of detecting smuggled drugs. The purpose of the study was to evaluate the inter-radiologist interpretation error and the reliability of the abdominal radiograph in detecting smuggled drugs. Materials and methods: A total of 279 abdominal radiographs of suspected smugglers were classified by three radiologists as clearly positive or negative for drug smuggling. All available information about the cases was collected from the customs officers and police. Results: Out of these cases 203 (73%) were interpreted as negative and 35 (13%) as positive by all three radiologists. In 86% of the cases there was, therefore, an inter-radiological agreement in interpreting the images. In 41 (14%) cases, however, there was an inter-radiologist disagreement. Kappa-value for inter-observer variability was 0.70. Conclusions: In up to a seventh of the abdominal radiographs the interpretation can be challenging even for an experienced radiologist. False positive interpretation can lead to innocent passengers being detained in vain. As negatively interpreted images usually result in releasing of the suspect, there is no way of knowing how many false negative occur. This makes the abdominal radiograph a suboptimal examination, and low dose CT should be considered as the screening modality for gastrointestinal drug smugglers.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

Science.gov (United States)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in

Model-based VQ for image data archival, retrieval and distribution

Science.gov (United States)

Manohar, Mareboyana; Tilton, James C.

1995-01-01

An ideal image compression technique for image data archival, retrieval and distribution would be one with the asymmetrical computational requirements of Vector Quantization (VQ), but without the complications arising from VQ codebooks. Codebook generation and maintenance are stumbling blocks which have limited the use of VQ as a practical image compression algorithm. Model-based VQ (MVQ), a variant of VQ described here, has the computational properties of VQ but does not require explicit codebooks. The codebooks are internally generated using mean removed error and Human Visual System (HVS) models. The error model assumed is the Laplacian distribution with mean, lambda-computed from a sample of the input image. A Laplacian distribution with mean, lambda, is generated with uniform random number generator. These random numbers are grouped into vectors. These vectors are further conditioned to make them perceptually meaningful by filtering the DCT coefficients from each vector. The DCT coefficients are filtered by multiplying by a weight matrix that is found to be optimal for human perception. The inverse DCT is performed to produce the conditioned vectors for the codebook. The only image dependent parameter used in the generation of codebook is the mean, lambda, that is included in the coded file to repeat the codebook generation process for decoding.

[Drug vectorization or how to modulate tissular and cellular distribution of biologically active compounds].

Science.gov (United States)

Couvreur, P

2001-07-01

Drug vectorization has undergone considerable development over the last few years. This review focuses on the intravenous route of administration. Colloid formulations allow a modulation of drug tissue distribution. Using liposomes and nanoparticles with unmodified surfaces, drugs can be targeted to macrophages of the reticulum endothelium system. When the liposomes or nanoparticles are covered with hydrophilic or flexible polymers, the vascular phase can be favored in order, for example, to facilitate selective extravasation at a tumor site. Therapeutic applications of these systems are presented. The development of "intelligent" vectors capable of modulating intracellular distribution of an active compounds is an equally interesting approach, for example pH-sensitive liposomes or nanoparticles decorated with folic acid capable of targeting intracellular cytoplasm.

Information system for administrating and distributing color images through internet

Directory of Open Access Journals (Sweden)

2007-01-01

Full Text Available The information system for administrating and distributing color images through the Internet ensures the consistent replication of color images, their storage - in an on-line data base - and predictable distribution, by means of a digitally distributed flow, based on Windows platform and POD (Print On Demand technology. The consistent replication of color images inde-pendently from the parameters of the processing equipment and from the features of the programs composing the technological flow, is ensured by the standard color management sys-tem defined by ICC (International Color Consortium, which is integrated by the Windows operation system and by the POD technology. The latter minimize the noticeable differences between the colors captured, displayed or printed by various replication equipments and/or edited by various graphical applications. The system integrated web application ensures the uploading of the color images in an on-line database and their administration and distribution among the users via the Internet. For the preservation of the data expressed by the color im-ages during their transfer along a digitally distributed flow, the software application includes an original tool ensuring the accurate replication of colors on computer displays or when printing them by means of various color printers or presses. For development and use, this application employs a hardware platform based on PC support and a competitive software platform, based on: the Windows operation system, the .NET. Development medium and the C# programming language. This information system is beneficial for creators and users of color images, the success of the printed or on-line (Internet publications depending on the sizeable, predictable and accurate replication of colors employed for the visual expression of information in every activity fields of the modern society. The herein introduced information system enables all interested persons to access the

Automatic Image Segmentation Using Active Contours with Univariate Marginal Distribution

Directory of Open Access Journals (Sweden)

I. Cruz-Aceves

2013-01-01

Full Text Available This paper presents a novel automatic image segmentation method based on the theory of active contour models and estimation of distribution algorithms. The proposed method uses the univariate marginal distribution model to infer statistical dependencies between the control points on different active contours. These contours have been generated through an alignment process of reference shape priors, in order to increase the exploration and exploitation capabilities regarding different interactive segmentation techniques. This proposed method is applied in the segmentation of the hollow core in microscopic images of photonic crystal fibers and it is also used to segment the human heart and ventricular areas from datasets of computed tomography and magnetic resonance images, respectively. Moreover, to evaluate the performance of the medical image segmentations compared to regions outlined by experts, a set of similarity measures has been adopted. The experimental results suggest that the proposed image segmentation method outperforms the traditional active contour model and the interactive Tseng method in terms of segmentation accuracy and stability.

Hybrid protein-inorganic nanoparticles: From tumor-targeted drug delivery to cancer imaging.

Science.gov (United States)

Elzoghby, Ahmed O; Hemasa, Ayman L; Freag, May S

2016-12-10

Recently, a great interest has been paid to the development of hybrid protein-inorganic nanoparticles (NPs) for drug delivery and cancer diagnostics in order to combine the merits of both inorganic and protein nanocarriers. This review primarily discusses the most outstanding advances in the applications of the hybrids of naturally-occurring proteins with iron oxide, gadolinium, gold, silica, calcium phosphate NPs, carbon nanotubes, and quantum dots in drug delivery and cancer imaging. Various strategies that have been utilized for the preparation of protein-functionalized inorganic NPs and the mechanisms involved in the drug loading process are discussed. How can the protein functionalization overcome the limitations of colloidal stability, poor dispersibility and toxicity associated with inorganic NPs is also investigated. Moreover, issues relating to the influence of protein hybridization on the cellular uptake, tumor targeting efficiency, systemic circulation, mucosal penetration and skin permeation of inorganic NPs are highlighted. A special emphasis is devoted to the novel approaches utilizing the protein-inorganic nanohybrids in combined cancer therapy, tumor imaging, and theranostic applications as well as stimuli-responsive drug release from the nanohybrids. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative analysis of drug distribution by ambient mass spectrometry imaging method with signal extinction normalization strategy and inkjet-printing technology.

Science.gov (United States)

Luo, Zhigang; He, Jingjing; He, Jiuming; Huang, Lan; Song, Xiaowei; Li, Xin; Abliz, Zeper

2018-03-01

Quantitative mass spectrometry imaging (MSI) is a robust approach that provides both quantitative and spatial information for drug candidates' research. However, because of complicated signal suppression and interference, acquiring accurate quantitative information from MSI data remains a challenge, especially for whole-body tissue sample. Ambient MSI techniques using spray-based ionization appear to be ideal for pharmaceutical quantitative MSI analysis. However, it is more challenging, as it involves almost no sample preparation and is more susceptible to ion suppression/enhancement. Herein, based on our developed air flow-assisted desorption electrospray ionization (AFADESI)-MSI technology, an ambient quantitative MSI method was introduced by integrating inkjet-printing technology with normalization of the signal extinction coefficient (SEC) using the target compound itself. The method utilized a single calibration curve to quantify multiple tissue types. Basic blue 7 and an antitumor drug candidate (S-(+)-deoxytylophorinidine, CAT) were chosen to initially validate the feasibility and reliability of the quantitative MSI method. Rat tissue sections (heart, kidney, and brain) administered with CAT was then analyzed. The quantitative MSI analysis results were cross-validated by LC-MS/MS analysis data of the same tissues. The consistency suggests that the approach is able to fast obtain the quantitative MSI data without introducing interference into the in-situ environment of the tissue sample, and is potential to provide a high-throughput, economical and reliable approach for drug discovery and development. Copyright © 2017 Elsevier B.V. All rights reserved.

High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

Directory of Open Access Journals (Sweden)

Cervantes Serena

2009-06-01

Full Text Available Abstract Background Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes. Results After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells. Conclusion This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.

Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery.

Science.gov (United States)

Xu, Huan; Cheng, Liang; Wang, Chao; Ma, Xinxing; Li, Yonggang; Liu, Zhuang

2011-12-01

Multimodal imaging and imaging-guided therapies have become a new trend in the current development of cancer theranostics. In this work, we encapsulate hydrophobic upconversion nanoparticles (UCNPs) together with iron oxide nanoparticles (IONPs) by using an amphiphilic block copolymer, poly (styrene-block-allyl alcohol) (PS(16)-b-PAA(10)), via a microemulsion method, obtaining an UC-IO@Polymer multi-functional nanocomposite system. Fluorescent dye and anti-cancer drug molecules can be further loaded inside the UC-IO@Polymer nanocomposite for additional functionalities. Utilizing the Squaraine (SQ) dye loaded nanocomposite (UC-IO@Polymer-SQ), triple-modal upconversion luminescence (UCL)/down-conversion fluorescence (FL)/magnetic resonance (MR) imaging is demonstrated in vitro and in vivo, and also applied for in vivo cancer cell tracking in mice. On the other hand, a chemotherapy drug, doxorubicin, is also loaded into the nanocomposite, forming an UC-IO@Polymer-DOX complex, which enables novel imaging-guided and magnetic targeted drug delivery. Our work provides a method to fabricate a nanocomposite system with highly integrated functionalities for multimodal biomedical imaging and cancer therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Distributed deep learning networks among institutions for medical imaging.

Science.gov (United States)

Chang, Ken; Balachandar, Niranjan; Lam, Carson; Yi, Darvin; Brown, James; Beers, Andrew; Rosen, Bruce; Rubin, Daniel L; Kalpathy-Cramer, Jayashree

2018-03-29

Deep learning has become a promising approach for automated support for clinical diagnosis. When medical data samples are limited, collaboration among multiple institutions is necessary to achieve high algorithm performance. However, sharing patient data often has limitations due to technical, legal, or ethical concerns. In this study, we propose methods of distributing deep learning models as an attractive alternative to sharing patient data. We simulate the distribution of deep learning models across 4 institutions using various training heuristics and compare the results with a deep learning model trained on centrally hosted patient data. The training heuristics investigated include ensembling single institution models, single weight transfer, and cyclical weight transfer. We evaluated these approaches for image classification in 3 independent image collections (retinal fundus photos, mammography, and ImageNet). We find that cyclical weight transfer resulted in a performance that was comparable to that of centrally hosted patient data. We also found that there is an improvement in the performance of cyclical weight transfer heuristic with a high frequency of weight transfer. We show that distributing deep learning models is an effective alternative to sharing patient data. This finding has implications for any collaborative deep learning study.

Magnetoacoustic microscopic imaging of conductive objects and nanoparticles distribution

Science.gov (United States)

Liu, Siyu; Zhang, Ruochong; Luo, Yunqi; Zheng, Yuanjin

2017-09-01

Magnetoacoustic tomography has been demonstrated as a powerful and low-cost multi-wave imaging modality. However, due to limited spatial resolution and detection efficiency of magnetoacoustic signal, full potential of the magnetoacoustic imaging remains to be tapped. Here we report a high-resolution magnetoacoustic microscopy method, where magnetic stimulation is provided by a compact solenoid resonance coil connected with a matching network, and acoustic reception is realized by using a high-frequency focused ultrasound transducer. Scanning the magnetoacoustic microscopy system perpendicularly to the acoustic axis of the focused transducer would generate a two-dimensional microscopic image with acoustically determined lateral resolution. It is analyzed theoretically and demonstrated experimentally that magnetoacoustic generation in this microscopic system depends on the conductivity profile of conductive objects and localized distribution of superparamagnetic iron magnetic nanoparticles, based on two different but related implementations. The lateral resolution is characterized. Directional nature of magnetoacoustic vibration and imaging sensitivity for mapping magnetic nanoparticles are also discussed. The proposed microscopy system offers a high-resolution method that could potentially map intrinsic conductivity distribution in biological tissue and extraneous magnetic nanoparticles.

Residual stress distribution analysis of heat treated APS TBC using image based modelling.

Science.gov (United States)

Li, Chun; Zhang, Xun; Chen, Ying; Carr, James; Jacques, Simon; Behnsen, Julia; di Michiel, Marco; Xiao, Ping; Cernik, Robert

2017-08-01

We carried out a residual stress distribution analysis in a APS TBC throughout the depth of the coatings. The samples were heat treated at 1150 °C for 190 h and the data analysis used image based modelling based on the real 3D images measured by Computed Tomography (CT). The stress distribution in several 2D slices from the 3D model is included in this paper as well as the stress distribution along several paths shown on the slices. Our analysis can explain the occurrence of the "jump" features near the interface between the top coat and the bond coat. These features in the residual stress distribution trend were measured (as a function of depth) by high-energy synchrotron XRD (as shown in our related research article entitled 'Understanding the Residual Stress Distribution through the Thickness of Atmosphere Plasma Sprayed (APS) Thermal Barrier Coatings (TBCs) by high energy Synchrotron XRD; Digital Image Correlation (DIC) and Image Based Modelling') (Li et al., 2017) [1].

Layered gadolinium hydroxides for simultaneous drug delivery and imaging.

Science.gov (United States)

Xu, Yadong; Goyanes, Alvaro; Wang, Yuwei; Weston, Andrew J; So, Po-Wah; Geraldes, Carlos F G C; Fogg, Andrew M; Basit, Abdul W; Williams, Gareth R

2018-02-27

The potential of the layered gadolinium hydroxide (LGdH) [Gd 2 (OH) 5 ]Cl·yH 2 O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion exchange intercalation, coprecipitation, and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR spectroscopy confirmed successful incorporation of the drug into the interlayer spaces of the LGdH in all cases. From a comparison of the guest anion sizes and interlayer spacings, the active ingredients are believed to adopt intertwined bilayer configurations between the LGdH layers. The materials prepared by coprecipitation in general have noticeably higher drug loadings than those produced by ion exchange or self-assembly, as a result of the incorporation of some neutral drug into the composites. The LGdH-drug intercalates are stable at neutral pH, but rapidly degrade in acidic conditions to free Gd 3+ into solution. While LGdH-nap releases its drug loading into solution very rapidly (within ca. 1.5 h) at pH 7.4, LGdH-dic shows sustained release over 4 h, and LGdH-ibu extends this to 24 h. The latter composites therefore can be incorporated into enteric-coated tablets to provide sustained release in the small intestine. The drug intercalates are highly biocompatible and retain the proton relaxivity properties of the parent LGdH-Cl, with the materials most promising for use as negative contrast agents in MRI. Overall, the LGdH-drug intercalation compounds appear to have great potential for use in theranostic applications.

MALDI-MS Imaging Analysis of Fungicide Residue Distributions on Wheat Leaf Surfaces.

Science.gov (United States)

Annangudi, Suresh P; Myung, Kyung; Avila Adame, Cruz; Gilbert, Jeffrey R

2015-05-05

Improved retention and distribution of agrochemicals on plant surfaces is an important attribute in the biological activity of pesticide. Although retention of agrochemicals on plants after spray application can be quantified using traditional analytical techniques including LC or GC, the spatial distribution of agrochemicals on the plants surfaces has received little attention. Matrix assisted laser desorption/ionization (MALDI) imaging technology has been widely used to determine the distribution of proteins, peptides and metabolites in different tissue sections, but its application to environmental research has been limited. Herein, we probed the potential utility of MALDI imaging in characterizing the distribution of three commercial fungicides on wheat leaf surfaces. Using this MALDI imaging method, we were able to detect 500 ng of epoxiconazole, azoxystrobin, and pyraclostrobin applied in 1 μL drop on the leaf surfaces using MALDI-MS. Subsequent dilutions of pyraclostrobin revealed that the compound can be chemically imaged on the leaf surfaces at levels as low as 60 ng of total applied in the area of 1 μL droplet. After application of epoxiconazole, azoxystrobin, and pyraclostrobin at a field rate of 100 gai/ha in 200 L water using a track sprayer system, residues of these fungicides on the leaf surfaces were sufficiently visualized. These results suggest that MALDI imaging can be used to monitor spatial distribution of agrochemicals on leaf samples after pesticide application.

Method of imaging the electrical conductivity distribution of a subsurface

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Johnson, Timothy C.

2017-09-26

A method of imaging electrical conductivity distribution of a subsurface containing metallic structures with known locations and dimensions is disclosed. Current is injected into the subsurface to measure electrical potentials using multiple sets of electrodes, thus generating electrical resistivity tomography measurements. A numeric code is applied to simulate the measured potentials in the presence of the metallic structures. An inversion code is applied that utilizes the electrical resistivity tomography measurements and the simulated measured potentials to image the subsurface electrical conductivity distribution and remove effects of the subsurface metallic structures with known locations and dimensions.

Distributed data collection for a database of radiological image interpretations

Science.gov (United States)

Long, L. Rodney; Ostchega, Yechiam; Goh, Gin-Hua; Thoma, George R.

1997-01-01

The National Library of Medicine, in collaboration with the National Center for Health Statistics and the National Institute for Arthritis and Musculoskeletal and Skin Diseases, has built a system for collecting radiological interpretations for a large set of x-ray images acquired as part of the data gathered in the second National Health and Nutrition Examination Survey. This system is capable of delivering across the Internet 5- and 10-megabyte x-ray images to Sun workstations equipped with X Window based 2048 X 2560 image displays, for the purpose of having these images interpreted for the degree of presence of particular osteoarthritic conditions in the cervical and lumbar spines. The collected interpretations can then be stored in a database at the National Library of Medicine, under control of the Illustra DBMS. This system is a client/server database application which integrates (1) distributed server processing of client requests, (2) a customized image transmission method for faster Internet data delivery, (3) distributed client workstations with high resolution displays, image processing functions and an on-line digital atlas, and (4) relational database management of the collected data.

Low-Complexity Compression Algorithm for Hyperspectral Images Based on Distributed Source Coding

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Yongjian Nian

2013-01-01

Full Text Available A low-complexity compression algorithm for hyperspectral images based on distributed source coding (DSC is proposed in this paper. The proposed distributed compression algorithm can realize both lossless and lossy compression, which is implemented by performing scalar quantization strategy on the original hyperspectral images followed by distributed lossless compression. Multilinear regression model is introduced for distributed lossless compression in order to improve the quality of side information. Optimal quantized step is determined according to the restriction of the correct DSC decoding, which makes the proposed algorithm achieve near lossless compression. Moreover, an effective rate distortion algorithm is introduced for the proposed algorithm to achieve low bit rate. Experimental results show that the compression performance of the proposed algorithm is competitive with that of the state-of-the-art compression algorithms for hyperspectral images.

Phase distribution measurements in narrow rectangular channels using image processing techniques

International Nuclear Information System (INIS)

Bentley, C.; Ruggles, A.

1991-01-01

Many high flux research reactor fuel assemblies are cooled by systems of parallel narrow rectangular channels. The HFIR is cooled by single phase forced convection under normal operating conditions. However, two-phase forced convection or two phase mixed convection can occur in the fueled region as a result of some hypothetical accidents. Such flow conditions would occur only at decay power levels. The system pressure would be around 0.15 MPa in such circumstances. Phase distribution of air-water flow in a narrow rectangular channel is examined using image processing techniques. Ink is added to the water and clear channel walls are used to allow high speed still photographs and video tape to be taken of the air-water flow field. Flow field images are digitized and stored in a Macintosh 2ci computer using a frame grabber board. Local grey levels are related to liquid thickness in the flow channel using a calibration fixture. Image processing shareware is used to calculate the spatially averaged liquid thickness from the image of the flow field. Time averaged spatial liquid distributions are calculated using image calculation algorithms. The spatially averaged liquid distribution is calculated from the time averaged spatial liquid distribution to formulate the combined temporally and spatially averaged fraction values. The temporally and spatially averaged liquid fractions measured using this technique compare well to those predicted from pressure gradient measurements at zero superficial liquid velocity

Distribution of normal superficial ocular vessels in digital images.

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Banaee, Touka; Ehsaei, Asieh; Pourreza, Hamidreza; Khajedaluee, Mohammad; Abrishami, Mojtaba; Basiri, Mohsen; Daneshvar Kakhki, Ramin; Pourreza, Reza

2014-02-01

To investigate the distribution of different-sized vessels in the digital images of the ocular surface, an endeavor which may provide useful information for future studies. This study included 295 healthy individuals. From each participant, four digital photographs of the superior and inferior conjunctivae of both eyes, with a fixed succession of photography (right upper, right lower, left upper, left lower), were taken with a slit lamp mounted camera. Photographs were then analyzed by a previously described algorithm for vessel detection in the digital images. The area (of the image) occupied by vessels (AOV) of different sizes was measured. Height, weight, fasting blood sugar (FBS) and hemoglobin levels were also measured and the relationship between these parameters and the AOV was investigated. These findings indicated a statistically significant difference in the distribution of the AOV among the four conjunctival areas. No significant correlations were noted between the AOV of each conjunctival area and the different demographic and biometric factors. Medium-sized vessels were the most abundant vessels in the photographs of the four investigated conjunctival areas. The AOV of the different sizes of vessels follows a normal distribution curve in the four areas of the conjunctiva. The distribution of the vessels in successive photographs changes in a specific manner, with the mean AOV becoming larger as the photos were taken from the right upper to the left lower area. The AOV of vessel sizes has a normal distribution curve and medium-sized vessels occupy the largest area of the photograph. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

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Kaur, Randeep; Badea, Ildiko

2013-01-01

Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.

Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions

Science.gov (United States)

Sharifzadeh, Mohsen; Bernstein, Paul S.; Gellermann, Werner

2006-10-01

We have developed a CCD-camera-based nonmydriatic instrument that detects fluorescence from retinal lipofuscin chromophores ("autofluorescence") as a means to indirectly quantify and spatially image the distribution of macular pigment (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations containing MP, since MP has a competing absorption in the blue-green wavelength region. Projecting a large diameter, 488 nm excitation spot onto the retina, centered on the fovea, but extending into the macular periphery, and comparing lipofuscin fluorescence intensities outside and inside the foveal area, it is possible to spatially map out the distribution of MP. Spectrally selective detection of the lipofuscin fluorescence reveals an important wavelength dependence of the obtainable image contrast and deduced MP optical density levels, showing that it is important to block out interfering fluorescence contributions in the detection setup originating from ocular media such as the lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies, we find widely varying spatial extent of MP, distinctly differing distribution patterns of MP, and strongly differing absolute MP levels among individuals. Our population study suggests that MP imaging based on lipofuscin fluorescence is useful as a relatively simple, objective, and quantitative noninvasive optical technique suitable to rapidly screen MP levels and distributions in healthy humans with undilated pupils.

A three-dimensional dose-distribution estimation system using computerized image reconstruction

International Nuclear Information System (INIS)

Nishijima, Akihiko; Kidoya, Eiji; Komuro, Hiroyuki; Tanaka, Masato; Asada, Naoki.

1990-01-01

In radiotherapy planning, three dimensional (3-D) estimation of dose distribution has been very troublesome and time-consuming. To solve this problem, a simple and fast 3-D dose distribution image using a computer and Charged Couple Device (CCD) camera was developed. A series of X-ray films inserted in the phantom using a linear accelerator unit was exposed. The degree of film density was degitized with a CCD camera and a minicomputer (VAX 11-750). After that these results were compared with the present depth dose obtained by a JARP type dosimeter, with a dose error being less than 2%. The 3-D dose distribution image could accurately depict the density changes created by aluminum and air put into the phantom. The contrast resolution of the CCD camera seemed to be superior to the convention densitometer in the low-to-intermediate contrast range. In conclusion, our method seem to be very fast and simple for obtaining 3-D dose distribution images and is very effective when compared with the conventional method. (author)

Identification and verification of critical performance dimensions. Phase 1 of the systematic process redesign of drug distribution.

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Colen, Hadewig B; Neef, Cees; Schuring, Roel W

2003-06-01

Worldwide patient safety has become a major social policy problem for healthcare organisations. As in other organisations, the patients in our hospital also suffer from an inadequate distribution process, as becomes clear from incident reports involving medication errors. Medisch Spectrum Twente is a top primary-care, clinical, teaching hospital. The hospital pharmacy takes care of 1070 internal beds and 1120 beds in an affiliated psychiatric hospital and nursing homes. In the beginning of 1999, our pharmacy group started a large interdisciplinary research project to develop a safe, effective and efficient drug distribution system by using systematic process redesign. The process redesign includes both organisational and technological components. This article describes the identification and verification of critical performance dimensions for the design of drug distribution processes in hospitals (phase 1 of the systematic process redesign of drug distribution). Based on reported errors and related causes, we suggested six generic performance domains. To assess the role of the performance dimensions, we used three approaches: flowcharts, interviews with stakeholders and review of the existing performance using time studies and medication error studies. We were able to set targets for costs, quality of information, responsiveness, employee satisfaction, and degree of innovation. We still have to establish what drug distribution system, in respect of quality and cost-effectiveness, represents the best and most cost-effective way of preventing medication errors. We intend to develop an evaluation model, using the critical performance dimensions as a starting point. This model can be used as a simulation template to compare different drug distribution concepts in order to define the differences in quality and cost-effectiveness.

The pivotal role of multimodality reporter sensors in drug discovery: from cell based assays to real time molecular imaging.

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Ray, Pritha

2011-04-01

Development and marketing of new drugs require stringent validation that are expensive and time consuming. Non-invasive multimodality molecular imaging using reporter genes holds great potential to expedite these processes at reduced cost. New generations of smarter molecular imaging strategies such as Split reporter, Bioluminescence resonance energy transfer, Multimodality fusion reporter technologies will further assist to streamline and shorten the drug discovery and developmental process. This review illustrates the importance and potential of molecular imaging using multimodality reporter genes in drug development at preclinical phases.

Distributed Storage Algorithm for Geospatial Image Data Based on Data Access Patterns.

Directory of Open Access Journals (Sweden)

Shaoming Pan

Full Text Available Declustering techniques are widely used in distributed environments to reduce query response time through parallel I/O by splitting large files into several small blocks and then distributing those blocks among multiple storage nodes. Unfortunately, however, many small geospatial image data files cannot be further split for distributed storage. In this paper, we propose a complete theoretical system for the distributed storage of small geospatial image data files based on mining the access patterns of geospatial image data using their historical access log information. First, an algorithm is developed to construct an access correlation matrix based on the analysis of the log information, which reveals the patterns of access to the geospatial image data. Then, a practical heuristic algorithm is developed to determine a reasonable solution based on the access correlation matrix. Finally, a number of comparative experiments are presented, demonstrating that our algorithm displays a higher total parallel access probability than those of other algorithms by approximately 10-15% and that the performance can be further improved by more than 20% by simultaneously applying a copy storage strategy. These experiments show that the algorithm can be applied in distributed environments to help realize parallel I/O and thereby improve system performance.

Distributed Storage Algorithm for Geospatial Image Data Based on Data Access Patterns.

Science.gov (United States)

Pan, Shaoming; Li, Yongkai; Xu, Zhengquan; Chong, Yanwen

2015-01-01

Declustering techniques are widely used in distributed environments to reduce query response time through parallel I/O by splitting large files into several small blocks and then distributing those blocks among multiple storage nodes. Unfortunately, however, many small geospatial image data files cannot be further split for distributed storage. In this paper, we propose a complete theoretical system for the distributed storage of small geospatial image data files based on mining the access patterns of geospatial image data using their historical access log information. First, an algorithm is developed to construct an access correlation matrix based on the analysis of the log information, which reveals the patterns of access to the geospatial image data. Then, a practical heuristic algorithm is developed to determine a reasonable solution based on the access correlation matrix. Finally, a number of comparative experiments are presented, demonstrating that our algorithm displays a higher total parallel access probability than those of other algorithms by approximately 10-15% and that the performance can be further improved by more than 20% by simultaneously applying a copy storage strategy. These experiments show that the algorithm can be applied in distributed environments to help realize parallel I/O and thereby improve system performance.

Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

Directory of Open Access Journals (Sweden)

Kaur R

2013-01-01

Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering

3-D Image Analysis of Fluorescent Drug Binding

Directory of Open Access Journals (Sweden)

M. Raquel Miquel

2005-01-01

Full Text Available Fluorescent ligands provide the means of studying receptors in whole tissues using confocal laser scanning microscopy and have advantages over antibody- or non-fluorescence-based method. Confocal microscopy provides large volumes of images to be measured. Histogram analysis of 3-D image volumes is proposed as a method of graphically displaying large amounts of volumetric image data to be quickly analyzed and compared. The fluorescent ligand BODIPY FL-prazosin (QAPB was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor binding under different conditions and the technique is sensitive enough to detect changes in receptor availability after antagonist incubation or genetic manipulations. QAPB binding was concentration dependent, causing concentration-related rightward shifts in the histogram. In the presence of 10 μM phenoxybenzamine (blocking agent, the QAPB (50 nM histogram overlaps the autofluorescence curve. The histogram obtained for the 1D knockout aorta lay to the left of that of control and 1B knockout aorta, indicating a reduction in 1D receptors. We have shown, for the first time, that it is possible to graphically display binding of a fluorescent drug to a biological tissue. Although our application is specific to adrenergic receptors, the general method could be applied to any volumetric, fluorescence-image-based assay.

Real-time dynamic imaging of virus distribution in vivo.

Directory of Open Access Journals (Sweden)

Sean E Hofherr

2011-02-01

Full Text Available The distribution of viruses and gene therapy vectors is difficult to assess in a living organism. For instance, trafficking in murine models can usually only be assessed after sacrificing the animal for tissue sectioning or extraction. These assays are laborious requiring whole animal sectioning to ascertain tissue localization. They also obviate the ability to perform longitudinal or kinetic studies in one animal. To track viruses after systemic infection, we have labeled adenoviruses with a near-infrared (NIR fluorophore and imaged these after intravenous injection in mice. Imaging was able to track and quantitate virus particles entering the jugular vein simultaneous with injection, appearing in the heart within 500 milliseconds, distributing in the bloodstream and throughout the animal within 7 seconds, and that the bulk of virus distribution was essentially complete within 3 minutes. These data provide the first in vivo real-time tracking of the rapid initial events of systemic virus infection.

IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer.

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Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

2016-04-17

Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

Science.gov (United States)

Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

2016-05-01

Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

Imaging drugs with and without clinical analgesic efficacy.

Science.gov (United States)

Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

2011-12-01

The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with μ-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK(1) receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts.

Estimation of four-dimensional dose distribution using electronic portal imaging device in radiation therapy

International Nuclear Information System (INIS)

Mizoguchi, Asumi; Arimura, Hidetaka; Shioyama, Yoshiyuki

2013-01-01

We are developing a method to evaluate four-dimensional radiation dose distribution in a patient body based upon the animated image of EPID (electronic portal imaging device) which is an image of beam-direction at the irradiation. In the first place, we have obtained the image of the dose which is emitted from patient body at therapy planning using therapy planning CT image and dose evaluation algorism. In the second place, we have estimated the emission dose image at the irradiation using EPID animated image which is obtained at the irradiation. In the third place, we have got an affine transformation matrix including respiratory movement in the body by performing linear registration on the emission dose image at therapy planning to get the one at the irradiation. In the fourth place, we have applied the affine transformation matrix on the therapy planning CT image and estimated the CT image 'at irradiation'. Finally we have evaluated four-dimensional dose distribution by calculating dose distribution in the CT image 'at irradiation' which has been estimated for each frame of the EPID animated-image. This scheme may be useful for evaluating therapy results and risk management. (author)

Influence of barium sulfate X-ray imaging contrast material on properties of floating drug delivery tablets.

Science.gov (United States)

Diós, Péter; Szigeti, Krisztián; Budán, Ferenc; Pócsik, Márta; Veres, Dániel S; Máthé, Domokos; Pál, Szilárd; Dévay, Attila; Nagy, Sándor

2016-12-01

The objective of the study was to reveal the influence of necessarily added barium sulfate (BaSO 4 ) X-ray contrast material on floating drug delivery tablets. Based on literature survey, a chosen floating tablet composition was determined containing HPMC and carbopol 943P as matrix polymers. One-factor factorial design with five levels was created for evaluation of BaSO 4 (X 1 ) effects on experimental parameters of tablets including: floating lag time, total floating time, swelling-, erosion-, dissolution-, release kinetics parameters and X-ray detected volume changes of tablets. Applied concentrations of BaSO 4 were between 0 and 20.0% resulting in remarkable alteration of experimental parameters related especially to flotation. Drastic deterioration of floating lag time and total floating time could be observed above 15.0% BaSO 4 . Furthermore, BaSO 4 showed to increase the integrity of tablet matrix by reducing eroding properties. A novel evaluation of dissolutions from floating drug delivery systems was introduced, which could assess the quantity of drug dissolved from dosage form in floating state. In the cases of tablets containing 20.0% BaSO 4 , only the 40% of total API amount could be dissolved in floating state. In vitro fine resolution X-ray CT imagings were performed to study the volume change and the voxel distributions as a function of HU attenuations by histogram analysis of the images. X-ray detected relative volume change results did not show significant difference between samples. After 24h, all tablets containing BaSO 4 could be segmented, which highlighted the fact that enough BaSO 4 remained in the tablets for their identification. Copyright © 2016 Elsevier B.V. All rights reserved.

Polymeric nanomedicine for cancer MR imaging and drug delivery.

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Khemtong, Chalermchai; Kessinger, Chase W; Gao, Jinming

2009-06-28

Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.

Use of artificial neural networks in drug and explosive detection through tomographic images with thermal neutrons

International Nuclear Information System (INIS)

Ferreira, Francisco J.O.; Crispim, Verginia R.; Silva, Ademir X.

2009-01-01

The artificial neural network technique was used to identify drugs and plastic explosives, from a tomography composed by a set of six neutrongraphic projections obtained in real time. Bidimensional tomographic images of samples of drugs, explosives and other materials, when digitally processed, yield the characteristic spectra of each type of material. The information contained in those spectra was then used for ANN training, the best images being obtained when the multilayer perceptron model, the back-propagation training algorithm and the Cross-validation interruption criterion were used. ANN showed to be useful in forecasting presence of drugs and explosives hitting a rate of success above 97 %. (author)

Drug-loaded poly (ε-caprolactone)/Fe3O4 composite microspheres for magnetic resonance imaging and controlled drug delivery

Science.gov (United States)

Wang, Guangshuo; Zhao, Dexing; Li, Nannan; Wang, Xuehan; Ma, Yingying

2018-06-01

In this study, poly (ε-caprolactone) (PCL) microspheres loading magnetic Fe3O4 nanoparticles and anti-cancer drug of doxorubicin hydrochloride (DOX) were successfully prepared by a modified solvent-evaporation method. The obtained magnetic composite microspheres exhibited dual features of magnetic resonance imaging and controlled drug delivery. The morphology, structure, thermal behavior and magnetic properties of the drug-loaded magnetic microspheres were investigated in detail by SEM, XRD, DSC and SQUID. The obtained composite microspheres showed superparamagnetic behavior and T2-weighted enhancement effect. The drug loading, encapsulation efficiency, releasing behavior and in vitro cytotoxicity of the drug-loaded composite microspheres were systematically investigated. It was found that the values of drug loading and encapsulation efficiency were 36.7% and 25.8%, respectively. The composite microspheres were sensitive to pH and released in a sustained way, and both the release curves under various pH conditions (4.0 and 7.4) were well satisfied with the biphase kinetics function. In addition, the magnetic response of the drug-loaded microspheres was studied and the results showed that the composite microspheres had a good magnetic stability and strong targeting ability.

Specialty pharmacies and other restricted drug distribution systems: financial and safety considerations for patients and health-system pharmacists.

Science.gov (United States)

Kirschenbaum, Bonnie E

2009-12-15

To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a

Elemental distribution imaging by energy-filtering transmission electron microscopy (EFTEM) and its applications

International Nuclear Information System (INIS)

Kurata, Hiroki

1996-01-01

EFTEM is new microscopy with the object of visualizing high resolution quantitative elemental distribution. The measurement principles and the present state of EFTEM studies are explained by the examples of measurement of the elemental distributions. EFTEM is a combination of the transmission electron microscope with the electron energy loss spectroscopy (EFLS). EFTEM method sets the slit in the specific energy field and put the electron passing the slit back in the microscopic image. The qualitative elemental analysis is obtained by observing the position of the absorption end of core electronic excitation spectrum and the quantitative one by determining the core electronic excitation strength of the specific atom depend on filtering with energy selector slit. The binding state and the local structure in the neighborhood of excited atom is determined by the fine structure of absorption end. By the chemical mapping method, the distribution image of chemical binding state is visualized by the imaging chemical map obtained by filtering the specific peak strength of fine structure with the narrow energy selector slit. The fine powder of lead chromate (PbCrO 4 ) covered with silica glass was shown as a typical example of the elemental distribution image of core electronic excitation spectrum. The quantitative analysis method of elemental distribution image is explained. The possibility of single atom analysis at nanometer was shown by the example of nanotube observed by EFTEM. (S.Y.)

Design of shared unit-dose drug distribution network using multi-level particle swarm optimization.

Science.gov (United States)

Chen, Linjie; Monteiro, Thibaud; Wang, Tao; Marcon, Eric

2018-03-01

Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.

Preclinical quantitative MicroPET imaging in evaluation of neuroprotective drug candidates

International Nuclear Information System (INIS)

Son, Ji Yeon; Kim, Yu Kyeong; Kim, Ji Sun; Lee, Byung Chul; Kim, Kyeong Min; Choi, Tae Hyun; Cheon, Gi Jeong; Lee, Won Woo; Kim, Sang Eun

2007-01-01

Using in vivo molecular imaging with microPET/SPECT has been expected to facilitate drug discovery and development. In this study, we applied quantitative microPET to the preclinical evaluation of the effects of two neuroprotective drug candidates to the nigrostriatal dopaminergic neuronal damage. Fifteen SD rats were divided into three groups. The rats of each group were orally administrated one of neuroprotective candidate; NeuProtec (100mg/kg bid) and SureCero (10mg/kg, qd) or normal saline (0.1ml, qd) for 3 weeks. 6-OHDA was sterotactically placed to the right striatum on eighth day after starting while continuing the medication for additional 14 days. [ 124 I]FP-ClT PET scans were obtained using microPET R4 scanner. The behavioral test by amphetamine-induced rotation and the histological examination after thyrosine hydroxylase (TH) immunohistochemical staining were performed. Different uptake in the lesioned striatum among the groups were demonstrated on [ 124 I]FP-CIT PET images. The rats with NeuProtec showed higher binding in the lesion than controls. No differences were observed in SureCere groups. The FP-CIT uptake in the lesioned striatum was well correlated with the % reduction of TH(+) cells (rho =0.73, p=0.025), and also correlated with rotation test (rho =0.79, p=0.001) [ 124 I]FP-CIT animal PET depicted the neuroprotective effects of NeuProtec to the 6-OHDA neurotoxicity in the rat striatum. No demonstrable effect of SureCero might indicate that inadequate dosage was used in this study. MicroPET imaging with small animal could be a great tool in preclinical evaluation of drug efficacy

THE JUST DRUG DISTRIBUTION IN THE PERSPECTIVE OF WELFARE STATE

Directory of Open Access Journals (Sweden)

Aktieva Tri Tjitrawati

2014-03-01

Full Text Available States have obligations to improve equitability of welfare and prosperity of the community. Pharmaceutical is one of the important and strategic industries because of its vital role to support the development of health sector. Lack of regulation on pricing-products, and diversion of social aspects in the drugs trade, either by government or industry, are associated with the paradigm that underlies regulation of the distributions. Prospective policy analysis and functional approach of law are used to find a level of balance of various interest related to the subject, and to find concepts as a basis to construct new paradigm on drugs distribution. Negara berkewajiban untuk meningkatkan kesejahteraan dan kemakmuran masyarakat secara berkeadilan. Industri farmasi merupakan salah satu industri penting dan strategis karena perannya yang vital menunjang pembangunan bidang kesehatan.Terdapat kecenderungan kurangnya peran Pemerintah dalam pricing policy obat, serta diabaikannya aspek sosial dalam perdagangan produk farmasi, baik oleh Pemerintah maupun industri farmasi. Carut marut ini berkaitan dengan ketidakjelasan paradigma yang berujung pada ketidakjelasan kebijakan yang melandasi tatanan distribusi obat. Makalah ini menggunakan analisis kebijakan prospektif dan pendekatan fungsional hukum untuk mengkaji kebijakan distribusi obat yang bersifat multi disiplin dan menemukan konsep baru untuk menemukan titik keseimbangan dari berbagai kepentingan terkait.

G0-WISHART Distribution Based Classification from Polarimetric SAR Images

Science.gov (United States)

Hu, G. C.; Zhao, Q. H.

2017-09-01

Enormous scientific and technical developments have been carried out to further improve the remote sensing for decades, particularly Polarimetric Synthetic Aperture Radar(PolSAR) technique, so classification method based on PolSAR images has getted much more attention from scholars and related department around the world. The multilook polarmetric G0-Wishart model is a more flexible model which describe homogeneous, heterogeneous and extremely heterogeneous regions in the image. Moreover, the polarmetric G0-Wishart distribution dose not include the modified Bessel function of the second kind. It is a kind of simple statistical distribution model with less parameter. To prove its feasibility, a process of classification has been tested with the full-polarized Synthetic Aperture Radar (SAR) image by the method. First, apply multilook polarimetric SAR data process and speckle filter to reduce speckle influence for classification result. Initially classify the image into sixteen classes by H/A/α decomposition. Using the ICM algorithm to classify feature based on the G0-Wshart distance. Qualitative and quantitative results show that the proposed method can classify polaimetric SAR data effectively and efficiently.

A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate Segmentation of Large Fluorescence Microscopy Images.

Science.gov (United States)

Afshar, Yaser; Sbalzarini, Ivo F

2016-01-01

Modern fluorescence microscopy modalities, such as light-sheet microscopy, are capable of acquiring large three-dimensional images at high data rate. This creates a bottleneck in computational processing and analysis of the acquired images, as the rate of acquisition outpaces the speed of processing. Moreover, images can be so large that they do not fit the main memory of a single computer. We address both issues by developing a distributed parallel algorithm for segmentation of large fluorescence microscopy images. The method is based on the versatile Discrete Region Competition algorithm, which has previously proven useful in microscopy image segmentation. The present distributed implementation decomposes the input image into smaller sub-images that are distributed across multiple computers. Using network communication, the computers orchestrate the collectively solving of the global segmentation problem. This not only enables segmentation of large images (we test images of up to 10(10) pixels), but also accelerates segmentation to match the time scale of image acquisition. Such acquisition-rate image segmentation is a prerequisite for the smart microscopes of the future and enables online data compression and interactive experiments.

Distributed decision making in action: diagnostic imaging investigations within the bigger picture.

Science.gov (United States)

Makanjee, Chandra R; Bergh, Anne-Marie; Hoffmann, Willem A

2018-03-01

Decision making in the health care system - specifically with regard to diagnostic imaging investigations - occurs at multiple levels. Professional role players from various backgrounds are involved in making these decisions, from the point of referral to the outcomes of the imaging investigation. The aim of this study was to map the decision-making processes and pathways involved when patients are referred for diagnostic imaging investigations and to explore distributed decision-making events at the points of contact with patients within a health care system. A two-phased qualitative study was conducted in an academic public health complex with the district hospital as entry point. The first phase included case studies of 24 conveniently selected patients, and the second phase involved 12 focus group interviews with health care providers. Data analysis was based on Rapley's interpretation of decision making as being distributed across time, situations and actions, and including different role players and technologies. Clinical decisions incorporating imaging investigations are distributed across the three vital points of contact or decision-making events, namely the initial patient consultation, the diagnostic imaging investigation and the post-investigation consultation. Each of these decision-making events is made up of a sequence of discrete decision-making moments based on the transfer of retrospective, current and prospective information and its transformation into knowledge. This paper contributes to the understanding of the microstructural processes (the 'when' and 'where') involved in the distribution of decisions related to imaging investigations. It also highlights the interdependency in decision-making events of medical and non-medical providers within a single medical encounter. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation

Determination of binder distributions in green-state ceramics by NMR imaging

International Nuclear Information System (INIS)

Garrido, L.; Ackerman, J.L.; Ellingson, W.A.; Weyand, J.D.

1988-03-01

The manufacture of reliable high performance structural ceramics requires a good understanding of the different steps involved in the process. The presence of nonuniformities in the distribution of the polymeric binder could give rise to local fluctuations of density that could produce failure of the ceramic piece. Specimens prepared from Al 2 O 3 with 15 and 2.5% ww binder were imaged using NMR in order to measure binder distribution maps. Results show that NMR imaging could be a useful technique to nondestructively evaluate the quality of green-state specimens. 5 refs., 5 figs

Use of radiopharmaceuticals in the development of drug delivery systems

International Nuclear Information System (INIS)

Frier, M.

1997-01-01

Full text. Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulized solution into the lung, or the residence time of a drug on the cornea. By using the gamma camera to image the in vivo distribution of pharmaceutical formulations radio labelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Example will be shown of studies which examine the rate of transit of orally-administered formulations through the GI tract, as well as describing the development of devices for specific targeting of drugs to the colon. Data will also demonstrate the effectiveness of devices such as spacers in pulmonary drug delivery, in both normal volunteers, and in asthmatic subjects. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers

Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

Science.gov (United States)

Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

2014-04-01

Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All

Distribution of primaquine in human blood: Drug-binding to alpha 1-glycoprotein

International Nuclear Information System (INIS)

Kennedy, E.; Frischer, H.

1990-01-01

To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist

Multiscale Modeling of Antibody Drug Conjugates: Connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy

Science.gov (United States)

Cilliers, Cornelius; Guo, Hans; Liao, Jianshan; Christodolu, Nikolas; Thurber, Greg M.

2016-01-01

Antibody drug conjugates exhibit complex pharmacokinetics due to their combination of macromolecular and small molecule properties. These issues range from systemic concerns, such as deconjugation of the small molecule drug during the long antibody circulation time or rapid clearance from non-specific interactions, to local tumor tissue heterogeneity, cell bystander effects, and endosomal escape. Mathematical models can be used to study the impact of these processes on overall distribution in an efficient manner, and several types of models have been used to analyze varying aspects of antibody distribution including physiologically based pharmacokinetic (PBPK) models and tissue-level simulations. However, these processes are quantitative in nature and cannot be handled qualitatively in isolation. For example, free antibody from deconjugation of the small molecule will impact the distribution of conjugated antibodies within the tumor. To incorporate these effects into a unified framework, we have coupled the systemic and organ-level distribution of a PBPK model with the tissue-level detail of a distributed parameter tumor model. We used this mathematical model to analyze new experimental results on the distribution of the clinical antibody drug conjugate Kadcyla in HER2 positive mouse xenografts. This model is able to capture the impact of the drug antibody ratio (DAR) on tumor penetration, the net result of drug deconjugation, and the effect of using unconjugated antibody to drive ADC penetration deeper into the tumor tissue. This modeling approach will provide quantitative and mechanistic support to experimental studies trying to parse the impact of multiple mechanisms of action for these complex drugs. PMID:27287046

New method for extracting tumors in PET/CT images based on the probability distribution

International Nuclear Information System (INIS)

Nitta, Shuhei; Hontani, Hidekata; Hukami, Tadanori

2006-01-01

In this report, we propose a method for extracting tumors from PET/CT images by referring to the probability distribution of pixel values in the PET image. In the proposed method, first, the organs that normally take up fluorodeoxyglucose (FDG) (e.g., the liver, kidneys, and brain) are extracted. Then, the tumors are extracted from the images. The distribution of pixel values in PET images differs in each region of the body. Therefore, the threshold for detecting tumors is adaptively determined by referring to the distribution. We applied the proposed method to 37 cases and evaluated its performance. This report also presents the results of experiments comparing the proposed method and another method in which the pixel values are normalized for extracting tumors. (author)

Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.

Science.gov (United States)

Banerjee, Abhirup; Maji, Pradipta

2015-12-01

The segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels.

Residues of veterinary drugs in eggs and their distribution between yolk and white

NARCIS (Netherlands)

Kan, C.A.; Petz, M.

2000-01-01

Veterinary drugs and feed additives (especially some coccidiostats) can be absorbed by the digestive tract of laying hens and transferred to the egg. Physicochemical characteristics of these compounds determine their pharmacokinetic behavior and distribution to and within the egg. Traditionally the

EPR imaging of dose distributions aiming at applications in radiation therapy

International Nuclear Information System (INIS)

Lund, E.; Kolbun, N.; Adolfsson, E.; Gustafsson, H.

2014-01-01

A one-dimensional electron paramagnetic resonance (EPR) imaging method for visualisation of dose distributions in photon fields has been developed. Pressed pellets of potassium dithionate were homogeneously irradiated in a 60 Co radiation field to 600 Gy. The EPR analysis was performed with an X-Band (9.6 GHz) Bruker E540 EPR and EPR imaging spectrometer equipped with an E540 GC2X two-axis X-band gradient coil set with gradients along the y axis (along the sample tube) and z axis (along B 0 ) and an ER 4108TMHS resonator. Image reconstruction, including deconvolution, baseline corrections and corrections for the resonator sensitivity, was performed using an in-house-developed Matlab code for the purpose to have a transparent and complete algorithm for image reconstruction. With this method, it is possible to visualise a dose distribution with an accuracy of ∼5 % within ±5 mm from the centre of the resonator. (authors)

Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants.

Science.gov (United States)

Markovic, Stacey; Belz, Jodi; Kumar, Rajiv; Cormack, Robert A; Sridhar, Srinivas; Niedre, Mark

2016-01-01

Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform.

Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

International Nuclear Information System (INIS)

Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa; Sanz-Viedma, Salome; Garcia-Solis, David; Mir, Pablo

2010-01-01

To determine clinical predictors and accuracy of 123 I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and 123 I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p 123 I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by 123 I-FP-CIT SPECT imaging. (orig.)

A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate Segmentation of Large Fluorescence Microscopy Images

Science.gov (United States)

Afshar, Yaser; Sbalzarini, Ivo F.

2016-01-01

Modern fluorescence microscopy modalities, such as light-sheet microscopy, are capable of acquiring large three-dimensional images at high data rate. This creates a bottleneck in computational processing and analysis of the acquired images, as the rate of acquisition outpaces the speed of processing. Moreover, images can be so large that they do not fit the main memory of a single computer. We address both issues by developing a distributed parallel algorithm for segmentation of large fluorescence microscopy images. The method is based on the versatile Discrete Region Competition algorithm, which has previously proven useful in microscopy image segmentation. The present distributed implementation decomposes the input image into smaller sub-images that are distributed across multiple computers. Using network communication, the computers orchestrate the collectively solving of the global segmentation problem. This not only enables segmentation of large images (we test images of up to 1010 pixels), but also accelerates segmentation to match the time scale of image acquisition. Such acquisition-rate image segmentation is a prerequisite for the smart microscopes of the future and enables online data compression and interactive experiments. PMID:27046144

A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate Segmentation of Large Fluorescence Microscopy Images.

Directory of Open Access Journals (Sweden)

Yaser Afshar

Full Text Available Modern fluorescence microscopy modalities, such as light-sheet microscopy, are capable of acquiring large three-dimensional images at high data rate. This creates a bottleneck in computational processing and analysis of the acquired images, as the rate of acquisition outpaces the speed of processing. Moreover, images can be so large that they do not fit the main memory of a single computer. We address both issues by developing a distributed parallel algorithm for segmentation of large fluorescence microscopy images. The method is based on the versatile Discrete Region Competition algorithm, which has previously proven useful in microscopy image segmentation. The present distributed implementation decomposes the input image into smaller sub-images that are distributed across multiple computers. Using network communication, the computers orchestrate the collectively solving of the global segmentation problem. This not only enables segmentation of large images (we test images of up to 10(10 pixels, but also accelerates segmentation to match the time scale of image acquisition. Such acquisition-rate image segmentation is a prerequisite for the smart microscopes of the future and enables online data compression and interactive experiments.

MO-FG-204-08: Optimization-Based Image Reconstruction From Unevenly Distributed Sparse Projection Views

International Nuclear Information System (INIS)

Xie, Huiqiao; Yang, Yi; Tang, Xiangyang; Niu, Tianye; Ren, Yi

2015-01-01

Purpose: Optimization-based reconstruction has been proposed and investigated for reconstructing CT images from sparse views, as such the radiation dose can be substantially reduced while maintaining acceptable image quality. The investigation has so far focused on reconstruction from evenly distributed sparse views. Recognizing the clinical situations wherein only unevenly sparse views are available, e.g., image guided radiation therapy, CT perfusion and multi-cycle cardiovascular imaging, we investigate the performance of optimization-based image reconstruction from unevenly sparse projection views in this work. Methods: The investigation is carried out using the FORBILD and an anthropomorphic head phantoms. In the study, 82 views, which are evenly sorted out from a full (360°) axial CT scan consisting of 984 views, form sub-scan I. Another 82 views are sorted out in a similar manner to form sub-scan II. As such, a CT scan with sparse (164) views at 1:6 ratio are formed. By shifting the two sub-scans relatively in view angulation, a CT scan with unevenly distributed sparse (164) views at 1:6 ratio are formed. An optimization-based method is implemented to reconstruct images from the unevenly distributed views. By taking the FBP reconstruction from the full scan (984 views) as the reference, the root mean square (RMS) between the reference and the optimization-based reconstruction is used to evaluate the performance quantitatively. Results: In visual inspection, the optimization-based method outperforms the FBP substantially in the reconstruction from unevenly distributed, which are quantitatively verified by the RMS gauged globally and in ROIs in both the FORBILD and anthropomorphic head phantoms. The RMS increases with increasing severity in the uneven angular distribution, especially in the case of anthropomorphic head phantom. Conclusion: The optimization-based image reconstruction can save radiation dose up to 12-fold while providing acceptable image quality

pH-sensitive Au–BSA–DOX–FA nanocomposites for combined CT imaging and targeted drug delivery

Directory of Open Access Journals (Sweden)

Huang H

2017-04-01

Full Text Available He Huang,1 Da-Peng Yang,2 Minghuan Liu,2 Xiangsheng Wang,1 Zhiyong Zhang,1 Guangdong Zhou,1 Wei Liu,1 Yilin Cao,1 Wen Jie Zhang,1 Xiansong Wang1 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai, 2College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou, People’s Republic of China Abstract: Albumin-based nanoparticles (NPs as a drug delivery system have attracted much attention owing to their nontoxicity, non-immunogenicity, great stability and ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA was utilized as a template to prepare Au–BSA core/shell NPs. The outer layer BSA was subsequently conjugated with cis-aconityl doxorubicin (DOX and folic acid (FA to create Au–BSA–DOX–FA nanocomposites. A list of characterizations was undertaken to identify the successful conjugation of drug molecules and targeted agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8 assay indicated that Au–BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells in the concentration range of 0–100 µg/mL, which can therefore be used as a safe drug delivery carrier. Furthermore, compared with free DOX, Au–BSA–DOX–FA nanocomposites exhibited a pH-sensitive drug release ability and superior antitumor activity in a drug concentration-dependent manner. In vivo computed tomography (CT imaging experiments showed that Au–BSA–DOX–FA nanocomposites could be used as an efficient and durable CT contrast agent for targeted CT imaging of the folate receptor (FR overexpressed in cancer tissues. In vivo antitumor experiments demonstrated that Au–BSA–DOX–FA nanocomposites have selective antitumor activity effects on FR-overexpressing tumors and no adverse effects on normal tissues and

21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

Science.gov (United States)

2010-04-01

... OTC test sample collection systems for drugs of abuse testing. 809.40 Section 809.40 Food and Drugs... Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs of abuse testing. (a) Over-the-counter (OTC) test sample collection systems for drugs of abuse testing (§ 864.3260...

Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

Science.gov (United States)

Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

2017-11-15

The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

Examining the spatial distribution of law enforcement encounters among people who inject drugs after implementation of Mexico's drug policy reform.

Science.gov (United States)

Gaines, Tommi L; Beletsky, Leo; Arredondo, Jaime; Werb, Daniel; Rangel, Gudelia; Vera, Alicia; Brouwer, Kimberly

2015-04-01

In 2009, Mexico decriminalized the possession of small amounts of illicit drugs for personal use in order to refocus law enforcement resources on drug dealers and traffickers. This study examines the spatial distribution of law enforcement encounters reported by people who inject drugs (PWID) in Tijuana, Mexico to identify concentrated areas of policing activity after implementation of the new drug policy. Mapping the physical location of law enforcement encounters provided by PWID (n = 461) recruited through targeted sampling, we identified hotspots of extra-judicial encounters (e.g., physical/sexual abuse, syringe confiscation, and money extortion by law enforcement) and routine authorized encounters (e.g., being arrested or stopped but not arrested) using point density maps and the Getis-Ord Gi* statistic calculated at the neighborhood-level. Approximately half of the participants encountered law enforcement more than once in a calendar year and nearly one third of these encounters did not result in arrest but involved harassment or abuse by law enforcement. Statistically significant hotspots of law enforcement encounters were identified in a limited number of neighborhoods located in areas with known drug markets. At the local-level, law enforcement activities continue to target drug users despite a national drug policy that emphasizes drug treatment diversion rather than punitive enforcement. There is a need for law enforcement training and improved monitoring of policing tactics to better align policing with public health goals.

Change detection in polarimetric SAR images using complex Wishart distributed matrices

DEFF Research Database (Denmark)

Conradsen, Knut; Nielsen, Allan Aasbjerg; Skriver, Henning

In surveillance it is important to be able to detect natural or man-made changes e.g. based on sequences of satellite or air borne images of the same area taken at different times. The mapping capability of synthetic aperture radar (SAR) is independent of e.g. cloud cover, and thus this technology...... scattering matrix, and after suitable preprocessing the outcome at each picture element (pixel) may be represented as a 3 by 3 Hermitian matrix following a complex Wishart distribution. One approach to solving the change detection problem based on SAR images is therefore to apply suitable statistical tests...... in the complex Wishart distribution. We propose a set-up for a systematic solution to the (practical) problems using the likelihood ratio test statistics. We show some examples based on a time series of images with 1024 by 1024 pixels....

Evaluating visibility of age spot and freckle based on simulated spectral reflectance distribution and facial color image

Science.gov (United States)

Hirose, Misa; Toyota, Saori; Tsumura, Norimichi

2018-02-01

In this research, we evaluate the visibility of age spot and freckle with changing the blood volume based on simulated spectral reflectance distribution and the actual facial color images, and compare these results. First, we generate three types of spatial distribution of age spot and freckle in patch-like images based on the simulated spectral reflectance. The spectral reflectance is simulated using Monte Carlo simulation of light transport in multi-layered tissue. Next, we reconstruct the facial color image with changing the blood volume. We acquire the concentration distribution of melanin, hemoglobin and shading components by applying the independent component analysis on a facial color image. We reproduce images using the obtained melanin and shading concentration and the changed hemoglobin concentration. Finally, we evaluate the visibility of pigmentations using simulated spectral reflectance distribution and facial color images. In the result of simulated spectral reflectance distribution, we found that the visibility became lower as the blood volume increases. However, we can see that a specific blood volume reduces the visibility of the actual pigmentations from the result of the facial color images.

Mass-storage management for distributed image/video archives

Science.gov (United States)

Franchi, Santina; Guarda, Roberto; Prampolini, Franco

1993-04-01

The realization of image/video database requires a specific design for both database structures and mass storage management. This issue has addressed the project of the digital image/video database system that has been designed at IBM SEMEA Scientific & Technical Solution Center. Proper database structures have been defined to catalog image/video coding technique with the related parameters, and the description of image/video contents. User workstations and servers are distributed along a local area network. Image/video files are not managed directly by the DBMS server. Because of their wide size, they are stored outside the database on network devices. The database contains the pointers to the image/video files and the description of the storage devices. The system can use different kinds of storage media, organized in a hierarchical structure. Three levels of functions are available to manage the storage resources. The functions of the lower level provide media management. They allow it to catalog devices and to modify device status and device network location. The medium level manages image/video files on a physical basis. It manages file migration between high capacity media and low access time media. The functions of the upper level work on image/video file on a logical basis, as they archive, move and copy image/video data selected by user defined queries. These functions are used to support the implementation of a storage management strategy. The database information about characteristics of both storage devices and coding techniques are used by the third level functions to fit delivery/visualization requirements and to reduce archiving costs.

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

Science.gov (United States)

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

Image illumination enhancement with an objective no-reference measure of illumination assessment based on Gaussian distribution mapping

Directory of Open Access Journals (Sweden)

Gholamreza Anbarjafari

2015-12-01

Full Text Available Illumination problems have been an important concern in many image processing applications. The pattern of the histogram on an image introduces meaningful features; hence within the process of illumination enhancement, it is important not to destroy such information. In this paper we propose a method to enhance image illumination using Gaussian distribution mapping which also keeps the information laid on the pattern of the histogram on the original image. First a Gaussian distribution based on the mean and standard deviation of the input image will be calculated. Simultaneously a Gaussian distribution with the desired mean and standard deviation will be calculated. Then a cumulative distribution function of each of the Gaussian distributions will be calculated and used in order to map the old pixel value onto the new pixel value. Another important issue in the field of illumination enhancement is absence of a quantitative measure for the assessment of the illumination of an image. In this research work, a quantitative measure indicating the illumination state, i.e. contrast level and brightness of an image, is also proposed. The measure utilizes the estimated Gaussian distribution of the input image and the Kullback-Leibler Divergence (KLD between the estimated Gaussian and the desired Gaussian distributions to calculate the quantitative measure. The experimental results show the effectiveness and the reliability of the proposed illumination enhancement technique, as well as the proposed illumination assessment measure over conventional and state-of-the-art techniques.

Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

International Nuclear Information System (INIS)

Durgadas, C. V.; Sharma, C. P.; Paul, W.; Rekha, M. R.; Sreenivasan, K.

2012-01-01

This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5–5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.Graphical AbstractDrug release induced particle aggregation enhances Raman signals to aid in imaging.

Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

2013-01-15

Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

Image quality of microcalcifications in digital breast tomosynthesis: Effects of projection-view distributions

International Nuclear Information System (INIS)

Lu, Yao; Chan, Heang-Ping; Wei, Jun; Goodsitt, Mitch; Carson, Paul L.; Hadjiiski, Lubomir; Schmitz, Andrea; Eberhard, Jeffrey W.; Claus, Bernhard E. H.

2011-01-01

Purpose: To analyze the effects of projection-view (PV) distribution on the contrast and spatial blurring of microcalcifications on the tomosynthesized slices (X-Y plane) and along the depth (Z) direction for the same radiation dose in digital breast tomosynthesis (DBT). Methods: A GE GEN2 prototype DBT system was used for acquisition of DBT scans. The system acquires PV images from 21 angles in 3 deg. increments over a ±30 deg. range. From these acquired PV images, the authors selected six subsets of PV images to simulate DBT of different angular ranges and angular increments. The number of PV images in each subset was fixed at 11 to simulate a constant total dose. These different PV distributions were subjectively divided into three categories: uniform group, nonuniform central group, and nonuniform extreme group with different angular ranges and angular increments. The simultaneous algebraic reconstruction technique (SART) was applied to each subset to reconstruct the DBT slices. A selective diffusion regularization method was employed to suppress noise. The image quality of microcalcifications in the reconstructed DBTs with different PV distributions was compared using the DBT scans of an American College of Radiology phantom and three human subjects. The contrast-to-noise ratio (CNR) and the full width at half maximum (FWHM) of the line profiles of microcalcifications within their in-focus DBT slices (parallel to detector plane) and the FWHMs of the interplane artifact spread function (ASF) in the Z-direction (perpendicular to detector plane) were used as image quality measures. Results: The results indicate that DBT acquired with a large angular range or, for an equal angular range,with a large fraction of PVs at large angles yielded superior ASF with smaller FWHM in the Z-direction. PV distributions with a narrow angular range or a large fraction of PVs at small angles had stronger interplane artifacts. In the X-Y focal planes, the effect of PV

Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Science.gov (United States)

Lamprou, Dimitrios A.; Venkatpurwar, Vinod; Kumar, M. N. V. Ravi

2013-01-01

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ∼280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics. PMID:23724054

How well do time-integrated Kα images represent hot electron spatial distributions?

Science.gov (United States)

Ovchinnikov, V. M.; Kemp, G. E.; Schumacher, D. W.; Freeman, R. R.; Van Woerkom, L. D.

2011-07-01

A computational study is described, which addresses how well spatially resolved time-integrated Kα images recorded in intense laser-plasma experiments correlate with the distribution of "hot" (>1 MeV) electrons as they propagate through the target. The hot electron angular distribution leaving the laser-plasma region is critically important for many applications such as Fast Ignition or laser based x-ray sources; and Kα images are commonly used as a diagnostic. It is found that Kα images can easily mislead due to refluxing and other effects. Using the particle-in-cell code LSP, it is shown that a Kα image is not solely determined by the initial population of forward directed hot electrons, but rather also depends upon "delayed" hot electrons, and in fact continues to evolve long after the end of the laser interaction. Of particular note, there is a population of hot electrons created during the laser-plasma interaction that acquire a velocity direction opposite that of the laser and subsequently reflux off the front surface of the target, deflect when they encounter magnetic fields in the laser-plasma region, and then traverse the target in a wide spatial distribution. These delayed fast electrons create significant features in the Kα time-integrated images. Electrons refluxing from the sides and the back of the target are also found to play a significant role in forming the final Kα image. The relative contribution of these processes is found to vary depending on depth within target. These effects make efforts to find simple correlations between Kα images and, for example, Fast Ignition relevant parameters prone to error. Suggestions for future target design are provided.

Effect of background radiation shielding on natural radioactivity distribution measurement with imaging plate

International Nuclear Information System (INIS)

Mori, C.; Suzuki, T.; Koido, S.; Uritani, A.; Miyahara, H.; Yanagida, K.; Miyahara, J.; Takahashi, K.

1996-01-01

Distribution images of natural radioactivity contained in various natural materials such as vegetable, animal meat and pottery work can be obtained with an imaging plate which has high sensitivity for nuclear radiations. For such very low levels of radioactivity, natural background radiations must be reduced using a shielding box. The lining, on the inside of the box, with low atomic number material such as acrylic resin is very effective in reducing electrons, β-rays and low energy X- and γ-rays emitted from the inner surface of the shielding material. Some images of natural radioactivity distribution were obtained and the radioactivity, mainly 40 K, contained in natural materials was measured by using an HPGe detector and also the imaging plate itself. (orig.)

Chemical mapping of pharmaceutical cocrystals using terahertz spectroscopic imaging.

Science.gov (United States)

Charron, Danielle M; Ajito, Katsuhiro; Kim, Jae-Young; Ueno, Yuko

2013-02-19

Terahertz (THz) spectroscopic imaging is a promising technique for distinguishing pharmaceuticals of similar molecular composition but differing crystal structures. Physicochemical properties, for instance bioavailability, are manipulated by altering a drug's crystal structure through methods such as cocrystallization. Cocrystals are molecular complexes having crystal structures different from those of their pure components. A technique for identifying the two-dimensional distribution of these alternate forms is required. Here we present the first demonstration of THz spectroscopic imaging of cocrystals. THz spectra of caffeine-oxalic acid cocrystal measured at low temperature exhibit sharp peaks, enabling us to visualize the cocrystal distribution in nonuniform tablets. The cocrystal distribution was clearly identified using THz spectroscopic data, and the cocrystal concentration was calculated with 0.3-1.3% w/w error from the known total concentration. From this result, THz spectroscopy allows quantitative chemical mapping of cocrystals and offers researchers and drug developers a new analytical tool.

Gold nanorods contained polyvinyl alcohol/chitosan nanofiber matrix for cell imaging and drug delivery

Energy Technology Data Exchange (ETDEWEB)

Yan, Eryun, E-mail: yaney359@126.com [College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Cao, Minglu [College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006 (China); Wang, Yuwei; Hao, Xiaoyuan [College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Pei, Shichun; Gao, Jianwei; Wang, Yan [College of Food and Biological Engineering, Qiqihar University, Qiqihar 161006 (China); Zhang, Zhuanfang [College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006 (China); Zhang, Deqing, E-mail: zhdqing@163.com [College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China)

2016-01-01

Gold nanorods (AuNRs) that contained polyvinyl alcohol/chitosan (PVA/CS) hybrid nanofibers with dual functions are successfully fabricated by a simple electrospinning method. The results of transmission electron microscopy (TEM), X-ray diffraction (XRD) and energy dispersive X-ray (EDX) spectroscopy indicate that AuNRs are indeed encapsulated into the PVA/CS hybrid nanofibers. FTIR spectra results demonstrate that the chemical structures of PVA and CS are not affected when the AuNRs are introduced into the fibers. In vitro cytotoxicity test reveals that the hybrid fibers involving AuNRs are completely biocompatible. The as-prepared fibers can be used as a carrier for anticancer agent doxorubicin (DOX), and the drug is delivered into the cell nucleus. The AuNRs and DOX incorporated fibers are effective for inhibiting the growth and proliferation of ovary cancer cells and they can also be used as the cell imaging agent due to the unique optical properties of AuNRs. The nanofiber matrix combining two functions of cell imaging and drug delivery may be of great application potential in biomedical-related areas. - Highlights: • The AuNRs contained PVA/CS nanofibers are fabricated by electrospinning. • The hybrid fibers involving AuNRs are completely biocompatible. • The DOX loaded fibers are effective for inhibiting the proliferation of cancer cells. • The nanofibers combined two functions of cell imaging and drug delivery.

Quantum dots in imaging, drug delivery and sensor applications.

Science.gov (United States)

Matea, Cristian T; Mocan, Teodora; Tabaran, Flaviu; Pop, Teodora; Mosteanu, Ofelia; Puia, Cosmin; Iancu, Cornel; Mocan, Lucian

2017-01-01

Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.

Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology

Science.gov (United States)

Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

2014-01-01

Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience. PMID:23966069

Mass spectrometry imaging, an emerging technology in neuropsychopharmacology.

Science.gov (United States)

Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

2014-01-01

Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience.

Imaging and Measuring Electron Beam Dose Distributions Using Holographic Interferometry

DEFF Research Database (Denmark)

Miller, Arne; McLaughlin, W. L.

1975-01-01

Holographic interferometry was used to image and measure ionizing radiation depth-dose and isodose distributions in transparent liquids. Both broad and narrowly collimated electron beams from accelerators (2–10 MeV) provided short irradiation times of 30 ns to 0.6 s. Holographic images...... and measurements of absorbed dose distributions were achieved in liquids of various densities and thermal properties and in water layers thinner than the electron range and with backings of materials of various densities and atomic numbers. The lowest detectable dose in some liquids was of the order of a few k......Rad. The precision limits of the measurement of dose were found to be ±4%. The procedure was simple and the holographic equipment stable and compact, thus allowing experimentation under routine laboratory conditions and limited space....

Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET

International Nuclear Information System (INIS)

Mishina, Masahiro; Senda, Michio; Kimura, Yuichi

2000-01-01

Accumulation of [ 11 C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of ''static scan'' images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [ 11 C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the static scan'' images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [ 11 C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection. (author)

A prototype distributed object-oriented architecture for image-based automatic laser alignment

International Nuclear Information System (INIS)

Stout, E.A.; Kamm, V.J.M.; Spann, J.M.; Van Arsdall, P.J.

1996-01-01

Designing a computer control system for the National Ignition Facility (NIF) is a complex undertaking because of the system's large size and its distributed nature. The controls team is addressing that complexity by adopting the object-oriented programming paradigm, designing reusable software frameworks, and using the Common Object Request Broker Architecture (CORBA) for distribution. A prototype system for image-based automatic laser alignment has been developed to evaluate and gain experience with CORBA and OOP in a small distributed system. The prototype is also important in evaluating alignment concepts, image processing techniques, speed and accuracy of automatic alignment objectives for the NIF, and control hardware for aligment devices. The prototype system has met its inital objectives and provides a basis for continued development

Molecular imaging in drug development: Update and challenges for radiolabeled antibodies and nanotechnology.

Science.gov (United States)

Colombo, Ilaria; Overchuk, Marta; Chen, Juan; Reilly, Raymond M; Zheng, Gang; Lheureux, Stephanie

2017-11-01

Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent. The small therapeutic index of most anticancer agents is a limitation in the drug development process. Incorporation of molecular imaging in clinical research may help in overcoming this limitation and favouring selection of patient populations most likely to achieve benefit from targeted therapy. This review will focus on two of the most advanced theranostic approaches with promising potential for application in the clinic: 1) therapeutic monoclonal antibodies which may be linked to a radionuclide for SPECT or PET imaging to guide cancer diagnosis, staging, molecular characterization, and assessment of the response to treatment and 2) multifunctional nanotechnology that allows image guided drug delivery through encapsulation of multiple therapeutic, targeting and imaging agents into a single nanoparticle. Porphysome, a liposome-like nanoparticle, is an example of a novel and promising application of nanotechnology for cancer diagnosis and treatment. These technologies have proven to be effective in preclinical models, warranting further clinical investigation to advance their application for the benefit of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.

Science.gov (United States)

Krishnaiah, Yellela S R; Katragadda, Usha; Khan, Mansoor A

2014-05-01

Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Cross-correlated imaging of distributed mode filtering rod fiber

DEFF Research Database (Denmark)

Laurila, Marko; Barankov, Roman; Jørgensen, Mette Marie

2013-01-01

We analyze the modal properties of an 85μm core distributed mode filtering rod fiber using cross-correlated (C2) imaging. We evaluate suppression of higher-order modes (HOMs) under severely misaligned mode excitation and identify a single-mode regime where HOMs are suppressed by more than 20dB....

Visualization of pigment distributions in paintings using synchrotron K-edge imaging

International Nuclear Information System (INIS)

Krug, K.; Dik, J.; Leeuw, M.; Whitson, A. den; Tortora, J.; Coan, P.; Nemoz, C.; Bravin, A.

2006-01-01

X-ray radiography plays an important role in the study of artworks and archaeological artifacts. The internal structure of objects provides information on genesis, authenticity, painting technique, material condition and conservation history. Transmission radiography, however, does not provide information on the exact elemental composition of objects and heavy metal layers can shadow or obscure the ones including lighter elements. This paper presents the first application of synchrotron-based K-edge absorption imaging applied to paintings. Using highly monochromatic radiation, K-edge imaging is used to obtain elemental distribution images over large areas. Such elemental maps visualize the distribution of an individual pigment throughout the paint stratigraphy. This provides color information on hidden paint layers, which is of great relevance to art historians and painting conservators. The main advantage is the quick data acquisition time and the sensitivity to elements throughout the entire paint stratigraphy. The examination of a test painting is shown and further instrumental developments are discussed. (orig.)

Coded aperture imaging of alpha source spatial distribution

International Nuclear Information System (INIS)

Talebitaher, Alireza; Shutler, Paul M.E.; Springham, Stuart V.; Rawat, Rajdeep S.; Lee, Paul

2012-01-01

The Coded Aperture Imaging (CAI) technique has been applied with CR-39 nuclear track detectors to image alpha particle source spatial distributions. The experimental setup comprised: a 226 Ra source of alpha particles, a laser-machined CAI mask, and CR-39 detectors, arranged inside a vacuum enclosure. Three different alpha particle source shapes were synthesized by using a linear translator to move the 226 Ra source within the vacuum enclosure. The coded mask pattern used is based on a Singer Cyclic Difference Set, with 400 pixels and 57 open square holes (representing ρ = 1/7 = 14.3% open fraction). After etching of the CR-39 detectors, the area, circularity, mean optical density and positions of all candidate tracks were measured by an automated scanning system. Appropriate criteria were used to select alpha particle tracks, and a decoding algorithm applied to the (x, y) data produced the de-coded image of the source. Signal to Noise Ratio (SNR) values obtained for alpha particle CAI images were found to be substantially better than those for corresponding pinhole images, although the CAI-SNR values were below the predictions of theoretical formulae. Monte Carlo simulations of CAI and pinhole imaging were performed in order to validate the theoretical SNR formulae and also our CAI decoding algorithm. There was found to be good agreement between the theoretical formulae and SNR values obtained from simulations. Possible reasons for the lower SNR obtained for the experimental CAI study are discussed.

Effect of vitamin D3, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues

International Nuclear Information System (INIS)

Carr, E.A. Jr.; Carroll, M.; Montes, M.

1981-01-01

Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, we studied effects of various stable compounds (as a single, large dose or fractionated into short series) on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B). Vitamin D3s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. The hypercalcemia was accompanied by increased [Ca] in the lesion. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 hr before killing increased uptake by lesion, increasing L/B from 0.19 +/- 0.03 to 0.45 +/- 0.08 (p less than 0.01), with no change in serum [Ca] and minimal changes in serum [P], [Na], and [K]. DOCA also increased the lesion-to-blood ratio from 6.5 +/- 0.07 to 15.4 +/- 3.9 (p less than 0.05). These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents

Drug targeting and the carriers. Application to chemoembolization and medical imaging

International Nuclear Information System (INIS)

Puisieux, F.; Benoit, J.P.; Roblot-Treupel, L.

1987-01-01

The last fifteen years have seen an increased interest in drug targeting which can be considered as a new way to control the body distribution of drugs when associated with an appropriate carrier. The systems currently studied possess different structures (macromolecular, vesicular and particular) and can be classified into carriers of first, second and third generation. After a brief review of the three types of carriers, this paper focuses on their respective interest in the different fields of radiology: carriers of first generation (microcapsules, microspheres) in chemoembolization, carriers of second generation (liposomes, nanocapsules, nanospheres) in conventional radiology, in computerized tomography, in scintigraphy, in RMN; carriers of third generation (monoclonal antibodies...) in immunoscintigraphy of tumors [fr

Characterization of water distribution in bread during storage using magnetic resonance imaging.

Science.gov (United States)

Lodi, Alessia; Abduljalil, Amir M; Vodovotz, Yael

2007-12-01

A soy bread of fully acceptable quality and containing 49% soy ingredients (with or without 5% almond powder) has been recently developed in our laboratory. An investigation on water distribution and mobility, as probed by proton signal intensity and T2 magnetic resonance images, during storage was designed to examine possible relations between water states and hindered staling rate upon soy or soy-almond addition. Water proton distribution throughout soy-containing loaves was found to be very homogeneous in fresh breads with and without almond, with minimal water migration occurring during prolonged storage. In contrast, traditional wheat bread displayed an inhomogeneous water proton population that tended to change (with higher moisture migration towards the outer perimeter of the slice) during storage. Similar results were found for water mobility throughout the loaves, as depicted in T2 images. On intensity images of all considered bread varieties, the outer perimeter corresponding to the crust exhibited lower signal intensity due to decreased water content. Higher T2 values were found in the crust of soy breads with and without almond, which were attributed to lipids. The results indicated that the addition of soy to bread improved the homogeneous distribution of water molecules, which may hinder the staling rate of soy-containing breads. However, incorporation of almond had little effect on the water proton distribution or mobility of soy breads.

Pathogen infection distribution and drug resistance analysis of patients with severe liver disease

Directory of Open Access Journals (Sweden)

Xi CHEN

2018-04-01

Full Text Available Objective　To explore the infection distribution and drug resistance of pathogens in patients with severe liver disease, and provide reference for clinical medication. Methods　Retrospective analysis of the microbiological specimens from patients with severe liver disease in Department of Infection of our hospital from August 2014 to November 2016 and the drug susceptibility testing were carried out by means of K-B disc diffusion method after bacterial culturing, and the distribution and drug resistance of pathogens were analyzed. Results　Totally 17 of 73 patients with severe liver disease developed hospital infection (23.3%. 104 strains of bacteria were isolated and 78 strains out of them were multidrug-resistant bacteria (75.0%. Among them, 28(26.9% strains were gram-positive coccus, mainly consisting of Staphylococcus aureus and Staphylococcus epidermidis, and 58(55.8% were gram-negative coccus, mainly composed of Escherichia coli, Klebsiella pneumonia and Acinetobacter baumannii, and 18(17.3% strains fungi. S.aureus and enterococci were resistant to penicillin, erythromycin and levofloxacin, the resistance rates were above 80.0%, but had low resistance rates to vancomycin, teicoplanin and tigecycline. The resistance rates of E.coli and K.pneumoniae to piperacillin, cefazolin and cefuroxime sodium were above 85.0%, but they had lower resistance rates to tigecycline and amikacin. Acinetobacter baumannii was 100% resistant to piperacillin and tazobactam, ceftazidime, imipenem and amikacin, but had low resistance to tigecycline and minocycline. Conclusions　Multi-drug resistant bacteria are the main bacterial pathogens in patients with severe liver disease and have a high resistance rate to commonly used antibiotics, empirical treatment in the population at high risk of multidrug-resistant bacteria infections requires the use of broad-spectrum or high-grade antibiotics (e.g. carbapenems or tigecycline and drugs against specific pathogenic

Learning with distribution of optimized features for recognizing common CT imaging signs of lung diseases

Science.gov (United States)

Ma, Ling; Liu, Xiabi; Fei, Baowei

2017-01-01

Common CT imaging signs of lung diseases (CISLs) are defined as the imaging signs that frequently appear in lung CT images from patients. CISLs play important roles in the diagnosis of lung diseases. This paper proposes a novel learning method, namely learning with distribution of optimized feature (DOF), to effectively recognize the characteristics of CISLs. We improve the classification performance by learning the optimized features under different distributions. Specifically, we adopt the minimum spanning tree algorithm to capture the relationship between features and discriminant ability of features for selecting the most important features. To overcome the problem of various distributions in one CISL, we propose a hierarchical learning method. First, we use an unsupervised learning method to cluster samples into groups based on their distribution. Second, in each group, we use a supervised learning method to train a model based on their categories of CISLs. Finally, we obtain multiple classification decisions from multiple trained models and use majority voting to achieve the final decision. The proposed approach has been implemented on a set of 511 samples captured from human lung CT images and achieves a classification accuracy of 91.96%. The proposed DOF method is effective and can provide a useful tool for computer-aided diagnosis of lung diseases on CT images.

Multispectral UV imaging for surface analysis of MUPS tablets with special focus on the pellet distribution

DEFF Research Database (Denmark)

Novikova, Anna; Carstensen, Jens Michael; Rades, Thomas

2016-01-01

In the present study the applicability of multispectral UV imaging in combination with multivariate image analysis for surface evaluation of MUPS tablets was investigated with respect to the differentiation of the API pellets from the excipients matrix, estimation of the drug content as well as p...... image analysis is a promising approach for the automatic quality control of MUPS tablets during the manufacturing process....

Real-Time Two-Dimensional Magnetic Particle Imaging for Electromagnetic Navigation in Targeted Drug Delivery

Science.gov (United States)

Le, Tuan-Anh; Zhang, Xingming; Hoshiar, Ali Kafash; Yoon, Jungwon

2017-01-01

Magnetic nanoparticles (MNPs) are effective drug carriers. By using electromagnetic actuated systems, MNPs can be controlled noninvasively in a vascular network for targeted drug delivery (TDD). Although drugs can reach their target location through capturing schemes of MNPs by permanent magnets, drugs delivered to non-target regions can affect healthy tissues and cause undesirable side effects. Real-time monitoring of MNPs can improve the targeting efficiency of TDD systems. In this paper, a two-dimensional (2D) real-time monitoring scheme has been developed for an MNP guidance system. Resovist particles 45 to 65 nm in diameter (5 nm core) can be monitored in real-time (update rate = 2 Hz) in 2D. The proposed 2D monitoring system allows dynamic tracking of MNPs during TDD and renders magnetic particle imaging-based navigation more feasible. PMID:28880220

Linearized image reconstruction method for ultrasound modulated electrical impedance tomography based on power density distribution

International Nuclear Information System (INIS)

Song, Xizi; Xu, Yanbin; Dong, Feng

2017-01-01

Electrical resistance tomography (ERT) is a promising measurement technique with important industrial and clinical applications. However, with limited effective measurements, it suffers from poor spatial resolution due to the ill-posedness of the inverse problem. Recently, there has been an increasing research interest in hybrid imaging techniques, utilizing couplings of physical modalities, because these techniques obtain much more effective measurement information and promise high resolution. Ultrasound modulated electrical impedance tomography (UMEIT) is one of the newly developed hybrid imaging techniques, which combines electric and acoustic modalities. A linearized image reconstruction method based on power density is proposed for UMEIT. The interior data, power density distribution, is adopted to reconstruct the conductivity distribution with the proposed image reconstruction method. At the same time, relating the power density change to the change in conductivity, the Jacobian matrix is employed to make the nonlinear problem into a linear one. The analytic formulation of this Jacobian matrix is derived and its effectiveness is also verified. In addition, different excitation patterns are tested and analyzed, and opposite excitation provides the best performance with the proposed method. Also, multiple power density distributions are combined to implement image reconstruction. Finally, image reconstruction is implemented with the linear back-projection (LBP) algorithm. Compared with ERT, with the proposed image reconstruction method, UMEIT can produce reconstructed images with higher quality and better quantitative evaluation results. (paper)

A Novel Multiparametric Drug-Scoring Method for High-Throughput Screening of 3D Multicellular Tumor Spheroids Using the Celigo Image Cytometer.

Science.gov (United States)

Cribbes, Scott; Kessel, Sarah; McMenemy, Scott; Qiu, Jean; Chan, Leo Li-Ying

2017-06-01

Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates. Using parameters such as MCTS diameter and invasion area, growth and invasion were monitored for 9 and 3 d, respectively. Furthermore, fluorescent staining with calcein AM, propidium iodide, Hoechst 33342, and caspase 3/7 was performed at day 9 posttreatment to measure viability and apoptosis. Using the kinetic and endpoint data generated, we created a novel multiparametric drug-scoring system for 3D MCTS that can be used to identify and classify potential drug candidates earlier in the drug discovery process. Furthermore, the combination of quantitative and qualitative image data can be used to delineate differences between drugs that induce cytotoxic and cytostatic effects. The 3D MCTS-based multiparametric scoring method described here can provide an alternative screening method to better qualify tested drug compounds.

Mapping stain distribution in pathology slides using whole slide imaging

Directory of Open Access Journals (Sweden)

Fang-Cheng Yeh

2014-01-01

Full Text Available Background: Whole slide imaging (WSI offers a novel approach to digitize and review pathology slides, but the voluminous data generated by this technology demand new computational methods for image analysis. Materials and Methods: In this study, we report a method that recognizes stains in WSI data and uses kernel density estimator to calculate the stain density across the digitized pathology slides. The validation study was conducted using a rat model of acute cardiac allograft rejection and another rat model of heart ischemia/reperfusion injury. Immunohistochemistry (IHC was conducted to label ED1 + macrophages in the tissue sections and the stained slides were digitized by a whole slide scanner. The whole slide images were tessellated to enable parallel processing. Pixel-wise stain classification was conducted to classify the IHC stains from those of the background and the density distribution of the identified IHC stains was then calculated by the kernel density estimator. Results: The regression analysis showed a correlation coefficient of 0.8961 between the number of IHC stains counted by our stain recognition algorithm and that by the manual counting, suggesting that our stain recognition algorithm was in good agreement with the manual counting. The density distribution of the IHC stains showed a consistent pattern with those of the cellular magnetic resonance (MR images that detected macrophages labeled by ultrasmall superparamagnetic iron-oxide or micron-sized iron-oxide particles. Conclusions: Our method provides a new imaging modality to facilitate clinical diagnosis. It also provides a way to validate/correlate cellular MRI data used for tracking immune-cell infiltration in cardiac transplant rejection and cardiac ischemic injury.

Interspecies comparison of the tissue distribution of WR-2721, a radioprotective drug

International Nuclear Information System (INIS)

Washburn, L.C.; Rafter, J.J.; Hayes, R.L.; Yuhas, J.M.

1975-01-01

Pre-irradiation intravenous administration of the radioprotective drug S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR-2721) has potential value in radiotherapy because it doubles the radiation resistance of normal mouse tissues while affording only minimal protection to tumors. Deficient deposition of WR- 2721 in tumor tissue has recently been demonstrated and this is thought to be a major reason for the preferential protection of normal tissues by the drug. Data originally obtained in studies using the mouse and rat indicated that the tissue distribution of WR-2721 was possibly more closely related to dose per unit surface area than to dose per unit weight. To test this hypothesis an interspecies comparison of the tissue distribution of 35 S-labeled WR-2721 was carried out in normal mice, rats, rabbits, and dogs at 15 and 30 minutes after intravenous administration. Results suggest that the surface area and body weight exert equal effects on the tissue concentration of WR-2721. The results further suggest that lower absolute doses of WR-2721 in the human, possibly as low as 20 mg/kg, may provide a radioprotective effect equivalent to that produced from 100 mg/kg in the mouse, i.e., a 50 to 80 percent increase in radiation resistance (CH)

An Attempt of Nondestructive Imaging of Sugar Distribution inside a Fruit Using Microwaves

Science.gov (United States)

Watanabe, Masakazu; Miyakawa, Michio

Chirp Pulse Microwave Computed Tomography (CP-MCT) that was originally developed for noninvasive imaging of a human body was applied to visualize sugar distribution inside a fruit. It can visualize not only permittivity distribution itself of a fruit but also various physical- or chemical-quantities relating to the permittivity value. Almost all fruits are dielectric materials containing much water, sugar, acids and so on. But for water, the principal ingredient of a fruit is sugar. Most of the fruits contain sugar from 8% to 22% by weight at the harvest time. Therefore sugar content distribution should be measured by CP-MCT nondestructively. By using apples and Japanese pears, feasibility of sugar distribution imaging has been evaluated by comparing the gray level of CP-MCT and sugar content of the cross section. The averaged correlation coefficients of the apple and pear are 0.793 and 0.681.

Feature Recognition of Froth Images Based on Energy Distribution Characteristics

Directory of Open Access Journals (Sweden)

WU Yanpeng

2014-09-01

Full Text Available This paper proposes a determining algorithm for froth image features based on the amplitude spectrum energy statistics by applying Fast Fourier Transformation to analyze the energy distribution of various-sized froth. The proposed algorithm has been used to do a froth feature analysis of the froth images from the alumina flotation processing site, and the results show that the consistency rate reaches 98.1 % and the usability rate 94.2 %; with its good robustness and high efficiency, the algorithm is quite suitable for flotation processing state recognition.

Persistent Drug-Induced Parkinsonism in Patients with Normal Dopamine Transporter Imaging.

Directory of Open Access Journals (Sweden)

Jin Yong Hong

Full Text Available Functional neuroimaging for the dopamine transporter (DAT is used to distinguish drug-induced parkinsonism (DIP from subclinical Parkinson's disease (PD. Although DIP patients who show a normal DAT image are expected to recover completely, some do not. We investigated whether these patients showed changes in striatal DAT activity using semi-quantitative analysis of 18F-FP-CIT PET data. DIP patients with visually normal DAT images were selected from medical records. The subjects were classified as patients who recovered partially (PR or completely within 12 months (CR. The 18F-FP-CIT uptake in each striatal subregion was compared between the CR and the PR groups. In total, 41 and 9 patients of the CR and PR groups were assessed, respectively. The two patient groups were comparable in terms of clinical characteristics including age, sex, and severity of parkinsonism. From semi-quantitative analysis of the PET image, the PR patients showed a relatively lower ligand uptake in the ventral striatum, the anterior putamen and the posterior putamen compared with the CR patients. This result suggests that persistent DIP in patients with visually normal DAT imaging may be associated with subtle decrement of DAT activity.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

Science.gov (United States)

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

Filmless reading and digital imaging distribution with refering to physicians

International Nuclear Information System (INIS)

Matzko, M.; Nissen-Meyer, S.; Sprenger, D.

1999-01-01

In healthcare, cost effectiveness as well as the quality of examinations and procedures are subjected to quickly increasing expectations and demands: We like to demonstrate how the resulting challenges and problems can be met with implementation of modern information technology. Analysing the respective demands (pattern of quantities) and choosing the adequate technical solution/ technical approach, we found filmless reading and the usage of digital image distribution to communicate with referring physicians to be cost effective as well as of higher quality. Special attention should be paid to the rigorous maintenance of data security and access. Today's information technology allows individual adjustment to the respective size and requirements of a radiological department or practice for filmless reading and digital image distribution. Working with the systems as a matter of routine and using all of the expanding technological possibilities, an important improvement of service and quality can be achieved. Amortisation will be obtained despite high investments, due to the subsequent savings in personal- and enterprise costs. (orig.) [de

Development of novel small molecules for imaging and drug release

Science.gov (United States)

Cao, Yanting

Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model

International Nuclear Information System (INIS)

Saito, Y.; Rubenstein, R.; Price, R.W.; Fox, J.J.; Watanabe, K.A.

1984-01-01

To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application

Luminescent GdVO4:Eu3+ functionalized mesoporous silica nanoparticles for magnetic resonance imaging and drug delivery.

Science.gov (United States)

Huang, Shanshan; Cheng, Ziyong; Ma, Ping'an; Kang, Xiaojiao; Dai, Yunlu; Lin, Jun

2013-05-14

Luminescent GdVO4:Eu(3+) nanophosphor functionalized mesoporous silica nanoparticles (MSN) were prepared (denoted as GdVO4:Eu(3+)@MSN). The in vitro cytotoxicity tests show that the sample has good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. Flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 ovarian cancer cells and A549 lung adenocarcinoma cells. It was also shown that the GdVO4:Eu(3+)@MSN brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. It was found that the carriers present a pH-dependent drug release behavior for doxorubicin (DOX). The composites show a red emission under UV irradiation due to the GdVO4:Eu(3+) nanophosphors. Furthermore, the PL intensity of the composite shows correlation with the cumulative release of DOX. These results suggest that the composite can potentially act as a multifunctional drug carrier system with luminescent tagging, MR imaging and pH-controlled release property for DOX.

Spatial distribution of nanocrystals imaged at the liquid-air interface

NARCIS (Netherlands)

Rijssel, J.; van der Linden, Marte; Meeldijk, J.D.; van Dijk-Moes, R.J.A.; Philipse, A.P.; Erné, B.H.

2013-01-01

The 3D distribution of nanocrystals at the liquid-air interface is imaged for the first time on a single-particle level by cryogenic electron tomography, revealing the equilibrium concentration profile from the interface to the bulk of the liquid. When the surface tension of the liquid is decreased,

Cylindrical SUV distribution model for detecting skin lesions in body trunk FDG-PET/CT images

International Nuclear Information System (INIS)

Nemoto, Mitsutaka; Nomura, Yukihiro; Masutani, Yoshitaka; Yoshikawa, Takeharu; Hayashi, Naoto; Yoshioka, Naoki; Ohtomo, Kuni; Hanaoka, Shouhei

2010-01-01

We have been developing a computerized detection method for skin lesions in body trunk fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT images. Spots on the skin with a high standard uptake value (SUV) are due not only to glucose metabolism in skin lesions but also to the physiological metabolism of organs near the skin. The distribution pattern of regional SUV on the skin is important information for the differential diagnosis of such high-SUV spots. In this study, we have developed a new skin lesion detection method based on a cylindrical SUV distribution model of the skin. The shape of the SUV distribution model is an approximation of the body trunk, and the SUV distribution model includes standard values for regional skin SUV. Classifier ensembles based on CT image features, SUV features, and subtraction features between the SUVs in FDG-PET images and the values in the SUV distribution model are used to extract and classify candidate regions for skin lesions. In a study of skin lesion detection using FDG-PET/CT images in 36 clinical cases, the true-positive rate was 61.7%, with 11.7 false-positive regions per case. The training results of the classifier ensemble for extracting and classifying candidate regions showed the effective features for detecting skin lesions in the study. (author)

Strategies to improve drug delivery across the blood-brain barrier.

Science.gov (United States)

de Boer, Albertus G; Gaillard, Pieter J

2007-01-01

The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

Distribution of a low dose compound within pharmaceutical tablet by using multivariate curve resolution on Raman hyperspectral images.

Science.gov (United States)

Boiret, Mathieu; de Juan, Anna; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

2015-01-25

In this work, Raman hyperspectral images and multivariate curve resolution-alternating least squares (MCR-ALS) are used to study the distribution of actives and excipients within a pharmaceutical drug product. This article is mainly focused on the distribution of a low dose constituent. Different approaches are compared, using initially filtered or non-filtered data, or using a column-wise augmented dataset before starting the MCR-ALS iterative process including appended information on the low dose component. In the studied formulation, magnesium stearate is used as a lubricant to improve powder flowability. With a theoretical concentration of 0.5% (w/w) in the drug product, the spectral variance contained in the data is weak. By using a principal component analysis (PCA) filtered dataset as a first step of the MCR-ALS approach, the lubricant information is lost in the non-explained variance and its associated distribution in the tablet cannot be highlighted. A sufficient number of components to generate the PCA noise-filtered matrix has to be used in order to keep the lubricant variability within the data set analyzed or, otherwise, work with the raw non-filtered data. Different models are built using an increasing number of components to perform the PCA reduction. It is shown that the magnesium stearate information can be extracted from a PCA model using a minimum of 20 components. In the last part, a column-wise augmented matrix, including a reference spectrum of the lubricant, is used before starting MCR-ALS process. PCA reduction is performed on the augmented matrix, so the magnesium stearate contribution is included within the MCR-ALS calculations. By using an appropriate PCA reduction, with a sufficient number of components, or by using an augmented dataset including appended information on the low dose component, the distribution of the two actives, the two main excipients and the low dose lubricant are correctly recovered. Copyright © 2014 Elsevier B

Spatial Data Exploring by Satellite Image Distributed Processing

Science.gov (United States)

Mihon, V. D.; Colceriu, V.; Bektas, F.; Allenbach, K.; Gvilava, M.; Gorgan, D.

2012-04-01

Our society needs and environmental predictions encourage the applications development, oriented on supervising and analyzing different Earth Science related phenomena. Satellite images could be explored for discovering information concerning land cover, hydrology, air quality, and water and soil pollution. Spatial and environment related data could be acquired by imagery classification consisting of data mining throughout the multispectral bands. The process takes in account a large set of variables such as satellite image types (e.g. MODIS, Landsat), particular geographic area, soil composition, vegetation cover, and generally the context (e.g. clouds, snow, and season). All these specific and variable conditions require flexible tools and applications to support an optimal search for the appropriate solutions, and high power computation resources. The research concerns with experiments on solutions of using the flexible and visual descriptions of the satellite image processing over distributed infrastructures (e.g. Grid, Cloud, and GPU clusters). This presentation highlights the Grid based implementation of the GreenLand application. The GreenLand application development is based on simple, but powerful, notions of mathematical operators and workflows that are used in distributed and parallel executions over the Grid infrastructure. Currently it is used in three major case studies concerning with Istanbul geographical area, Rioni River in Georgia, and Black Sea catchment region. The GreenLand application offers a friendly user interface for viewing and editing workflows and operators. The description involves the basic operators provided by GRASS [1] library as well as many other image related operators supported by the ESIP platform [2]. The processing workflows are represented as directed graphs giving the user a fast and easy way to describe complex parallel algorithms, without having any prior knowledge of any programming language or application commands

Fluorescence imaging of ion distributions in an inductively coupled plasma with laser ablation sample introduction

International Nuclear Information System (INIS)

Moses, Lance M.; Ellis, Wade C.; Jones, Derick D.; Farnsworth, Paul B.

2015-01-01

High-resolution images of the spatial distributions of Sc II, Ca II, and Ba II ion densities in the 10 mm upstream from the sampling cone in a laser ablation-inductively coupled plasma-mass spectrometer (LA-ICP-MS) were obtained using planar laser induced fluorescence. Images were obtained for each analyte as a function of the carrier gas flow rate with laser ablation (LA) sample introduction and compared to images with solution nebulization (SN) over the same range of flow rates. Additionally, images were obtained using LA at varying fluences and with varying amounts of helium added to a constant flow of argon gas. Ion profiles in SN images followed a pattern consistent with previous work: increasing gas flow caused a downstream shift in the ion profiles. When compared to SN, LA led to ion profiles that were much narrower radially and reached a maximum near the sampling cone at higher flow rates. Increasing the fluence led to ions formed in the ICP over greater axial and radial distances. The addition of He to the carrier gas prior to the ablation cell led to an upstream shift in the position of ionization and lower overall fluorescence intensities. - Highlights: • We map distributions of analytes in the ICP using laser ablation sample introduction. • We compare images from laser ablation with those from a pneumatic nebulizer. • We document the effects of water added to the laser ablation aerosol. • We compare distributions from a metal to those from crystalline solids. • We document the effect of laser fluence on ion distributions

Evaluation of moisture content distribution in wood by soft X-ray imaging

International Nuclear Information System (INIS)

Tanaka, T.; Avramidis, S.; Shida, S.

2009-01-01

A technique for nondestructive evaluation of moisture content distribution of Japanese cedar (sugi) during drying using a newly developed soft X-ray digital microscope was investigated. Radial, tangential, and cross-sectional samples measuring 100 x 100 x 10 mm were cut from green sugi wood. Each sample was dried in several steps in an oven and upon completion of each step, the mass was recorded and a soft X-ray image was taken. The relationship between moisture content and the average grayscale value of the soft X-ray image at each step was linear. In addition, the linear regressions overlapped each other regardless of the sample sections. These results showed that soft X-ray images could accurately estimate the moisture content. Applying this relationship to a small section of each sample, the moisture content distribution was estimated from the image differential between the soft X-ray pictures obtained from the sample in question and the same sample in the oven-dried condition. Moisture content profiles for 10-mm-wide parts at the centers of the samples were also obtained. The shapes of the profiles supported the evaluation method used in this study

Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart.

Science.gov (United States)

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; Zhou, Zhaoye; He, Bin

2013-10-01

Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine. To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits. Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates. The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites. The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis. © 2013 Heart Rhythm Society. All rights reserved.

41 CFR 105-74.210 - To whom must I distribute my drug-free workplace statement?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false To whom must I distribute my drug-free workplace statement? 105-74.210 Section 105-74.210 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION...

A simple algorithm for measuring particle size distributions on an uneven background from TEM images

DEFF Research Database (Denmark)

Gontard, Lionel Cervera; Ozkaya, Dogan; Dunin-Borkowski, Rafal E.

2011-01-01

Nanoparticles have a wide range of applications in science and technology. Their sizes are often measured using transmission electron microscopy (TEM) or X-ray diffraction. Here, we describe a simple computer algorithm for measuring particle size distributions from TEM images in the presence of a...... application to images of heterogeneous catalysts is presented.......Nanoparticles have a wide range of applications in science and technology. Their sizes are often measured using transmission electron microscopy (TEM) or X-ray diffraction. Here, we describe a simple computer algorithm for measuring particle size distributions from TEM images in the presence...

Mass distribution of fission fragments using SSNTDs based image analysis system

International Nuclear Information System (INIS)

Kolekar, R.V.; Sharma, D.N.

2006-01-01

Lexan polycarbonate track detector was used to obtain mass distribution of fission fragments from 252 Cf planchette source, Normally, if the fission fragments are incident perpendicular to the lexan surface, the diameter of heavy fragment is greater than that of lighter fragment. In practical problems fission fragments are incident on the detector at all angles. So, in the present experiment, lexan detector was exposed to 252 Cf planchette source in 2π geometry. Fission fragments were incident on the detector with various angles. So the projected fission track length for fission fragment of same energy is different because of different angle of incidence. Image analysis software was used to measure the projected track length. But the problem is that for fission fragment having greater angle of incidence the entire track length is not focused on the surface. So reduced track length is measured. This problem is solved by taking two images, one at the surface and one at the tip of track and then overlapping both the images using image analysis software. The projected track length and the depth of the track were used to get the angle of incidence. Fission track lengths were measured for same angle of incidence. In all 500 track lengths were measured and plot for mass distribution for fission fragment was obtained.(author)

A possible application of magnetic resonance imaging for pharmaceutical research.

Science.gov (United States)

Kowalczuk, Joanna; Tritt-Goc, Jadwiga

2011-03-18

Magnetic resonance imaging (MRI) is a non-destructive and non-invasive method, the experiment can be conducted in situ and allows the studying of the sample and the different processes in vitro or in vivo. 1D, 2D or 3D imaging can be undertaken. MRI is nowadays most widely used in medicine as a clinical diagnostic tool, but has still seen limited application in the food and pharmaceutical sciences. The different imaging pulse sequences of MRI allow to image the processes that take place in a wide scale range from ms (dissolution of compact tablets) to hours (hydration of drug delivery systems) for mobile as well as for rigid spins, usually protons. The paper gives examples of MRI application of in vitro imaging of pharmaceutical dosage based on hydroxypropyl methylcellulose which have focused on water-penetration, diffusion, polymer swelling, and drug release, characterized with respect to other physical parameters such as pH and the molecular weight of polymer. Tetracycline hydrochloride was used as a model drug. NMR imaging of density distributions and fast kinetics of the dissolution behavior of compact tablets is presented for paracetamol tablets. Copyright © 2010 Elsevier B.V. All rights reserved.

Distribution quantification on dermoscopy images for computer-assisted diagnosis of cutaneous melanomas.

Science.gov (United States)

Liu, Zhao; Sun, Jiuai; Smith, Lyndon; Smith, Melvyn; Warr, Robert

2012-05-01

Computerised analysis on skin lesion images has been reported to be helpful in achieving objective and reproducible diagnosis of melanoma. In particular, asymmetry in shape, colour and structure reflects the irregular growth of melanin under the skin and is of great importance for diagnosing the malignancy of skin lesions. This paper proposes a novel asymmetry analysis based on a newly developed pigmentation elevation model and the global point signatures (GPSs). Specifically, the pigmentation elevation model was first constructed by computer-based analysis of dermoscopy images, for the identification of melanin and haemoglobin. Asymmetry of skin lesions was then assessed through quantifying distributions of the pigmentation elevation model using the GPSs, derived from a Laplace-Beltrami operator. This new approach allows quantifying the shape and pigmentation distributions of cutaneous lesions simultaneously. Algorithm performance was tested on 351 dermoscopy images, including 88 malignant melanomas and 263 benign naevi, employing a support vector machine (SVM) with tenfold cross-validation strategy. Competitive diagnostic results were achieved using the proposed asymmetry descriptor only, presenting 86.36 % sensitivity, 82.13 % specificity and overall 83.43 % accuracy, respectively. In addition, the proposed GPS-based asymmetry analysis enables working on dermoscopy images from different databases and is approved to be inherently robust to the external imaging variations. These advantages suggested that the proposed method has good potential for follow-up treatment.

Organic-Inorganic Hybrid Hollow Mesoporous Organosilica Nanoparticles for Efficient Ultrasound-Based Imaging and Controlled Drug Release

Directory of Open Access Journals (Sweden)

Xiaoqin Qian

2014-01-01

Full Text Available A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs. The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography both in vitro and in vivo and can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX- loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higher in vitro and in vivo tumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

Architecture of distributed picture archiving and communication systems for storing and processing high resolution medical images

Science.gov (United States)

Tokareva, Victoria

2018-04-01

New generation medicine demands a better quality of analysis increasing the amount of data collected during checkups, and simultaneously decreasing the invasiveness of a procedure. Thus it becomes urgent not only to develop advanced modern hardware, but also to implement special software infrastructure for using it in everyday clinical practice, so-called Picture Archiving and Communication Systems (PACS). Developing distributed PACS is a challenging task for nowadays medical informatics. The paper discusses the architecture of distributed PACS server for processing large high-quality medical images, with respect to technical specifications of modern medical imaging hardware, as well as international standards in medical imaging software. The MapReduce paradigm is proposed for image reconstruction by server, and the details of utilizing the Hadoop framework for this task are being discussed in order to provide the design of distributed PACS as ergonomic and adapted to the needs of end users as possible.

Method of synthesis of abstract images with high self-similarity

Science.gov (United States)

Matveev, Nikolay V.; Shcheglov, Sergey A.; Romanova, Galina E.; Koneva, Ð.¢atiana A.

2017-06-01

Abstract images with high self-similarity could be used for drug-free stress therapy. This based on the fact that a complex visual environment has a high affective appraisal. To create such an image we can use the setup based on the three laser sources of small power and different colors (Red, Green, Blue), the image is the pattern resulting from the reflecting and refracting by the complicated form object placed into the laser ray paths. The images were obtained experimentally which showed the good therapy effect. However, to find and to choose the object which gives needed image structure is very difficult and requires many trials. The goal of the work is to develop a method and a procedure of finding the object form which if placed into the ray paths can provide the necessary structure of the image In fact the task means obtaining the necessary irradiance distribution on the given surface. Traditionally such problems are solved using the non-imaging optics methods. In the given case this task is very complicated because of the complicated structure of the illuminance distribution and its high non-linearity. Alternative way is to use the projected image of a mask with a given structure. We consider both ways and discuss how they can help to speed up the synthesis procedure for the given abstract image of the high self-similarity for the setups of drug-free therapy.

Integration of piezo-capacitive and piezo-electric nanoweb based pressure sensors for imaging of static and dynamic pressure distribution.

Science.gov (United States)

Jeong, Y J; Oh, T I; Woo, E J; Kim, K J

2017-07-01

Recently, highly flexible and soft pressure distribution imaging sensor is in great demand for tactile sensing, gait analysis, ubiquitous life-care based on activity recognition, and therapeutics. In this study, we integrate the piezo-capacitive and piezo-electric nanowebs with the conductive fabric sheets for detecting static and dynamic pressure distributions on a large sensing area. Electrical impedance tomography (EIT) and electric source imaging are applied for reconstructing pressure distribution images from measured current-voltage data on the boundary of the hybrid fabric sensor. We evaluated the piezo-capacitive nanoweb sensor, piezo-electric nanoweb sensor, and hybrid fabric sensor. The results show the feasibility of static and dynamic pressure distribution imaging from the boundary measurements of the fabric sensors.

Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

Science.gov (United States)

Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

2016-03-14

Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

Tailored beads made of dissolved cellulose - Investigation of their drug release properties

DEFF Research Database (Denmark)

Yildir, Emrah; Kolakovic, Ruzica; Genina, Natalja

2013-01-01

In the frame of this work, we have investigated drug entrapping and release abilities of new type of porous cellulose beads (CBs) as a spherical matrix system for drug delivery. For that purpose, CBs prepared with three different methods were used as drug carriers and three compounds, anhydrous...... theophylline (Thp), riboflavin 5′-phosphate sodium (RSP) and lidocaine hydrochloride monohydrate (LiHCl) were used as model drug substances. The loading procedure was carried out by immersing swollen empty beads into the solutions of different concentrations of model drugs. The morphology of empty and loaded...... beads was examined using a field emission scanning electron microscopy (FE-SEM). Near-infrared (NIR) imaging was performed to identify the drug distributions on and within the loaded CBs. The drug amount incorporated into CBs was examined spectrophotometrically and in vitro drug release studies were...

Weighting training images by maximizing distribution similarity for supervised segmentation across scanners

DEFF Research Database (Denmark)

van Opbroek, Annegreet; Vernooij, Meike W; Ikram, M.Arfan

2015-01-01

Many automatic segmentation methods are based on supervised machine learning. Such methods have proven to perform well, on the condition that they are trained on a sufficiently large manually labeled training set that is representative of the images to segment. However, due to differences between...... scanners, scanning parameters, and patients such a training set may be difficult to obtain. We present a transfer-learning approach to segmentation by multi-feature voxelwise classification. The presented method can be trained using a heterogeneous set of training images that may be obtained with different...... scanners than the target image. In our approach each training image is given a weight based on the distribution of its voxels in the feature space. These image weights are chosen as to minimize the difference between the weighted probability density function (PDF) of the voxels of the training images...

Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia

Directory of Open Access Journals (Sweden)

Nestorovska Kapedanovska A.

2014-12-01

Full Text Available Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response.

Optical cryptography topology based on a three-dimensional particle-like distribution and diffractive imaging.

Science.gov (United States)

Chen, Wen; Chen, Xudong

2011-05-09

In recent years, coherent diffractive imaging has been considered as a promising alternative for information retrieval instead of conventional interference methods. Coherent diffractive imaging using the X-ray light source has opened up a new research perspective for the measurement of non-crystalline and biological specimens, and can achieve unprecedentedly high resolutions. In this paper, we show how a three-dimensional (3D) particle-like distribution and coherent diffractive imaging can be applied for a study of optical cryptography. An optical multiple-random-phase-mask encoding approach is used, and the plaintext is considered as a series of particles distributed in a 3D space. A topology concept is also introduced into the proposed optical cryptosystem. During image decryption, a retrieval algorithm is developed to extract the plaintext from the ciphertexts. In addition, security and advantages of the proposed optical cryptography topology are also analyzed. © 2011 Optical Society of America

Process and installation for producing tomographic images of the distribution of a radiotracer

International Nuclear Information System (INIS)

Fonroget, Jacques; Brunol, Jean.

1977-01-01

The invention particularly concerns a process for obtaining tomographic images of an object formed by a radiotracer distributed spacially over three dimensions. This process, using a detection device with an appreciably plane detection surface and at least one collimation orifice provided in a partition between the detection surface and the object, enables tomographic sections to be obtained with an excellent three-dimensional resolution of the images achieved. It is employed to advantage in an installation that includes a detection device or gamma camera on an appreciably plane surface, a device having a series of collimation apertures which may be used in succession, these holes being appreciably distributed over a common plane parallel to the detection surface, and a holder for the object. This holder can be moved in appreciably parallel translation to the common plane. The aim of this invention is, inter alia, to meet two requirements: localization in space and obtaining good contrasts. This aim is achieved by the fact that at least one tomographic image is obtained from a series of intermediate images of the object [fr

Exploring the relationship between online buyers and sellers of image and performance enhancing drugs (IPEDs): Quality issues, trust and self-regulation

NARCIS (Netherlands)

van de Ven, K.; Koenraadt, R.M.

2017-01-01

Background Online drug markets are expanding the boundaries of drug supply including the sale and purchase of image and performance enhancing drugs (IPEDs). However, the role of the internet in IPED markets, and in particular the ways in which these substances are supplied via the surface web, has

Visualizing metabolite distribution and enzymatic conversion in plant tissues by desorption electrospray ionization mass spectrometry imaging

DEFF Research Database (Denmark)

Li, Bin; Baden, Camilla Knudsen; Hansen, Natascha Kristine Krahl

2013-01-01

In comparison to the technology platforms developed to localize transcripts and proteins, imaging tools for visualization of metabolite distributions in plant tissues are less well developed and lack versatility. This hampers our understanding of plant metabolism and dynamics. In this study we...... demonstrate that Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) of tissue imprints on porous Teflon can be used to accurately image the distribution of even labile plant metabolites such as hydroxynitrile glucosides, which normally undergo enzymatic hydrolysis by specific ß......-glucosidases upon cell disruption. This fast and simple sample preparation resulted in no substantial differences in the distribution and ratios of all hydroxynitrile glucosides between leaves from wildtype Lotus japonicus and a ß-glucosidase mutant plant lacking the ability to hydrolyze certain hydroxynitrile...

Difet: Distributed Feature Extraction Tool for High Spatial Resolution Remote Sensing Images

Science.gov (United States)

Eken, S.; Aydın, E.; Sayar, A.

2017-11-01

In this paper, we propose distributed feature extraction tool from high spatial resolution remote sensing images. Tool is based on Apache Hadoop framework and Hadoop Image Processing Interface. Two corner detection (Harris and Shi-Tomasi) algorithms and five feature descriptors (SIFT, SURF, FAST, BRIEF, and ORB) are considered. Robustness of the tool in the task of feature extraction from LandSat-8 imageries are evaluated in terms of horizontal scalability.

The effect of nanoparticle size on theranostic systems: the optimal particle size for imaging is not necessarily optimal for drug delivery

Science.gov (United States)

Dreifuss, Tamar; Betzer, Oshra; Barnoy, Eran; Motiei, Menachem; Popovtzer, Rachela

2018-02-01

Theranostics is an emerging field, defined as combination of therapeutic and diagnostic capabilities in the same material. Nanoparticles are considered as an efficient platform for theranostics, particularly in cancer treatment, as they offer substantial advantages over both common imaging contrast agents and chemotherapeutic drugs. However, the development of theranostic nanoplatforms raises an important question: Is the optimal particle for imaging also optimal for therapy? Are the specific parameters required for maximal drug delivery, similar to those required for imaging applications? Herein, we examined this issue by investigating the effect of nanoparticle size on tumor uptake and imaging. Anti-epidermal growth factor receptor (EGFR)-conjugated gold nanoparticles (GNPs) in different sizes (diameter range: 20-120 nm) were injected to tumor bearing mice and their uptake by tumors was measured, as well as their tumor visualization capabilities as tumor-targeted CT contrast agent. Interestingly, the results showed that different particles led to highest tumor uptake or highest contrast enhancement, meaning that the optimal particle size for drug delivery is not necessarily optimal for tumor imaging. These results have important implications on the design of theranostic nanoplatforms.

Experimental validation of the Wigner distributions theory of phase-contrast imaging

International Nuclear Information System (INIS)

Donnelly, Edwin F.; Price, Ronald R.; Pickens, David R.

2005-01-01

Recently, a new theory of phase-contrast imaging has been proposed by Wu and Liu [Med. Phys. 31, 2378-2384 (2004)]. This theory, based upon Wigner distributions, provides a much stronger foundation for the evaluation of phase-contrast imaging systems than did the prior theories based upon Fresnel-Kirchhoff diffraction theory. In this paper, we compare results of measurements made in our laboratory of phase contrast for different geometries and tube voltages to the predictions of the Wu and Liu model. In our previous publications, we have used an empirical measurement (the edge enhancement index) to parametrize the degree of phase-contrast effects in an image. While the Wu and Liu model itself does not predict image contrast, it does measure the degree of phase contrast that the system can image for a given spatial frequency. We have found that our previously published experimental results relating phase-contrast effects to geometry and x-ray tube voltage are consistent with the predictions of the Wu and Liu model

Imaging of current distributions in superconducting thin film structures; Abbildung von Stromverteilungen in supraleitenden Duennfilmstrukturen

Energy Technology Data Exchange (ETDEWEB)

Doenitz, D.

2006-10-31

Local analysis plays an important role in many fields of scientific research. However, imaging methods are not very common in the investigation of superconductors. For more than 20 years, Low Temperature Scanning Electron Microscopy (LTSEM) has been successfully used at the University of Tuebingen for studying of condensed matter phenomena, especially of superconductivity. In this thesis LTSEM was used for imaging current distributions in different superconducting thin film structures: - Imaging of current distributions in Josephson junctions with ferromagnetic interlayer, also known as SIFS junctions, showed inhomogeneous current transport over the junctions which directly led to an improvement in the fabrication process. An investigation of improved samples showed a very homogeneous current distribution without any trace of magnetic domains. Either such domains were not present or too small for imaging with the LTSEM. - An investigation of Nb/YBCO zigzag Josephson junctions yielded important information on signal formation in the LTSEM both for Josephson junctions in the short and in the long limit. Using a reference junction our signal formation model could be verified, thus confirming earlier results on short zigzag junctions. These results, which could be reproduced in this work, support the theory of d-wave symmetry in the superconducting order parameter of YBCO. Furthermore, investigations of the quasiparticle tunneling in the zigzag junctions showed the existence of Andreev bound states, which is another indication of the d-wave symmetry in YBCO. - The LTSEM study of Hot Electron Bolometers (HEB) allowed the first successful imaging of a stable 'Hot Spot', a self-heating region in HEB structures. Moreover, the electron beam was used to induce an - otherwise unstable - hot spot. Both investigations yielded information on the homogeneity of the samples. - An entirely new method of imaging the current distribution in superconducting interference

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes

International Nuclear Information System (INIS)

Mohan, Radhe; Zhang Xiaodong; Wang He; Kang Yixiu; Wang Xiaochun; Liu, Helen; Ang, K.; Kuban, Deborah; Dong Lei

2005-01-01

Purpose: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. Methods and materials: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam

A custom-built PET phantom design for quantitative imaging of printed distributions

International Nuclear Information System (INIS)

Markiewicz, P J; Angelis, G I; Kotasidis, F; Green, M; Matthews, J C; Lionheart, W R; Reader, A J

2011-01-01

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)

Measurement of heterogeneous distribution on technegas SPECT images by three-dimensional fractal analysis

International Nuclear Information System (INIS)

Nagao, Michinobu; Murase, Kenya

2002-01-01

This review article describes a method for quantifying heterogeneous distribution on Technegas ( 99m Tc-carbon particle radioaerosol) SPECT images by three-dimensional fractal analysis (3D-FA). Technegas SPECT was performed to quantify the severity of pulmonary emphysema. We delineated the SPECT images by using five cut-offs (15, 20, 25, 30 and 35% of the maximal voxel radioactivity), and measured the total number of voxels in the areas surrounded by the contours obtained with each cut-off level. We calculated fractal dimensions from the relationship between the total number of voxels and the cut-off levels transformed into natural logarithms. The fractal dimension derived from 3D-FA is the relative and objective measurement, which can assess the heterogeneous distribution on Technegas SPECT images. The fractal dimension strongly correlate pulmonary function in patients with emphysema and well documented the overall and regional severity of emphysema. (author)

Architecture of distributed picture archiving and communication systems for storing and processing high resolution medical images

Directory of Open Access Journals (Sweden)

Tokareva Victoria

2018-01-01

Full Text Available New generation medicine demands a better quality of analysis increasing the amount of data collected during checkups, and simultaneously decreasing the invasiveness of a procedure. Thus it becomes urgent not only to develop advanced modern hardware, but also to implement special software infrastructure for using it in everyday clinical practice, so-called Picture Archiving and Communication Systems (PACS. Developing distributed PACS is a challenging task for nowadays medical informatics. The paper discusses the architecture of distributed PACS server for processing large high-quality medical images, with respect to technical specifications of modern medical imaging hardware, as well as international standards in medical imaging software. The MapReduce paradigm is proposed for image reconstruction by server, and the details of utilizing the Hadoop framework for this task are being discussed in order to provide the design of distributed PACS as ergonomic and adapted to the needs of end users as possible.

From PACS to Web-based ePR system with image distribution for enterprise-level filmless healthcare delivery.

Science.gov (United States)

Huang, H K

2011-07-01

The concept of PACS (picture archiving and communication system) was initiated in 1982 during the SPIE medical imaging conference in New Port Beach, CA. Since then PACS has been matured to become an everyday clinical tool for image archiving, communication, display, and review. This paper follows the continuous development of PACS technology including Web-based PACS, PACS and ePR (electronic patient record), enterprise PACS to ePR with image distribution (ID). The concept of large-scale Web-based enterprise PACS and ePR with image distribution is presented along with its implementation, clinical deployment, and operation. The Hong Kong Hospital Authority's (HKHA) integration of its home-grown clinical management system (CMS) with PACS and ePR with image distribution is used as a case study. The current concept and design criteria of the HKHA enterprise integration of the CMS, PACS, and ePR-ID for filmless healthcare delivery are discussed, followed by its work-in-progress and current status.

Quantitative Analysis of Subcellular Distribution of the SUMO Conjugation System by Confocal Microscopy Imaging.

Science.gov (United States)

Mas, Abraham; Amenós, Montse; Lois, L Maria

2016-01-01

Different studies point to an enrichment in SUMO conjugation in the cell nucleus, although non-nuclear SUMO targets also exist. In general, the study of subcellular localization of proteins is essential for understanding their function within a cell. Fluorescence microscopy is a powerful tool for studying subcellular protein partitioning in living cells, since fluorescent proteins can be fused to proteins of interest to determine their localization. Subcellular distribution of proteins can be influenced by binding to other biomolecules and by posttranslational modifications. Sometimes these changes affect only a portion of the protein pool or have a partial effect, and a quantitative evaluation of fluorescence images is required to identify protein redistribution among subcellular compartments. In order to obtain accurate data about the relative subcellular distribution of SUMO conjugation machinery members, and to identify the molecular determinants involved in their localization, we have applied quantitative confocal microscopy imaging. In this chapter, we will describe the fluorescent protein fusions used in these experiments, and how to measure, evaluate, and compare average fluorescence intensities in cellular compartments by image-based analysis. We show the distribution of some components of the Arabidopsis SUMOylation machinery in epidermal onion cells and how they change their distribution in the presence of interacting partners or even when its activity is affected.

Mapping the subcellular distribution of biomolecules at the ultrastructural level by ion microscopy.

Science.gov (United States)

Galle, P; Escaig, F; Dantin, F; Zhang, L

1996-05-01

Analytical ion microscopy, a method proposed and developed in 1960 by Casting and Slodzian at the Orsay University (France), makes it possible to obtain easily and rapidly analytical images representing the distribution in a tissue section of elements or isotopes (beginning from the three isotopes of hydrogen until to transuranic elements), even when these elements or isotopes are at a trace concentration of 1 ppm or less. This method has been applied to study the subcellular distribution of different varieties of biomolecules. The subcellular location of these molecules can be easily determined when the molecules contain in their structures a specific atom such as fluorine, iodine, bromine or platinum, what is the case of many pharmaceutical drugs. In this situation, the distribution of these specific atoms can be considered as representative of the distribution of the corresponding molecule. In other cases, the molecules must be labelled with an isotope which may be either radioactive or stable. Recent developments in ion microscopy allow the obtention of their chemical images at ultra structural level. In this paper we present the results obtained with the prototype of a new Scanning Ion Microscope used for the study of the intracellular distribution of different varieties of molecules: glucocorticoids, estrogens, pharmaceutical drugs and pyrimidine analogues.

Realization of a video-rate distributed aperture millimeter-wave imaging system using optical upconversion

Science.gov (United States)

Schuetz, Christopher; Martin, Richard; Dillon, Thomas; Yao, Peng; Mackrides, Daniel; Harrity, Charles; Zablocki, Alicia; Shreve, Kevin; Bonnett, James; Curt, Petersen; Prather, Dennis

2013-05-01

Passive imaging using millimeter waves (mmWs) has many advantages and applications in the defense and security markets. All terrestrial bodies emit mmW radiation and these wavelengths are able to penetrate smoke, fog/clouds/marine layers, and even clothing. One primary obstacle to imaging in this spectrum is that longer wavelengths require larger apertures to achieve the resolutions desired for many applications. Accordingly, lens-based focal plane systems and scanning systems tend to require large aperture optics, which increase the achievable size and weight of such systems to beyond what can be supported by many applications. To overcome this limitation, a distributed aperture detection scheme is used in which the effective aperture size can be increased without the associated volumetric increase in imager size. This distributed aperture system is realized through conversion of the received mmW energy into sidebands on an optical carrier. This conversion serves, in essence, to scale the mmW sparse aperture array signals onto a complementary optical array. The side bands are subsequently stripped from the optical carrier and recombined to provide a real time snapshot of the mmW signal. Using this technique, we have constructed a real-time, video-rate imager operating at 75 GHz. A distributed aperture consisting of 220 upconversion channels is used to realize 2.5k pixels with passive sensitivity. Details of the construction and operation of this imager as well as field testing results will be presented herein.

DIFET: DISTRIBUTED FEATURE EXTRACTION TOOL FOR HIGH SPATIAL RESOLUTION REMOTE SENSING IMAGES

Directory of Open Access Journals (Sweden)

S. Eken

2017-11-01

Full Text Available In this paper, we propose distributed feature extraction tool from high spatial resolution remote sensing images. Tool is based on Apache Hadoop framework and Hadoop Image Processing Interface. Two corner detection (Harris and Shi-Tomasi algorithms and five feature descriptors (SIFT, SURF, FAST, BRIEF, and ORB are considered. Robustness of the tool in the task of feature extraction from LandSat-8 imageries are evaluated in terms of horizontal scalability.

Chitosan-Gated Magnetic-Responsive Nanocarrier for Dual-Modal Optical Imaging, Switchable Drug Release, and Synergistic Therapy

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Mu, Qingxin [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Revia, Richard [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Wang, Kui [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Zhou, Xuezhe [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Pauzauskie, Peter J. [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland WA 99354 USA; Zhou, Shuiqin [Department of Chemistry, The College of Staten Island, City University of New York, Staten Island NY 10314 USA; Zhang, Miqin [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA

2017-01-25

In this study, we present a multifunctional yet structurally simple nanocarrier that has a high drug loading capacity, releases drug in response to onset of an AC magnetic field, and can serve as a long-term imaging contrast agent and effectively kills cancer cells by synergistic action. This nanocarrier (HMMC-NC) has a spherical shell structure with a center cavity of 80 nm in diameter. The shell is comprised of two layers: an inner layer of magnetite that exhibits superparamagnetism and an outer layer of mesoporous carbon embedded with carbon dots that exhibit photoluminescence property. Thus in addition to being a drug carrier, HMMC-NC is also a contrast agent for bioimaging. The switchable drug release is enabled by the chitosan molecules attached on the nanocarrier as the switching material which turns on or off the drug release in response to the application or withdrawal of an AC magnetic field.

Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery.

Science.gov (United States)

Filho, Walter Duarte de Araujo; Schneider, Fábio Kurt; Morales, Rigoberto E M

2012-09-20

Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step. A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters. The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase. The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical applications even when regular air is used as the gas phase. Improved

Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery

Directory of Open Access Journals (Sweden)

Filho WalterDuartedeAraujo

2012-09-01

Full Text Available Abstract Background Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step. Methods A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters. Results The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase. Conclusion The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical

Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype

International Nuclear Information System (INIS)

Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

2006-01-01

The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues

Overdose prevention for injection drug users: lessons learned from naloxone training and distribution programs in New York City.

Science.gov (United States)

Piper, Tinka Markham; Rudenstine, Sasha; Stancliff, Sharon; Sherman, Susan; Nandi, Vijay; Clear, Allan; Galea, Sandro

2007-01-25

Fatal heroin overdose is a significant cause of mortality for injection drug users (IDUs). Many of these deaths are preventable because opiate overdoses can be quickly and safely reversed through the injection of Naloxone [brand name Narcan], a prescription drug used to revive persons who have overdosed on heroin or other opioids. Currently, in several cities in the United States, drug users are being trained in naloxone administration and given naloxone for immediate and successful reversals of opiate overdoses. There has been very little formal description of the challenges faced in the development and implementation of large-scale IDU naloxone administration training and distribution programs and the lessons learned during this process. During a one year period, over 1,000 participants were trained in SKOOP (Skills and Knowledge on Opiate Prevention) and received a prescription for naloxone by a medical doctor on site at a syringe exchange program (SEP) in New York City. Participants in SKOOP were over the age of 18, current participants of SEPs, and current or former drug users. We present details about program design and lessons learned during the development and implementation of SKOOP. Lessons learned described in the manuscript are collectively articulated by the evaluators and implementers of the project. There were six primary challenges and lessons learned in developing, implementing, and evaluating SKOOP. These include a) political climate surrounding naloxone distribution; b) extant prescription drug laws; c) initial low levels of recruitment into the program; d) development of participant appropriate training methodology; e) challenges in the design of a suitable formal evaluation; and f) evolution of program response to naloxone. Other naloxone distribution programs may anticipate similar challenges to SKOOP and we identify mechanisms to address them. Strategies include being flexible in program planning and implementation, developing evaluation

Clinical features and {sup 123}I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Sanz-Viedma, Salome [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Garcia-Solis, David [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, Pablo [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Hospital Universitario Virgen del Rocio, Unidad de Trastornos del Movimiento. Servicio de Neurologia, Seville (Spain)

2010-03-15

To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by {sup 123}I-FP-CIT SPECT imaging. (orig.)

Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

Directory of Open Access Journals (Sweden)

Youcef M. Rustum

2010-01-01

Full Text Available Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.

Analysis of pharmaceutical pellets: An approach using near-infrared chemical imaging

International Nuclear Information System (INIS)

Sabin, Guilherme P.; Breitkreitz, Marcia C.; Souza, Andre M. de; Fonseca, Patricia da; Calefe, Lupercio; Moffa, Mario; Poppi, Ronei J.

2011-01-01

Highlights: → Near-Infrared Chemical Imaging was used for pellets analysis. → Distribution of the components throughout the coatings layers and core of the pellets was estimated. → Classical Least Squares (CLS) was used for calculation of the concentration maps. - Abstract: Pharmaceutical pellets are spherical or nearly spherical multi-unit dosage forms designed to optimize pharmacokinetics and pharmacodynamics features of drug release. The distribution of the pharmaceutical ingredients in the layers and core is a very important parameter for appropriate drug release, especially for pellets manufactured by the process of layer gain. Physical aspects of the sample are normally evaluated by Scanning Electron Microscopy (SEM), but it is in many cases unsuitable to provide conclusive chemical information about the distribution of the pharmaceutical ingredients in both layers and core. On the other hand, methods based on spectroscopic imaging can be very promising for this purpose. In this work, a Near-Infrared Chemical Imaging (NIR-CI) method was developed and applied to the analysis of diclophenac sodium pellets. Since all the compounds present in the sample were known in advance, Classical Least Squares (CLS) was used for calculations. The results have shown that the method was capable of providing chemical information about the distribution of the active ingredient and excipients in the core and coating layers and therefore can be complementary to SEM for the pharmaceutical development of pellets.

Analysis of pharmaceutical pellets: An approach using near-infrared chemical imaging

Energy Technology Data Exchange (ETDEWEB)

Sabin, Guilherme P.; Breitkreitz, Marcia C.; Souza, Andre M. de [Institute of Chemistry, University of Campinas, P.O. Box 6154, 13084-971 Campinas, SP (Brazil); Fonseca, Patricia da; Calefe, Lupercio; Moffa, Mario [Zelus Servicos para Industria Farmaceutica Ltda., Av. Professor Lineu Prestes n. 2242, Sao Paulo, SP (Brazil); Poppi, Ronei J., E-mail: ronei@iqm.unicamp.br [Institute of Chemistry, University of Campinas, P.O. Box 6154, 13084-971 Campinas, SP (Brazil)

2011-11-07

Highlights: {yields} Near-Infrared Chemical Imaging was used for pellets analysis. {yields} Distribution of the components throughout the coatings layers and core of the pellets was estimated. {yields} Classical Least Squares (CLS) was used for calculation of the concentration maps. - Abstract: Pharmaceutical pellets are spherical or nearly spherical multi-unit dosage forms designed to optimize pharmacokinetics and pharmacodynamics features of drug release. The distribution of the pharmaceutical ingredients in the layers and core is a very important parameter for appropriate drug release, especially for pellets manufactured by the process of layer gain. Physical aspects of the sample are normally evaluated by Scanning Electron Microscopy (SEM), but it is in many cases unsuitable to provide conclusive chemical information about the distribution of the pharmaceutical ingredients in both layers and core. On the other hand, methods based on spectroscopic imaging can be very promising for this purpose. In this work, a Near-Infrared Chemical Imaging (NIR-CI) method was developed and applied to the analysis of diclophenac sodium pellets. Since all the compounds present in the sample were known in advance, Classical Least Squares (CLS) was used for calculations. The results have shown that the method was capable of providing chemical information about the distribution of the active ingredient and excipients in the core and coating layers and therefore can be complementary to SEM for the pharmaceutical development of pellets.

Vitiligo, drug induced (image)

Science.gov (United States)

... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

Imaging of mass distribution in paper by electrography technique, (3)

International Nuclear Information System (INIS)

Tomimasu, Hiroshi; Baba, Susumu; Luner, P.

1991-01-01

Characteristics of photographic films and a TV monitor system as electron beam detectors were studied. A photographic film with thin emulsion layer showed a peak in the basis weight calibration curve because of its limited absorption of electron energy. On the other hand, a photographic film with thick emulsion layer showed no peak and provided wide measurable basis weight range. However, films with thick emulsion layer were found unsuitable for practical use since it requires very long development time. Real-time mass distribution image of a paper sample were obtained with a TV monitor system for transmission electron microscope combined with an image analyzer. The system can image the sample of 11x9 mm with spatial resolution of 20 μm at different electron accelerating voltages. The TV monitor system gave no peak in the basis weight calibration curve and provided wide measurable basis weight range. (author)

Distant Determination of Bilirubin Distribution in Skin by Multi-Spectral Imaging

Science.gov (United States)

Saknite, I.; Jakovels, D.; Spigulis, J.

2011-01-01

For mapping the bilirubin distribution in bruised skin the multi-spectral imaging technique was employed, which made it possible to observe temporal changes of the bilirubin content in skin photo-types II and III. The obtained results confirm the clinical potential of this technique for skin bilirubin diagnostics.

Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

Science.gov (United States)

Berezhkovskiy, Leonid M

2013-02-01

The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter. Copyright © 2012 Wiley Periodicals, Inc.

Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

International Nuclear Information System (INIS)

Booij, Jan; Kemp, Paul

2008-01-01

[ 123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([ 123 I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [ 123 I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient's care and taking into account the pros and cons of doing so. (orig.)

Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

Science.gov (United States)

Yuan, Youyong; Liu, Bin

2014-09-10

A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

Controllable synthesis of a novel magnetic core-shell nanoparticle for dual-modal imaging and pH-responsive drug delivery

Science.gov (United States)

Xu, Chen; Zhang, Cheng; Wang, Yingxi; Li, Liu; Li, Ling; Whittaker, Andrew K.

2017-12-01

In this study, novel magnetic core-shell nanoparticles Fe3O4@La-BTC/GO have been synthesized by the layer-by-layer self-assembly (LBL) method and further modified by attachment of amino-modified PEG chains. The nanoparticles were thoroughly characterized by x-ray diffraction, FTIR, scanning electron microscopy and transmission electron microscopy. The core-shell structure was shown to be controlled by the LBL method. The drug loading of doxorubicin (DOX) within the Fe3O4@La-BTC/GO-PEG nanoparticles with different numbers of deposited layers was investigated. It was found that DOX loading increased with increasing number of metal organic framework coating layers, indicating that the drug loading can be controlled through the controllable LBL method. Cytotoxicity assays indicated that the Fe3O4@La-BTC/GO-PEG nanoparticles were biocompatible. The DOX was released rapidly at pH 3.8 and pH 5.8, but at pH 7.4 the rate and extent of release was greatly attenuated. The nanoparticles therefore demonstrate an excellent pH-triggered drug release. In addition, the particles could be tracked by magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI). A clear dose-dependent contrast enhancement in T 2-weighted MR images and fluorescence images indicate the potential of these nanoparticles as dual-mode MRI/FOI contrast agents.

In vitro membrane binding and protein binding (IAM MB/PB technology to estimate in vivo distribution: applications in early drug discovery

Directory of Open Access Journals (Sweden)

Klara Livia Valko

2017-03-01

Full Text Available The drug discovery process can be accelerated by chromatographic profiling of the analogs to model in vivo distribution and the major non-specific binding. A balanced potency and chromatographically determined membrane and protein binding (IAM MB/PB data enable selecting drug discovery compounds for further analysis that have the highest probability to show the desired in vivo distribution behavior for efficacy and reduced chance for toxicity. Although the basic principles of the technology have already appeared in numerous publications, the lack of standardized procedures limited its widespread applications especially in academia and small drug discovery biotech companies. In this paper, the standardized procedures are described that has been trademarked as Regis IAM MB/PB Technology®. Comparison between the Drug Efficiency Index (DEI=pIC50-logVdu+2 and generally used Ligand Lipophilicity Efficiency (LLE has been made, demonstrating the advantage of measured IAM and HSA binding over calculated log P. The power of the proposed chromatographic technology is demonstrated using the data of marketed drugs.

Tomographic reconstruction of storm time RC ion distribution from ENA images on board multiple spacecraft

Science.gov (United States)

Ma, Shu-Ying; Yan, Wei-Nan; Xu, Liang

2015-11-01

A quantitative retrieval of 3-D distribution of energetic ions as energetic neutral atoms (ENA) sources is a challenging task. In this paper the voxel computerized tomography (CT) method is initially applied to reconstruct the 3-D distribution of energetic ions in the magnetospheric ring current (RC) region from ENA emission images on board multiple spacecraft. To weaken the influence of low-altitude emission (LAE) on the reconstruction, the LAE-associated ENA intensities are corrected by invoking the thick-target approximation. To overcome the divergence in iteration due to discordant instrument biases, a differential ENA voxel CT method is developed. The method is proved reliable and advantageous by numerical simulation for the case of constant bias independent of viewing angle. Then this method is implemented with ENA data measured by the Two Wide-angle Imaging Neutral-atom Spectrometers mission which performs stereoscopic ENA imaging. The 3-D spatial distributions and energy spectra of RC ion flux intensity are reconstructed for energies of 4-50 keV during the main phase of a major magnetic storm. The retrieved ion flux distributions seem to correspond to an asymmetric partial RC, located mainly around midnight favoring the postmidnight with L = 3.5-7.0 in the equatorial plane. The RC ion distributions with magnetic local time depend on energy, with major equatorial flux peak for lower energy located east of that for higher energy. In comparison with the ion energy spectra measured by Time History of Events and Macroscale Interactions during Substorms-D satellite flying in the RC region, the retrieved spectrum from remotely sensed ENA images are well matched with the in situ measurements.

Altered distribution of technetium-99m sodium pertechnetate associated with antimicrobial therapy

International Nuclear Information System (INIS)

Castronuovo, J.J.; Chervu, L.R.; Milstein, D.M.

1985-01-01

Three patients underwent brain scanning for evaluation of central nervous system disease and were simultaneously treated for infectious diseases unrelated to the central nervous process. All revealed intense vascular pooling on their brain images. The imaging studies had been performed following the administration of Tc-99m pertechnetate. None of the patients had prior nuclear medicine examinations to suggest the causal effect of stannous ion as a source of interference. All of the patients were on combination antimicrobial drugs: two on sulfamethoxazole and trimethoprim, and one on isoniazid and ethambutol. One patient revealed 75% Tc-99m red cell tagging. Another patient's repeat brain scan with Tc-99m DTPA revealed normal distribution. Our findings suggest that patients on antimicrobial combination drug regimens who require brain scans should be imaged routinely with agents other than Tc-99m

Impact of amyloid imaging on drug development in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Mathis, Chester A. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)], E-mail: mathisca@upmc.edu; Lopresti, Brian J. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Klunk, William E. [Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

2007-10-15

Imaging agents capable of assessing amyloid-beta (A{beta}) content in vivo in the brains of Alzheimer's disease (AD) subjects likely will be important as diagnostic agents to detect A{beta} plaques in the brain as well as to help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of anti-amyloid therapeutics currently under development and in clinical trials. Positron emission tomography (PET) imaging studies of amyloid deposition in human subjects with several A{beta} imaging agents are currently underway. We reported the first PET studies of the carbon 11-labeled thioflavin-T derivative Pittsburgh Compound B in 2004, and this work has subsequently been extended to include a variety of subject groups, including AD patients, mild cognitive impairment patients and healthy controls. The ability to quantify regional A{beta} plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of A{beta} plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials.

Measurement of leakage dose distribution from Crookes tube using imaging plate

International Nuclear Information System (INIS)

Fujibuchi, Toshioh; Obara, Satoshi; Inoue, Hajime; Kato, Hideyuki; Kobayashi, Ikuo; Hosoda, Masahiro

2011-01-01

Crookes tube is used on an educational site in the junior high school and the high school, etc. for the purpose to learn the character of cathode rays. When using the tube, X rays are generated, however, there is few example of confirming in which direction to scatter in detail. Understanding how the distribution of the leakage dose is important because of efficient exposure decrease. The distribution of X rays generated from Crookes tube was measured by arranging imaging plates in six surroundings to enclose Crookes tube. The electron collided with a metal target and X rays had extended backward. The dose was greatly different depending on the direction. When experimenting with Crookes tube, it is necessary to consider not only the dose but also distribution. (author)

The rates and time-delay distribution of multiply imaged supernovae behind lensing clusters

Science.gov (United States)

Li, Xue; Hjorth, Jens; Richard, Johan

2012-11-01

Time delays of gravitationally lensed sources can be used to constrain the mass model of a deflector and determine cosmological parameters. We here present an analysis of the time-delay distribution of multiply imaged sources behind 17 strong lensing galaxy clusters with well-calibrated mass models. We find that for time delays less than 1000 days, at z = 3.0, their logarithmic probability distribution functions are well represented by P(log Δt) = 5.3 × 10-4Δttilde beta/M2502tilde beta, with tilde beta = 0.77, where M250 is the projected cluster mass inside 250 kpc (in 1014M⊙), and tilde beta is the power-law slope of the distribution. The resultant probability distribution function enables us to estimate the time-delay distribution in a lensing cluster of known mass. For a cluster with M250 = 2 × 1014M⊙, the fraction of time delays less than 1000 days is approximately 3%. Taking Abell 1689 as an example, its dark halo and brightest galaxies, with central velocity dispersions σ>=500kms-1, mainly produce large time delays, while galaxy-scale mass clumps are responsible for generating smaller time delays. We estimate the probability of observing multiple images of a supernova in the known images of Abell 1689. A two-component model of estimating the supernova rate is applied in this work. For a magnitude threshold of mAB = 26.5, the yearly rate of Type Ia (core-collapse) supernovae with time delays less than 1000 days is 0.004±0.002 (0.029±0.001). If the magnitude threshold is lowered to mAB ~ 27.0, the rate of core-collapse supernovae suitable for time delay observation is 0.044±0.015 per year.

CMP reflection imaging via interferometry of distributed subsurface sources

Science.gov (United States)

Kim, D.; Brown, L. D.; Quiros, D. A.

2015-12-01

The theoretical foundations of recovering body wave energy via seismic interferometry are well established. However in practice, such recovery remains problematic. Here, synthetic seismograms computed for subsurface sources are used to evaluate the geometrical combinations of realistic ambient source and receiver distributions that result in useful recovery of virtual body waves. This study illustrates how surface receiver arrays that span a limited distribution suite of sources, can be processed to reproduce virtual shot gathers that result in CMP gathers which can be effectively stacked with traditional normal moveout corrections. To verify the feasibility of the approach in practice, seismic recordings of 50 aftershocks following the magnitude of 5.8 Virginia earthquake occurred in August, 2011 have been processed using seismic interferometry to produce seismic reflection images of the crustal structure above and beneath the aftershock cluster. Although monotonic noise proved to be problematic by significantly reducing the number of usable recordings, the edited dataset resulted in stacked seismic sections characterized by coherent reflections that resemble those seen on a nearby conventional reflection survey. In particular, "virtual" reflections at travel times of 3 to 4 seconds suggest reflector sat approximately 7 to 12 km depth that would seem to correspond to imbricate thrust structures formed during the Appalachian orogeny. The approach described here represents a promising new means of body wave imaging of 3D structure that can be applied to a wide array of geologic and energy problems. Unlike other imaging techniques using natural sources, this technique does not require precise source locations or times. It can thus exploit aftershocks too small for conventional analyses. This method can be applied to any type of microseismic cloud, whether tectonic, volcanic or man-made.

Genetic diversity of Plasmodium falciparum and distribution of drug resistance haplotypes in Yemen.

Science.gov (United States)

Al-Hamidhi, Salama; Mahdy, Mohammed A K; Al-Hashami, Zainab; Al-Farsi, Hissa; Al-mekhlafi, Abdulsalam M; Idris, Mohamed A; Beja-Pereira, Albano; Babiker, Hamza A

2013-07-15

Despite evident success of malaria control in many sites in the Arabian Peninsula, malaria remains endemic in a few spots, in Yemen and south-west of Saudi Arabia. In addition to local transmission, imported malaria sustains an extra source of parasites that can challenge the strengths of local control strategies. This study examined the genetic diversity of Plasmodium falciparum in Yemen and mutations of drug resistant genes, to elucidate parasite structure and distribution of drug resistance genotypes in the region. Five polymorphic loci (MSP-2, Pfg377 and three microsatellites on chromosome 8) not involved in anti-malarial drug resistance, and four drug resistant genes (pfcrt, pfmdr1, dhfr and dhps) were genotyped in 108 P. falciparum isolates collected in three sites in Yemen: Dhamar, Hodeidah and Taiz. High diversity was seen in non-drug genes, pfg377 (He = 0.66), msp-2 (He = 0.80) and three microsatellites on chr 8, 7.7 kb (He = 0.88), 4.3 kb (He = 0.77) and 0.8 kb (He = 0.71). There was a high level of mixed-genotype infections (57%), with an average 1.8 genotypes per patient. No linkage disequilibrium was seen between drug resistant genes and the non-drug markers (p Yemen is indicative of a large parasite reservoir, which represents a challenge to control efforts. The presence of two distinct pfcrt genotype, CVIET and SVMNT, suggests that chloroquine resistance can possibly be related to a migratory path from Africa and Asia. The absence of the triple mutant dhfr genotype (IRN) and dhps mutations supports the use of artesunate + sulphadoxine-pyrimethamine as first-line therapy. However, the prevalent pfmdr1 genotype NFSND [21%] has previously been associated with tolerance/resistance response to artemisinin combination therapy (ACT). Regular surveys are, therefore, important to monitor spread of pfmdr1 and dhfr mutations and response to ACT.

Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning

Directory of Open Access Journals (Sweden)

Xiao-Yan Li

2013-10-01

Full Text Available The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7 have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC and X-ray diffraction (XRD results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system.

Differentiating gold nanorod samples using particle size and shape distributions from transmission electron microscope images

Science.gov (United States)

Grulke, Eric A.; Wu, Xiaochun; Ji, Yinglu; Buhr, Egbert; Yamamoto, Kazuhiro; Song, Nam Woong; Stefaniak, Aleksandr B.; Schwegler-Berry, Diane; Burchett, Woodrow W.; Lambert, Joshua; Stromberg, Arnold J.

2018-04-01

Size and shape distributions of gold nanorod samples are critical to their physico-chemical properties, especially their longitudinal surface plasmon resonance. This interlaboratory comparison study developed methods for measuring and evaluating size and shape distributions for gold nanorod samples using transmission electron microscopy (TEM) images. The objective was to determine whether two different samples, which had different performance attributes in their application, were different with respect to their size and/or shape descriptor distributions. Touching particles in the captured images were identified using a ruggedness shape descriptor. Nanorods could be distinguished from nanocubes using an elongational shape descriptor. A non-parametric statistical test showed that cumulative distributions of an elongational shape descriptor, that is, the aspect ratio, were statistically different between the two samples for all laboratories. While the scale parameters of size and shape distributions were similar for both samples, the width parameters of size and shape distributions were statistically different. This protocol fulfills an important need for a standardized approach to measure gold nanorod size and shape distributions for applications in which quantitative measurements and comparisons are important. Furthermore, the validated protocol workflow can be automated, thus providing consistent and rapid measurements of nanorod size and shape distributions for researchers, regulatory agencies, and industry.

Using Raman spectroscopic imaging for non-destructive analysis of filler distribution in chalk filled polypropylene

DEFF Research Database (Denmark)

Boros, Evelin; Porse, Peter Bak; Nielsen, Inga

2016-01-01

A feasibility study on using Raman spectral imaging for visualization and analysis of filler distribution in chalk filled poly-propylene samples has been carried out. The spectral images were acquired using a Raman spectrometer with 785 nm light source.Eight injection-molded samples with concentr...

Drug membrane interaction and the importance for drug transport, distribution, accumulation, efficacy and resistance.

Science.gov (United States)

Seydel, J K; Coats, E A; Cordes, H P; Wiese, M

1994-10-01

Some aspects of drug membrane interaction and its influence on drug transport, accumulation, efficacy and resistance have been discussed. The interactions manifest themselves macroscopically in changes in the physical and thermodynamic properties of "pure membranes" or bilayers. As various amounts of foreign molecules enter the membrane, in particular the main gel to liquid crystalline phase transition can be dramatically changed. This may change permeability, cell-fusion, cell resistance and may also lead to changes in conformation of the embedded receptor proteins. Furthermore, specific interactions with lipids may lead to drug accumulation in membranes and thus to much larger concentrations at the active site than present in the surrounding water phase. The lipid environment may also lead to changes in the preferred conformation of drug molecules. These events are directly related to drug efficacy. The determination of essential molecular criteria for the interaction could be used to design new and more selective therapeutics. This excursion in some aspects of drug membrane interaction underlines the importance of lipids and their interaction with drug molecules for our understanding of drug action, but this is not really a new thought but has been formulated in 1884 by THUDICUM: "Phospholipids are the centre, life and chemical soul of all bioplasm whatsoever, that of plants as well as of animals".

Contribution of positron emission tomography for the study of response variability to opioid drugs

International Nuclear Information System (INIS)

Auvity, Sylvain

2017-01-01

There is a high variability between patients in the initial analgesic response to opioid drugs. The chronic use of opioids leads to tolerance and may induce dependence or addiction. Current Positron Emission Tomography (PET) imaging methods, focusing on the impact of opioids on neuronal and synaptic functions, have failed to elucidate the parameters that control this variability of therapeutic response. A wealth of preclinical studies has addressed the possibility for neuro-immune or neuro-pharmacokinetic parameters to control the response to opioid drugs. Dedicated tools are thus required to investigate their impact on the pharmacology of opioid drugs in vivo and test their implication for variability in therapeutic response. The aim of this PhD project was to develop or to evaluate original methods to study the neuro-immune and neuro-pharmacokinetic components of the variability of response to opioid drugs. Opioid drugs were shown to interact with the innate immune System in the central nervous System (CNS) and to modulate the activity of glial cells. Glial cell activity is often hypothesized to modulate the analgesic efficacy of opioids and account for the development of tolerance and dependence. PET imaging using TSPO (Translocator protein 18 kDa) radioligands such as "1"8F-DPA-714 is the most advanced approach to non-invasively study glial cell activation. In nonhuman primates, we showed that acute morphine exposure increased the brain distribution of "1"8F-DPA-714, suggesting glial cell activation. The extent of the increase was linked to the baseline brain distribution of "1"8F-DPA-714, suggesting the presence of priming parameters in controlling the neuro-immune response to morphine exposure. In healthy rats, we showed that morphine-induced tolerance and withdrawal did not detectably increase the brain distribution of "1"8F-DPA-714 as well as the expression of other bio-markers of glial/micro-glial activation. Dedicated methods were then proposed to

Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs

International Nuclear Information System (INIS)

Maeda, Noriyuki; Miyazawa, Souichiro; Shimizu, Kosuke; Asai, Tomohiro; Yonezawa, Sei; Oku, Naoto; Kitazawa, Sadaya; Namba, Yukihiro; Tsukada, Hideo

2006-01-01

We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2- 18 F]2-fluoro-2-deoxy- D -glucose ([2- 18 F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment. (author)

Digi-Clima Grid: image processing and distributed computing for recovering historical climate data

Directory of Open Access Journals (Sweden)

Sergio Nesmachnow

2015-12-01

Full Text Available This article describes the Digi-Clima Grid project, whose main goals are to design and implement semi-automatic techniques for digitalizing and recovering historical climate records applying parallel computing techniques over distributed computing infrastructures. The specific tool developed for image processing is described, and the implementation over grid and cloud infrastructures is reported. A experimental analysis over institutional and volunteer-based grid/cloud distributed systems demonstrate that the proposed approach is an efficient tool for recovering historical climate data. The parallel implementations allow to distribute the processing load, achieving accurate speedup values.

Accurate study of FosPeg® distribution in a mouse model using fluorescence imaging technique and fluorescence white monte carlo simulations

DEFF Research Database (Denmark)

Xie, Haiyan; Liu, Haichun; Svenmarker, Pontus

2010-01-01

Fluorescence imaging is used for quantitative in vivo assessment of drug concentration. Light attenuation in tissue is compensated for through Monte-Carlo simulations. The intrinsic fluorescence intensity, directly proportional to the drug concentration, could be obtained....

Assessment of veterinary drugs in plants using pharmacokinetic approaches: The absorption, distribution and elimination of tetracycline and sulfamethoxazole in ephemeral vegetables

Science.gov (United States)

Chen, Hui-Ru; Rairat, Tirawat; Loh, Shih-Hurng; Wu, Yu-Chieh; Vickroy, Thomas W.

2017-01-01

The present study was carried out to demonstrate novel use of pharmacokinetic approaches to characterize drug behaviors/movements in the vegetables with implications to food safety. The absorption, distribution, metabolism and most importantly, the elimination of tetracycline (TC) and sulfamethoxazole (SMX) in edible plants Brassica rapa chinensis and Ipomoea aquatica grown hydroponically were demonstrated and studied using non-compartmental pharmacokinetic analysis. The results revealed drug-dependent and vegetable-dependent pharmacokinetic differences and indicated that ephemeral vegetables could have high capacity accumulating antibiotics (up to 160 μg g-1 for TC and 38 μg g-1 for SMX) within hours. TC concentration in the root (Cmax) could reach 11 times higher than that in the cultivation fluid and 3–28 times higher than the petioles/stems. Based on the volume of distribution (Vss), SMX was 3–6 times more extensively distributed than TC. Both antibiotics showed evident, albeit slow elimination phase with elimination half-lives ranging from 22 to 88 hours. For the first time drug elimination through the roots of a plant was demonstrated, and by viewing the root as a central compartment and continuous infusion without a loading dose as drug administration mode, it is possible to pharmacokinetically monitor the movement of antibiotics and their fate in the vegetables with more detailed information not previously available. Phyto-pharmacokinetic could be a new area worth developing new models for the assessment of veterinary drugs in edible plants. PMID:28797073

Development of a real time imaging-based guidance system of magnetic nanoparticles for targeted drug delivery

International Nuclear Information System (INIS)

Zhang, Xingming; Le, Tuan-Anh; Yoon, Jungwon

2017-01-01

Targeted drug delivery using magnetic nanoparticles is an efficient technique as molecules can be directed toward specific tissues inside a human body. For the first time, we implemented a real-time imaging-based guidance system of nanoparticles using untethered electro-magnetic devices for simultaneous guiding and tracking. In this paper a low-amplitude-excitation-field magnetic particle imaging (MPI) is introduced. Based on this imaging technology, a hybrid system comprised of an electromagnetic actuator and MPI was used to navigate nanoparticles in a non-invasive way. The real-time low-amplitude-excitation-field MPI and electromagnetic actuator of this navigation system are achieved by applying a time-division multiplexing scheme to the coil topology. A one dimensional nanoparticle navigation system was built to demonstrate the feasibility of the proposed approach and it could achieve a 2 Hz navigation update rate with the field gradient of 3.5 T/m during the imaging mode and 8.75 T/m during the actuation mode. Particles with both 90 nm and 5 nm diameters could be successfully manipulated and monitored in a tube through the proposed system, which can significantly enhance targeting efficiency and allow precise analysis in a real drug delivery. - Highlights: • A real-time system comprised of an electromagnetic actuator and a low-amplitude-excitation-field MPI can navigate magnetic nanoparticles. • The imaging scheme is feasible to enlarge field of view size. • The proposed navigation system can be cost efficient, compact, and optimized for targeting of the nanoparticles.

Development of a real time imaging-based guidance system of magnetic nanoparticles for targeted drug delivery

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xingming [School of Naval Architecture and Ocean Engineering, Harbin Institute of Technology at Weihai, Weihai, Shandong (China); School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Le, Tuan-Anh [School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Yoon, Jungwon, E-mail: jwyoon@gnu.ac.kr [School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

2017-04-01

Targeted drug delivery using magnetic nanoparticles is an efficient technique as molecules can be directed toward specific tissues inside a human body. For the first time, we implemented a real-time imaging-based guidance system of nanoparticles using untethered electro-magnetic devices for simultaneous guiding and tracking. In this paper a low-amplitude-excitation-field magnetic particle imaging (MPI) is introduced. Based on this imaging technology, a hybrid system comprised of an electromagnetic actuator and MPI was used to navigate nanoparticles in a non-invasive way. The real-time low-amplitude-excitation-field MPI and electromagnetic actuator of this navigation system are achieved by applying a time-division multiplexing scheme to the coil topology. A one dimensional nanoparticle navigation system was built to demonstrate the feasibility of the proposed approach and it could achieve a 2 Hz navigation update rate with the field gradient of 3.5 T/m during the imaging mode and 8.75 T/m during the actuation mode. Particles with both 90 nm and 5 nm diameters could be successfully manipulated and monitored in a tube through the proposed system, which can significantly enhance targeting efficiency and allow precise analysis in a real drug delivery. - Highlights: • A real-time system comprised of an electromagnetic actuator and a low-amplitude-excitation-field MPI can navigate magnetic nanoparticles. • The imaging scheme is feasible to enlarge field of view size. • The proposed navigation system can be cost efficient, compact, and optimized for targeting of the nanoparticles.

High-resolution imaging using a wideband MIMO radar system with two distributed arrays.

Science.gov (United States)

Wang, Dang-wei; Ma, Xiao-yan; Chen, A-Lei; Su, Yi

2010-05-01

Imaging a fast maneuvering target has been an active research area in past decades. Usually, an array antenna with multiple elements is implemented to avoid the motion compensations involved in the inverse synthetic aperture radar (ISAR) imaging. Nevertheless, there is a price dilemma due to the high level of hardware complexity compared to complex algorithm implemented in the ISAR imaging system with only one antenna. In this paper, a wideband multiple-input multiple-output (MIMO) radar system with two distributed arrays is proposed to reduce the hardware complexity of the system. Furthermore, the system model, the equivalent array production method and the imaging procedure are presented. As compared with the classical real aperture radar (RAR) imaging system, there is a very important contribution in our method that the lower hardware complexity can be involved in the imaging system since many additive virtual array elements can be obtained. Numerical simulations are provided for testing our system and imaging method.

Nanoimprinted distributed feedback dye laser sensor for real-time imaging of small molecule diffusion

DEFF Research Database (Denmark)

Vannahme, Christoph; Dufva, Martin; Kristensen, Anders

2014-01-01

Label-free imaging is a promising tool for the study of biological processes such as cell adhesion and small molecule signaling processes. In order to image in two dimensions of space current solutions require motorized stages which results in low imaging frame rates. Here, a highly sensitive...... distributed feedback (DFB) dye laser sensor for real-time label-free imaging without any moving parts enabling a frame rate of 12 Hz is presented. The presence of molecules on the laser surface results in a wavelength shift which is used as sensor signal. The unique DFB laser structure comprises several areas...

Drug induced lung disease

International Nuclear Information System (INIS)

Schaefer-Prokop, Cornelia; Eisenhuber, Edith

2010-01-01

There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

Science.gov (United States)

Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

2010-03-01

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

International Nuclear Information System (INIS)

Anantachaisilp, Suranan; Smith, Siwaporn Meejoo; Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong; Pratontep, Sirapat; Puttipipatkhachorn, Satit

2010-01-01

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ( 1 H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1 H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1 H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

Overdose prevention for injection drug users: Lessons learned from naloxone training and distribution programs in New York City

Directory of Open Access Journals (Sweden)

Nandi Vijay

2007-01-01

Full Text Available Abstract Background Fatal heroin overdose is a significant cause of mortality for injection drug users (IDUs. Many of these deaths are preventable because opiate overdoses can be quickly and safely reversed through the injection of Naloxone [brand name Narcan], a prescription drug used to revive persons who have overdosed on heroin or other opioids. Currently, in several cities in the United States, drug users are being trained in naloxone administration and given naloxone for immediate and successful reversals of opiate overdoses. There has been very little formal description of the challenges faced in the development and implementation of large-scale IDU naloxone administration training and distribution programs and the lessons learned during this process. Methods During a one year period, over 1,000 participants were trained in SKOOP (Skills and Knowledge on Opiate Prevention and received a prescription for naloxone by a medical doctor on site at a syringe exchange program (SEP in New York City. Participants in SKOOP were over the age of 18, current participants of SEPs, and current or former drug users. We present details about program design and lessons learned during the development and implementation of SKOOP. Lessons learned described in the manuscript are collectively articulated by the evaluators and implementers of the project. Results There were six primary challenges and lessons learned in developing, implementing, and evaluating SKOOP. These include a political climate surrounding naloxone distribution; b extant prescription drug laws; c initial low levels of recruitment into the program; d development of participant appropriate training methodology; e challenges in the design of a suitable formal evaluation; and f evolution of program response to naloxone. Conclusion Other naloxone distribution programs may anticipate similar challenges to SKOOP and we identify mechanisms to address them. Strategies include being flexible in

Fourier and granulometry methods on 3D images of soil surfaces for evaluating soil aggregate size distribution

DEFF Research Database (Denmark)

Jensen, T.; Green, O.; Munkholm, Lars Juhl

2016-01-01

The goal of this research is to present and compare two methods for evaluating soil aggregate size distribution based on high resolution 3D images of the soil surface. The methods for analyzing the images are discrete Fourier transform and granulometry. The results of these methods correlate...... with a measured weight distribution of the soil aggregates. The results have shown that it is possible to distinguish between the cultivated and the uncultivated soil surface. A sensor system suitable for capturing in-situ high resolution 3D images of the soil surface is also described. This sensor system...

The distribution of radiolabelled drug in animals infected with cutaneous leishmaniasis: comparison of free and liposome-bound sodium stibogluconate

International Nuclear Information System (INIS)

New, R.R.C.; Chance, M.L.; Critchley, M.

1982-01-01

Sodium stibogluconate, labelled with antimony 125, was used to study the altered distribution of drugs, entrapped by positively and negatively charged liposomes, used to treat cutaneous leishmaniasis. (U.K.)

Visualization of velocity field and phase distribution in gas-liquid two-phase flow by NMR imaging

International Nuclear Information System (INIS)

Matsui, G.; Monji, H.; Obata, J.

2004-01-01

NMR imaging has been applied in the field of fluid mechanics, mainly single phase flow, to visualize the instantaneous flow velocity field. In the present study, NMR imaging was used to visualize simultaneously both the instantaneous phase structure and velocity field of gas-liquid two-phase flow. Two methods of NMR imaging were applied. One is useful to visualize both the one component of liquid velocity and the phase distribution. This method was applied to horizontal two-phase flow and a bubble rising in stagnant oil. It was successful in obtaining some pictures of velocity field and phase distribution on the cross section of the pipe. The other is used to visualize a two-dimensional velocity field. This method was applied to a bubble rising in a stagnant water. The velocity field was visualized after and before the passage of a bubble at the measuring cross section. Furthermore, the distribution of liquid velocity was obtained. (author)

IMPROVING ACCESS TO DRUGS

Directory of Open Access Journals (Sweden)

Max Joseph Herman

2012-11-01

Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

Imaged brine inclusions in young sea ice—Shape, distribution and formation timing

DEFF Research Database (Denmark)

Galley, R.J.; Else, B.G.T.; Geilfus, Nicolas-Xavier

2015-01-01

Liquid inclusions in sea ice are variable and dependent on the myriad of physical conditions of the atmosphere– sea ice environment in which the sea ice was grown, and whether or not melting processes affected the sea ice. In that light, there exist relatively few observations and resultant quant...... in the context of the environment in which it grew. Finally, we show that a vertical brine volume distribution profile can be calculated using MR image data, extend- ing the (non-imaging) nuclear magnetic resonance work of others in this vein....

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

Science.gov (United States)

Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

2018-05-17

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

Directory of Open Access Journals (Sweden)

Vera ePaefgen

2015-09-01

Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

Is it time for cardiac innervation imaging?

Energy Technology Data Exchange (ETDEWEB)

Knuuti, J. [Turku Univ., Turku (Finland) Turku PET Center; Sipola, P. [Kuopio Univ., Kuopio (Finland)

2005-03-01

The autonomic nervous system plays an important role in the regulation of cardiac function and the regional distribution of cardiac nerve terminals can be visualized using scintigraphic techniques. The most commonly used tracer is iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts is used as an index of tracer uptake, and regional distribution is also assessed from tomographic images. The rate of clearance of the tracer can also be measured and indicates the function of the adrenergic system. Innervation imaging has been applied in patients with susceptibility to arrythmias, coronary artery disease, hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity. Abnormal adrenergic innervation or function appear to exist in many pathophysiological conditions indicating that sympathetic neurons are very susceptible to damage. Abnormal findings in innervation imaging also appear to have significant prognostic value especially in patients with cardiomyopathy. Recently, it has also been shown that innervation imaging can monitor drug-induced changes in cardiac adrenergic activity. Although innervation imaging holds great promise for clinical use, the method has not received wider clinical acceptance. Larger randomized studies are required to confirm the value of innervation imaging in various specific indications.

UV-vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup.

Science.gov (United States)

Sun, Yu; Chapman, Alex; Larsen, Susan W; Jensen, Henrik; Petersen, Nickolaj J; Goodall, David M; Østergaard, Jesper

2018-06-05

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

apART: system for the acquisition, processing, archiving, and retrieval of digital images in an open, distributed imaging environment

Science.gov (United States)

Schneider, Uwe; Strack, Ruediger

1992-04-01

apART reflects the structure of an open, distributed environment. According to the general trend in the area of imaging, network-capable, general purpose workstations with capabilities of open system image communication and image input are used. Several heterogeneous components like CCD cameras, slide scanners, and image archives can be accessed. The system is driven by an object-oriented user interface where devices (image sources and destinations), operators (derived from a commercial image processing library), and images (of different data types) are managed and presented uniformly to the user. Browsing mechanisms are used to traverse devices, operators, and images. An audit trail mechanism is offered to record interactive operations on low-resolution image derivatives. These operations are processed off-line on the original image. Thus, the processing of extremely high-resolution raster images is possible, and the performance of resolution dependent operations is enhanced significantly during interaction. An object-oriented database system (APRIL), which can be browsed, is integrated into the system. Attribute retrieval is supported by the user interface. Other essential features of the system include: implementation on top of the X Window System (X11R4) and the OSF/Motif widget set; a SUN4 general purpose workstation, inclusive ethernet, magneto optical disc, etc., as the hardware platform for the user interface; complete graphical-interactive parametrization of all operators; support of different image interchange formats (GIF, TIFF, IIF, etc.); consideration of current IPI standard activities within ISO/IEC for further refinement and extensions.

Molecular imaging of drug-modulated protein-protein interactions in living subjects.

Science.gov (United States)

Paulmurugan, Ramasamy; Massoud, Tarik F; Huang, Jing; Gambhir, Sanjiv S

2004-03-15

Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

Vertical distribution of total carbon, nitrogen and phosphorus in sediments of Drug Spring Lake, Wudalianchi

Science.gov (United States)

Zeng, Ying; Yang, Chen

2018-02-01

The content of total organic carbon, total nitrogen and total phosphorus in sediments of Drug Spring Lake was detected and their vertical distribution characteristic was analysed. Results showed that there were significant changes to the content of total organic carbon, total nitrogen and total phosphorus in different depth of the columnar sediments. Their highest content both appeared in the interval of 10cm to 25cm corresponding to the period of 1980s to 1990s, when the tourism of Wudalianchi scenic area began to develop. It reflected the impact of human activities on the Drug Spring Lake. That means the regulation was still not enough, although a series of pollution control measures adopted by the government in recent years had initial success.

Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

International Nuclear Information System (INIS)

Shen Jie; Sun Minjie; Ping Qineng; Ying Zhi; Liu Wen

2010-01-01

The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

Energy Technology Data Exchange (ETDEWEB)

Shen Jie; Sun Minjie; Ping Qineng; Ying Zhi; Liu Wen, E-mail: Pingqn2004@yahoo.com.cn [School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing (China)

2010-01-15

The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

Distribution of root exudates and mucilage in the rhizosphere: combining 14C imaging with neutron radiography

Science.gov (United States)

Holz, Maire; Carminati, Andrea; Kuzyakov, Yakov

2015-04-01

Water and nutrients will be the major factors limiting food production in future. Plant roots employ various mechanisms to increase the access to limited soil resources. Low molecular weight organic substances released by roots into the rhizosphere increase nutrient availability by interactions with microorganisms, while mucilage improves water availability under low moisture conditions. Though composition and quality of these substances have intensively been investigated, studies on the spatial distribution and quantification of exudates in soil are scarce. Our aim was to quantify and visualize root exudates and mucilage distribution around growing roots using neutron radiography and 14C imaging depending on drought stress. Plants were grown in rhizotrons well suited for neutron radiography and 14C imaging. Plants were exposed to various soil water contents experiencing different levels of drought stress. The water content in the rhizosphere was imaged during several drying/wetting cycles by neutron radiography. The radiographs taken a few hours after irrigation showed a wet region around the root tips showing the allocation and distribution of mucilage. The increased water content in the rhizosphere of the young root segments was related to mucilage concentrations by parameterization described in Kroener et al. (2014). In parallel 14C imaging of root after 14CO2 labeling of shoots (Pausch and Kuzyakov 2011) showed distribution of rhizodeposits including mucilage. Three days after setting the water content, plants were labeled in 14CO2 atmosphere. Two days later 14C distribution in soil was imaged by placing a phosphor-imaging plate on the rhizobox. To quantify rhizodeposition, 14C activity on the image was related to the absolute 14C activity in the soil and root after destructive sampling. By comparing the amounts of mucilage (neutron radiography) with the amount of total root derived C (14C imaging), we were able to differentiate between mucilage and root

A simple optode based imaging technique to measure O2 distribution and dynamics in tap water biofilms

DEFF Research Database (Denmark)

Staal, Marc Jaap; Prest, E.; Vrouwenvelder, H.

2011-01-01

window. The method is based on sequential imaging of the O2 dependent luminescence intensity, which are subsequently normalized with luminescent intensity images recorded under anoxic conditions. We present 2-dimensional O2 distribution images at the base of a tap water biofilm measured with the new...... is depleted during incubation....

Drug distribution and stability in extemporaneous preparations of meloxicam and carprofen after dilution and suspension at two storage temperatures.

Science.gov (United States)

Hawkins, Michelle G; Karriker, Margo J; Wiebe, Valerie; Taylor, Ian T; Kass, Philip H

2006-09-15

To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days. Prospective study. Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively. Preparations were stored at approximately 4 degrees C (39.2 degrees F) or 22 degrees C (71.6 degrees F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated. In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained > or = 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 +/- 0.04 and 0.21 +/- 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22 degrees C for 28 days yielded bacterial growth. DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Bioluminescent system for dynamic imaging of cell and animal behavior

Energy Technology Data Exchange (ETDEWEB)

Hara-Miyauchi, Chikako [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198 (Japan); Department of Biophysics and Biochemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Tsuji, Osahiko [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Hanyu, Aki [Division of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo 135-8550 (Japan); Okada, Seiji [Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Yasuda, Akimasa [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Fukano, Takashi [Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198 (Japan); Akazawa, Chihiro [Department of Biophysics and Biochemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Nakamura, Masaya [Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Imamura, Takeshi [Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan); Core Research for Evolutional Science and Technology, The Japan Science and Technology Corporation, Tokyo 135-8550 (Japan); Matsuzaki, Yumi [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Okano, Hirotaka James, E-mail: hjokano@jikei.ac.jp [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Division of Regenerative Medicine Jikei University School of Medicine, Tokyo 150-8461 (Japan); and others

2012-03-09

Highlights: Black-Right-Pointing-Pointer We combined a yellow variant of GFP and firefly luciferase to make ffLuc-cp156. Black-Right-Pointing-Pointer ffLuc-cp156 showed improved photon yield in cultured cells and transgenic mice. Black-Right-Pointing-Pointer ffLuc-cp156 enabled video-rate bioluminescence imaging of freely-moving animals. Black-Right-Pointing-Pointer ffLuc-cp156 mice enabled tracking real-time drug delivery in conscious animals. -- Abstract: The current utility of bioluminescence imaging is constrained by a low photon yield that limits temporal sensitivity. Here, we describe an imaging method that uses a chemiluminescent/fluorescent protein, ffLuc-cp156, which consists of a yellow variant of Aequorea GFP and firefly luciferase. We report an improvement in photon yield by over three orders of magnitude over current bioluminescent systems. We imaged cellular movement at high resolution including neuronal growth cones and microglial cell protrusions. Transgenic ffLuc-cp156 mice enabled video-rate bioluminescence imaging of freely moving animals, which may provide a reliable assay for drug distribution in behaving animals for pre-clinical studies.

Bioluminescent system for dynamic imaging of cell and animal behavior

International Nuclear Information System (INIS)

Hara-Miyauchi, Chikako; Tsuji, Osahiko; Hanyu, Aki; Okada, Seiji; Yasuda, Akimasa; Fukano, Takashi; Akazawa, Chihiro; Nakamura, Masaya; Imamura, Takeshi; Matsuzaki, Yumi; Okano, Hirotaka James

2012-01-01

Highlights: ► We combined a yellow variant of GFP and firefly luciferase to make ffLuc-cp156. ► ffLuc-cp156 showed improved photon yield in cultured cells and transgenic mice. ► ffLuc-cp156 enabled video-rate bioluminescence imaging of freely-moving animals. ► ffLuc-cp156 mice enabled tracking real-time drug delivery in conscious animals. -- Abstract: The current utility of bioluminescence imaging is constrained by a low photon yield that limits temporal sensitivity. Here, we describe an imaging method that uses a chemiluminescent/fluorescent protein, ffLuc-cp156, which consists of a yellow variant of Aequorea GFP and firefly luciferase. We report an improvement in photon yield by over three orders of magnitude over current bioluminescent systems. We imaged cellular movement at high resolution including neuronal growth cones and microglial cell protrusions. Transgenic ffLuc-cp156 mice enabled video-rate bioluminescence imaging of freely moving animals, which may provide a reliable assay for drug distribution in behaving animals for pre-clinical studies.

Performance of Web-based image distribution: client-oriented measurements

International Nuclear Information System (INIS)

Bergh, B.; Pietsch, M.; Schlaefke, A.; Vogl, T.J.

2003-01-01

The aim of this study was to define a clinically suitable personal computer (PC) configuration for Web-based image distribution and to assess the influence of different hard- and software configurations on the performance. Through specially developed software the time-to-display (TTD) for various PC configurations was measured. Different processor speeds, random access memory (RAM), screen resolutions, graphic adapters, network speeds, operating systems and examination types (computed radiography, CT, MRI) were evaluated, providing more than half a million measurements. Processor speed was the most relevant factor for the TTD; doubling the speed halved the TTD. Under processor speeds of 350 MHz, TTD mostly remained above 5 s for 1 CR or 16 CT images. Here Windows NT with lossy compression were superior. Processor speeds of 350 MHz and over delivered TTD <5 s. In this case Windows 2000 and lossless compression were preferable. Screen resolutions above 1280 x 1024 pixels increased the TTD mainly for CR images. The RAM amount, network speed and graphic adapter did not have a significant influence. The minimum threshold for clinical routine is any standard off-the-shelf PC better than Pentium II 350 MHz, 128 MB RAM; hence, high-end PC hardware is not required. (orig.)

Imaging phase holdup distribution of three phase flow systems using dual source gamma ray tomography

International Nuclear Information System (INIS)

Varma, Rajneesh; Al-Dahhan, Muthanna; O'Sullivan, Joseph

2008-01-01

Full text: Multiphase reaction and process systems are used in abundance in the chemical and biochemical industry. Tomography has been successfully employed to visualize the hydrodynamics of multiphase systems. Most of the tomography methods (gamma ray, x-ray and electrical capacitance and resistance) have been successfully implemented for two phase dynamic systems. However, a significant number of chemical and biochemical systems consists of dynamic three phases. Research effort directed towards the development of tomography techniques to image such dynamic system has met with partial successes for specific systems with applicability to limited operating conditions. A dual source tomography scanner has been developed that uses the 661 keV and 1332 keV photo peaks from the 137 Cs and 60 Co for imaging three phase systems. A new approach has been developed and applied that uses the polyenergetic Alternating Minimization (A-M) algorithm, developed by O'Sullivan and Benac (2007), for imaging the holdup distribution in three phases' dynamic systems. The new approach avoids the traditional post image processing approach used to determine the holdup distribution where the attenuation images of the mixed flow obtained from gamma ray photons of two different energies are used to determine the holdup of three phases. In this approach the holdup images are directly reconstructed from the gamma ray transmission data. The dual source gamma ray tomography scanner and the algorithm were validated using a three phase phantom. Based in the validation, three phase holdup studies we carried out in slurry bubble column containing gas liquid and solid phases in a dynamic state using the dual energy gamma ray tomography. The key results of the holdup distribution studies in the slurry bubble column along with the validation of the dual source gamma ray tomography system would be presented and discussed

Synthesis and Properties of Star HPMA Copolymer Nanocarriers Synthesised by RAFT Polymerisation Designed for Selective Anticancer Drug Delivery and Imaging.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Janoušková, Olga; Kostka, Libor; Ulbrich, Karel; Etrych, Tomáš

2015-06-01

High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with Mw values ranging from 2 · 10(5) to 6 · 10(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products

Science.gov (United States)

Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA) and ivermectin (IVR)] were used to evaluate drug distribution between milk fat and skim milk fractions of cow milk. Greater than 90% of radioactivity...

A data grid for imaging-based clinical trials

Science.gov (United States)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

PCI bus content-addressable-memory (CAM) implementation on FPGA for pattern recognition/image retrieval in a distributed environment

Science.gov (United States)

Megherbi, Dalila B.; Yan, Yin; Tanmay, Parikh; Khoury, Jed; Woods, C. L.

2004-11-01

Recently surveillance and Automatic Target Recognition (ATR) applications are increasing as the cost of computing power needed to process the massive amount of information continues to fall. This computing power has been made possible partly by the latest advances in FPGAs and SOPCs. In particular, to design and implement state-of-the-Art electro-optical imaging systems to provide advanced surveillance capabilities, there is a need to integrate several technologies (e.g. telescope, precise optics, cameras, image/compute vision algorithms, which can be geographically distributed or sharing distributed resources) into a programmable system and DSP systems. Additionally, pattern recognition techniques and fast information retrieval, are often important components of intelligent systems. The aim of this work is using embedded FPGA as a fast, configurable and synthesizable search engine in fast image pattern recognition/retrieval in a distributed hardware/software co-design environment. In particular, we propose and show a low cost Content Addressable Memory (CAM)-based distributed embedded FPGA hardware architecture solution with real time recognition capabilities and computing for pattern look-up, pattern recognition, and image retrieval. We show how the distributed CAM-based architecture offers a performance advantage of an order-of-magnitude over RAM-based architecture (Random Access Memory) search for implementing high speed pattern recognition for image retrieval. The methods of designing, implementing, and analyzing the proposed CAM based embedded architecture are described here. Other SOPC solutions/design issues are covered. Finally, experimental results, hardware verification, and performance evaluations using both the Xilinx Virtex-II and the Altera Apex20k are provided to show the potential and power of the proposed method for low cost reconfigurable fast image pattern recognition/retrieval at the hardware/software co-design level.

Antibiotic distribution channels in Thailand: results of key-informant interviews, reviews of drug regulations and database searches.

Science.gov (United States)

Sommanustweechai, Angkana; Chanvatik, Sunicha; Sermsinsiri, Varavoot; Sivilaikul, Somsajee; Patcharanarumol, Walaiporn; Yeung, Shunmay; Tangcharoensathien, Viroj

2018-02-01

To analyse how antibiotics are imported, manufactured, distributed and regulated in Thailand. We gathered information, on antibiotic distribution in Thailand, in in-depth interviews - with 43 key informants from farms, health facilities, pharmaceutical and animal feed industries, private pharmacies and regulators- and in database and literature searches. In 2016-2017, licensed antibiotic distribution in Thailand involves over 700 importers and about 24 000 distributors - e.g. retail pharmacies and wholesalers. Thailand imports antibiotics and active pharmaceutical ingredients. There is no system for monitoring the distribution of active ingredients, some of which are used directly on farms, without being processed. Most antibiotics can be bought from pharmacies, for home or farm use, without a prescription. Although the 1987 Drug Act classified most antibiotics as "dangerous drugs", it only classified a few of them as prescription-only medicines and placed no restrictions on the quantities of antibiotics that could be sold to any individual. Pharmacists working in pharmacies are covered by some of the Act's regulations, but the quality of their dispensing and prescribing appears to be largely reliant on their competences. In Thailand, most antibiotics are easily and widely available from retail pharmacies, without a prescription. If the inappropriate use of active pharmaceutical ingredients and antibiotics is to be reduced, we need to reclassify and restrict access to certain antibiotics and to develop systems to audit the dispensing of antibiotics in the retail sector and track the movements of active ingredients.

Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

Energy Technology Data Exchange (ETDEWEB)

Lv, Ouyang; Tao, Yongxin; Qin, Yong [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China); Chen, Chuanxiang [School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003 (China); Pan, Yan; Deng, Linhong [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Liu, Li [School of pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164 (China); Kong, Yong, E-mail: yzkongyong@126.com [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China)

2016-10-01

Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH{sub 2} groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH{sub 2} on CS result in a pH-dependent drug delivery.

Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

International Nuclear Information System (INIS)

Lv, Ouyang; Tao, Yongxin; Qin, Yong; Chen, Chuanxiang; Pan, Yan; Deng, Linhong; Liu, Li; Kong, Yong

2016-01-01

Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH_2 groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH_2 on CS result in a pH-dependent drug delivery.

Human brain imaging

International Nuclear Information System (INIS)

Kuhar, M.J.

1987-01-01

Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

Iterative inversion of global magnetospheric ion distributions using energetic neutral atom (ENA images recorded by the NUADU/TC2 instrument

Directory of Open Access Journals (Sweden)

L. Lu

2008-06-01

Full Text Available A method has been developed for extracting magnetospheric ion distributions from Energetic Neutral Atom (ENA measurements made by the NUADU instrument on the TC-2 spacecraft. Based on a constrained linear inversion, this iterative technique is suitable for use in the case of an ENA image measurement, featuring a sharply peaked spatial distribution. The method allows for magnetospheric ion distributions to be extracted from a low-count ENA image recorded over a short integration time (5 min. The technique is demonstrated through its application to a set of representative ENA images recorded in energy Channel~2 (hydrogen: 50–81 keV, oxygen: 138–185 keV of the NUADU instrument during a geomagnetic storm. It is demonstrated that this inversion method provides a useful tool for extracting ion distribution information from ENA data that are characterized by high temporal and spatial resolution. The recovered ENA images obtained from inverted ion fluxes match most effectively the measurements made at maximum ENA intensity.

Extraction of density distributions and particle locations from hologram images

Energy Technology Data Exchange (ETDEWEB)

Okamoto, Koji; Ikeda, Koh; Madarame, Haruki [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab.

1996-10-01

In this study, the simultaneous measurement technique for three-dimensional density and three-dimensional velocity distributions was evaluated. The Holographic Particle Image Velocimetry (HPIV) was the technique to record the three-dimensional position of the tracer particle on the hologram. When there were density distributions in the interrogation region, the plane optical wave may be modulated because of the difference of the refraction indices. Then, both of the plane wave modulated by density and the spherical wave by particle scatter were interfered with the reference beam, being recorded on the hologram. With reconstructing the hologram, the both of the modulated plane wave and spherical wave were reconstructed. Since the plane wave and spherical wave had low and high frequency, respectively, the two information could be separated using low-pass and high-pass filter. In the experiment, a jet of carbon-dioxide into air with mist were measured. Both mist particle position and the fringe shift caused by the density distribution were well observed, showing the effectiveness of the proposed technique. (author)

Combination of panoramic and fluorescence endoscopic images to obtain tumor spatial distribution information useful for bladder cancer detection

Science.gov (United States)

Olijnyk, S.; Hernández Mier, Y.; Blondel, W. C. P. M.; Daul, C.; Wolf, D.; Bourg-Heckly, G.

2007-07-01

Bladder cancer is widely spread. Moreover, carcinoma in situ can be difficult to diagnose as it may be difficult to see, and become invasive in 50 % of case. Non invasive diagnosis methods like photodynamic or autofluorescence endoscopy allow enhancing sensitivity and specificity. Besides, bladder tumors can be multifocal. Multifocality increases the probability of recurrence and infiltration into bladder muscle. Analysis of spatial distribution of tumors could be used to improve diagnosis. We explore the feasibility to combine fluorescence and spatial information on phantoms. We developed a system allowing the acquisition of consecutive images under white light or UV excitation alternatively and automatically along the video sequence. We also developed an automatic image processing algorithm to build a partial panoramic image from a cystoscopic sequence of images. Fluorescence information is extracted from wavelength bandpass filtered images and superimposed over the cartography. Then, spatial distribution measures of fluorescent spots can be computed. This cartography can be positioned on a 3D generic shape of bladder by selecting some reference points. Our first results on phantoms show that it is possible to obtain cartography with fluorescent spots and extract quantitative information of their spatial distribution on a "wide" field of view basis.

Photon event distribution sampling: an image formation technique for scanning microscopes that permits tracking of sub-diffraction particles with high spatial and temporal resolutions.

Science.gov (United States)

Larkin, J D; Publicover, N G; Sutko, J L

2011-01-01

In photon event distribution sampling, an image formation technique for scanning microscopes, the maximum likelihood position of origin of each detected photon is acquired as a data set rather than binning photons in pixels. Subsequently, an intensity-related probability density function describing the uncertainty associated with the photon position measurement is applied to each position and individual photon intensity distributions are summed to form an image. Compared to pixel-based images, photon event distribution sampling images exhibit increased signal-to-noise and comparable spatial resolution. Photon event distribution sampling is superior to pixel-based image formation in recognizing the presence of structured (non-random) photon distributions at low photon counts and permits use of non-raster scanning patterns. A photon event distribution sampling based method for localizing single particles derived from a multi-variate normal distribution is more precise than statistical (Gaussian) fitting to pixel-based images. Using the multi-variate normal distribution method, non-raster scanning and a typical confocal microscope, localizations with 8 nm precision were achieved at 10 ms sampling rates with acquisition of ~200 photons per frame. Single nanometre precision was obtained with a greater number of photons per frame. In summary, photon event distribution sampling provides an efficient way to form images when low numbers of photons are involved and permits particle tracking with confocal point-scanning microscopes with nanometre precision deep within specimens. © 2010 The Authors Journal of Microscopy © 2010 The Royal Microscopical Society.

Dopamine transporter imaging with [{sup 123}I]FP-CIT SPECT: potential effects of drugs

Energy Technology Data Exchange (ETDEWEB)

Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Kemp, Paul [Southampton University Hospitals Trust, Department of Nuclear Medicine, Southampton (United Kingdom)

2008-02-15

[{sup 123}I]N-{omega}-fluoropropyl-2{beta}-carbomethoxy-3{beta}-{l_brace}4-iodophenyl{r_brace}nortropane ([{sup 123}I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [{sup 123}I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient's care and taking into account the pros and cons of doing so. (orig.)

Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells

Directory of Open Access Journals (Sweden)

Junji Itou

2015-12-01

Full Text Available Three-dimensional (3D cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture. We used a pulse-labeling technique with a photoconvertible fluorescent protein Kaede to identify non-proliferated cells. This assay allows us to observe change in cell proliferation in 3D culture by simple imaging. Using this assay, we obtained the data of the effects of anti-cancer drugs, 5-fluorouracil and PD0332991 in a breast cancer cell line, MCF-7.

Synthesis and In Vitro Characterization of Fe3+-Doped Layered Double Hydroxide Nanorings as a Potential Imageable Drug Delivery System

Directory of Open Access Journals (Sweden)

Lijun Wang

2017-09-01

Full Text Available Highly dispersed Fe3+-doped layered double hydroxide (LDH-Fe nanorings were obtained by a simple coprecipitation-acid etching approach. The morphology, structure, magnetic resonance imaging (MRI performance in vitro, drug loading and releasing, Fe3+ leakage, and cytotoxicity of the as-prepared LDH-Fe nanorings were characterized. The LDH-Fe nanorings showed good water dispersity and a well-crystallized structure. The DLS average size of nanoparticles was measured to be 94.5 nm. Moreover, the MRI tests showed a favourable T1-weighted MRI performance of the LDH-Fe nanoring with r1 values of 0.54 and 1.68, and low r2/r1 ratios of 10.1 and 6.3, pre- and after calcination, respectively. The nanoparticles also showed high model drug (ibuprofen loading capacities, low Fe3+ leakage, and negligible cytotoxicity. All these results demonstrate the potential of LDH-Fe nanorings as an imageable drug delivery system.

Extraction of density distributions and particle locations from hologram images

International Nuclear Information System (INIS)

Ikeda, Koh; Okamoto, Koji; Kato, Fumitake; Shimizu, Isao.

1996-01-01

In this study, the simultaneous measurement technique for three-dimensional density and three-dimensional velocity distributions was evaluated. The Holographic Particle Image Velocimetry (HPIV) was the technique to record the three-dimensional position of the tracer particle on the hologram. In the hologram, the interferogram between reference beam and particle scattering were recorded. When there were density distributions in the interrogation region, the plane optical wave may be modulated because of the difference of the refraction indices. Then, both of the plane wave modulated by density and the spherical wave by particle scatter were interfered with the reference beam, being recorded on the hologram. With reconstructing the hologram, the both of the modulated plane wave and spherical wave were reconstructed. Since the plane wave and spherical wave had low and high frequency, respectively, the plane wave was reconstructed with the low-pass filter, resulting in the information of the density distributions to be obtained. With the high-pass filter, the particle three-dimensional positions was determined, i.e., the same procedure with the original HPIV technique. In the experiment, a jet of carbon-dioxide into air with mist were measured. Both mist particle position and the fringe shift caused by the density distribution were well observed, showing the effectiveness of the proposed technique. (author)

Modeling of Potential Distribution of Electrical Capacitance Tomography Sensor for Multiphase Flow Image

Directory of Open Access Journals (Sweden)

S. Sathiyamoorthy

2007-09-01

Full Text Available Electrical Capacitance Tomography (ECT was used to develop image of various multi phase flow of gas-liquid-solid in a closed pipe. The principal difficulties to obtained real time image from ECT sensor are permittivity distribution across the plate and capacitance is nonlinear; the electric field is distorted by the material present and is also sensitive to measurement errors and noise. This work present a detailed description is given on method employed for image reconstruction from the capacitance measurements. The discretization and iterative algorithm is developed for improving the predictions with minimum error. The author analyzed eight electrodes square sensor ECT system with two-phase water-gas and solid-gas.

Electrochemical Impedance Imaging via the Distribution of Diffusion Times

Science.gov (United States)

Song, Juhyun; Bazant, Martin Z.

2018-03-01

We develop a mathematical framework to analyze electrochemical impedance spectra in terms of a distribution of diffusion times (DDT) for a parallel array of random finite-length Warburg (diffusion) or Gerischer (reaction-diffusion) circuit elements. A robust DDT inversion method is presented based on complex nonlinear least squares regression with Tikhonov regularization and illustrated for three cases of nanostructured electrodes for energy conversion: (i) a carbon nanotube supercapacitor, (ii) a silicon nanowire Li-ion battery, and (iii) a porous-carbon vanadium flow battery. The results demonstrate the feasibility of nondestructive "impedance imaging" to infer microstructural statistics of random, heterogeneous materials.

Image quality of microcalcifications in digital breast tomosynthesis: Effects of projection-view distributions

OpenAIRE

Lu, Yao; Chan, Heang-Ping; Wei, Jun; Goodsitt, Mitch; Carson, Paul L.; Hadjiiski, Lubomir; Schmitz, Andrea; Eberhard, Jeffrey W.; Claus, Bernhard E. H.

2011-01-01

Purpose: To analyze the effects of projection-view (PV) distribution on the contrast and spatial blurring of microcalcifications on the tomosynthesized slices (X-Y plane) and along the depth (Z) direction for the same radiation dose in digital breast tomosynthesis (DBT).Methods: A GE GEN2 prototype DBT system was used for acquisition of DBT scans. The system acquires PV images from 21 angles in 3° increments over a ±30° range. From these acquired PV images, the authors selected six subsets of...

Ship Detection in Gaofen-3 SAR Images Based on Sea Clutter Distribution Analysis and Deep Convolutional Neural Network.

Science.gov (United States)

An, Quanzhi; Pan, Zongxu; You, Hongjian

2018-01-24

Target detection is one of the important applications in the field of remote sensing. The Gaofen-3 (GF-3) Synthetic Aperture Radar (SAR) satellite launched by China is a powerful tool for maritime monitoring. This work aims at detecting ships in GF-3 SAR images using a new land masking strategy, the appropriate model for sea clutter and a neural network as the discrimination scheme. Firstly, the fully convolutional network (FCN) is applied to separate the sea from the land. Then, by analyzing the sea clutter distribution in GF-3 SAR images, we choose the probability distribution model of Constant False Alarm Rate (CFAR) detector from K-distribution, Gamma distribution and Rayleigh distribution based on a tradeoff between the sea clutter modeling accuracy and the computational complexity. Furthermore, in order to better implement CFAR detection, we also use truncated statistic (TS) as a preprocessing scheme and iterative censoring scheme (ICS) for boosting the performance of detector. Finally, we employ a neural network to re-examine the results as the discrimination stage. Experiment results on three GF-3 SAR images verify the effectiveness and efficiency of this approach.

The Washington Needle Depot: fitting healthcare to injection drug users rather than injection drug users to healthcare: moving from a syringe exchange to syringe distribution model

Directory of Open Access Journals (Sweden)

Glickman Andrea

2010-01-01

Full Text Available Abstract Needle exchange programs chase political as well as epidemiological dragons, carrying within them both implicit moral and political goals. In the exchange model of syringe distribution, injection drug users (IDUs must provide used needles in order to receive new needles. Distribution and retrieval are co-existent in the exchange model. Likewise, limitations on how many needles can be received at a time compel addicts to have multiple points of contact with professionals where the virtues of treatment and detox are impressed upon them. The centre of gravity for syringe distribution programs needs to shift from needle exchange to needle distribution, which provides unlimited access to syringes. This paper provides a case study of the Washington Needle Depot, a program operating under the syringe distribution model, showing that the distribution and retrieval of syringes can be separated with effective results. Further, the experience of IDUs is utilized, through paid employment, to provide a vulnerable population of people with clean syringes to prevent HIV and HCV.

[Imaging Mass Spectrometry in Histopathologic Analysis].

Science.gov (United States)

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

Energy Technology Data Exchange (ETDEWEB)

Anantachaisilp, Suranan; Smith, Siwaporn Meejoo [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong [National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Pratontep, Sirapat [College of KMITL Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Bangkok (Thailand); Puttipipatkhachorn, Satit, E-mail: uracha@nanotec.or.th [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand)

2010-03-26

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of {gamma}-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the {gamma}-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ({sup 1}H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the {sup 1}H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of {gamma}-oryzanol inside the lipid nanoparticles, the {sup 1}H-NMR revealed that the chemical shifts of the liquid lipid in {gamma}-oryzanol loaded systems were found at rather higher field than those in {gamma}-oryzanol free systems, suggesting incorporation of {gamma}-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of {gamma}-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models

A novel method for the investigation of liquid/liquid distribution coefficients and interface permeabilities applied to the water-octanol-drug system.

Science.gov (United States)

Stein, Paul C; di Cagno, Massimiliano; Bauer-Brandl, Annette

2011-09-01

In this work a new, accurate and convenient technique for the measurement of distribution coefficients and membrane permeabilities based on nuclear magnetic resonance (NMR) is described. This method is a novel implementation of localized NMR spectroscopy and enables the simultaneous analysis of the drug content in the octanol and in the water phase without separation. For validation of the method, the distribution coefficients at pH = 7.4 of four active pharmaceutical ingredients (APIs), namely ibuprofen, ketoprofen, nadolol, and paracetamol (acetaminophen), were determined using a classical approach. These results were compared to the NMR experiments which are described in this work. For all substances, the respective distribution coefficients found with the two techniques coincided very well. Furthermore, the NMR experiments make it possible to follow the distribution of the drug between the phases as a function of position and time. Our results show that the technique, which is available on any modern NMR spectrometer, is well suited to the measurement of distribution coefficients. The experiments present also new insight into the dynamics of the water-octanol interface itself and permit measurement of the interface permeability.

"Cyt/Nuc," a Customizable and Documenting ImageJ Macro for Evaluation of Protein Distributions Between Cytosol and Nucleus.

Science.gov (United States)

Grune, Tilman; Kehm, Richard; Höhn, Annika; Jung, Tobias

2018-05-01

Large amounts of data from multi-channel, high resolution, fluorescence microscopic images require tools that provide easy, customizable, and reproducible high-throughput analysis. The freeware "ImageJ" has become one of the standard tools for scientific image analysis. Since ImageJ offers recording of "macros," even a complex multi-step process can be easily applied fully automated to large numbers of images, saving both time and reducing human subjective evaluation. In this work, we present "Cyt/Nuc," an ImageJ macro, able to recognize and to compare the nuclear and cytosolic areas of tissue samples, in order to investigate distributions of immunostained proteins between both compartments, while it documents in detail the whole process of evaluation and pattern recognition. As practical example, the redistribution of the 20S proteasome, the main intracellular protease in mammalian cells, is investigated in NZO-mouse liver after feeding the animals different diets. A significant shift in proteasomal distribution between cytosol and nucleus in response to metabolic stress was revealed using "Cyt/Nuc" via automatized quantification of thousands of nuclei within minutes. "Cyt/Nuc" is easy to use and highly customizable, matches the precision of careful manual evaluation and bears the potential for quick detection of any shift in intracellular protein distribution. © 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

41 CFR 102-41.230 - May SASPs pick up or store donated drug paraphernalia in their distribution centers?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false May SASPs pick up or store donated drug paraphernalia in their distribution centers? 102-41.230 Section 102-41.230 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of bang polymer gel dosimeters

International Nuclear Information System (INIS)

Ibbott, Geoffrey S.; Maryanski, Marek J.; Eastman, Peter; Holcomb, Stephen D.; Yashan, Zhang; Avison, Robin G.; Sanders, Michael; Gore, John C.

1997-01-01

Purpose/Objective: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, non coplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers. Methods and Materials: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses the Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N'-methylene-bis acrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90 deg. -τ-180 deg. -τ-acquire, for different values of τ). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential

Hidden Wholesale: The drug diffusing capacity of online drug cryptomarkets

OpenAIRE

Aldridge, Judith A; Décary-Hétu, David

2016-01-01

Background: In spite of globalizing processes ‘offline’ retail drug markets remain localized and – in recent decades – typically ‘closed’, in which dealers sell primarily to known customers. We characterize drug cryptomarkets as ‘anonymous open’ marketplaces that allow the diffusion of drugs across locales. Where cryptomarket customers make stock-sourcing purchases for offline distribution, the cryptomarket may indirectly serve drug users who are not themselves cryptomarket customers, thereby...

Conditional probability distribution associated to the E-M image reconstruction algorithm for neutron stimulated emission tomography

International Nuclear Information System (INIS)

Viana, R.S.; Yoriyaz, H.; Santos, A.

2011-01-01

The Expectation-Maximization (E-M) algorithm is an iterative computational method for maximum likelihood (M-L) estimates, useful in a variety of incomplete-data problems. Due to its stochastic nature, one of the most relevant applications of E-M algorithm is the reconstruction of emission tomography images. In this paper, the statistical formulation of the E-M algorithm was applied to the in vivo spectrographic imaging of stable isotopes called Neutron Stimulated Emission Computed Tomography (NSECT). In the process of E-M algorithm iteration, the conditional probability distribution plays a very important role to achieve high quality image. This present work proposes an alternative methodology for the generation of the conditional probability distribution associated to the E-M reconstruction algorithm, using the Monte Carlo code MCNP5 and with the application of the reciprocity theorem. (author)

Conditional probability distribution associated to the E-M image reconstruction algorithm for neutron stimulated emission tomography

Energy Technology Data Exchange (ETDEWEB)

Viana, R.S.; Yoriyaz, H.; Santos, A., E-mail: rodrigossviana@gmail.com, E-mail: hyoriyaz@ipen.br, E-mail: asantos@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

The Expectation-Maximization (E-M) algorithm is an iterative computational method for maximum likelihood (M-L) estimates, useful in a variety of incomplete-data problems. Due to its stochastic nature, one of the most relevant applications of E-M algorithm is the reconstruction of emission tomography images. In this paper, the statistical formulation of the E-M algorithm was applied to the in vivo spectrographic imaging of stable isotopes called Neutron Stimulated Emission Computed Tomography (NSECT). In the process of E-M algorithm iteration, the conditional probability distribution plays a very important role to achieve high quality image. This present work proposes an alternative methodology for the generation of the conditional probability distribution associated to the E-M reconstruction algorithm, using the Monte Carlo code MCNP5 and with the application of the reciprocity theorem. (author)

Componential distribution analysis of food using near infrared ray image

Science.gov (United States)

Yamauchi, Hiroki; Kato, Kunihito; Yamamoto, Kazuhiko; Ogawa, Noriko; Ohba, Kimie

2008-11-01

The components of the food related to the "deliciousness" are usually evaluated by componential analysis. The component content and type of components in the food are determined by this analysis. However, componential analysis is not able to analyze measurements in detail, and the measurement is time consuming. We propose a method to measure the two-dimensional distribution of the component in food using a near infrared ray (IR) image. The advantage of our method is to be able to visualize the invisible components. Many components in food have characteristics such as absorption and reflection of light in the IR range. The component content is measured using subtraction between two wavelengths of near IR light. In this paper, we describe a method to measure the component of food using near IR image processing, and we show an application to visualize the saccharose in the pumpkin.

Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry for the Investigation of Proteins and Peptides

Science.gov (United States)

Burnum, Kristin E.; Frappier, Sara L.; Caprioli, Richard M.

2008-07-01

Mass spectrometry (MS) is an excellent technology for molecular imaging because of its high data dimensionality. MS can monitor thousands of individual molecular data channels measured as mass-to-charge (m/z). We describe the use of matrix-assisted laser desorption/ionization (MALDI) MS for the image analysis of proteins, peptides, lipids, drugs, and metabolites in tissues. We discuss the basic instrumentation and sample preparation methods needed to produce high-resolution images and high image reproducibility. Matrix-addition protocols are briefly discussed along with normal operating procedures, and selected biological and medical applications of MALDI imaging MS are described. We give examples of both two- and three-dimensional imaging, including normal mouse embryo implantation, sperm maturation in mouse epididymis, protein distributions in brain sections, protein alterations as a result of drug administration, and protein changes in brain due to neurodegeneration and tumor formation. Advantages of this technology and future challenges for its improvement are discussed.

In Vivo Optical Imaging for Targeted Drug Kinetics and Localization for Oral Surgery and Super-Resolution, Facilitated by Printed Phantoms

Science.gov (United States)

Bentz, Brian Z.

Many human cancer cell types over-express folate receptors, and this provides an opportunity to develop targeted anti-cancer drugs. For these drugs to be effective, their kinetics must be well understood in vivo and in deep tissue where tumors occur. We demonstrate a method for imaging these parameters by incorporating a kinetic compartment model and fluorescence into optical diffusion tomography (ODT). The kinetics were imaged in a live mouse, and found to be in agreement with previous in vitro studies, demonstrating the validity of the method and its feasibility as an effective tool in preclinical drug development studies. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing and evaluation. We present new optical phantoms fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in heterogeneous or anatomically realistic geometries, as opposed to previous phantoms which were limited to simple shapes formed by molds or machining. Furthermore, we show that Mie theory can be used to design the optical properties to match a target tissue. The phantom fabrication methods are versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data. Applications of diffuse optical imaging in the operating theater have been limited in part due to computational burden. We present an approach for the fast localization of arteries in the roof of the mouth that has the potential to reduce complications. Furthermore, we use the extracted position information to fabricate a custom surgical guide using 3D printing that could protect the arteries during surgery. The resolution of ODT is severely limited by the attenuation of high spatial frequencies. We present a super-resolution method achieved through the point localization of fluorescent

Element distribution imaging in rat kidney using a 2 D rapid scan EDXRF device

Energy Technology Data Exchange (ETDEWEB)

Figueroa, R. G. [Universidad de la Frontera, Departamento de Ciencias Fisicas, Av. Francisco Salazar 1145, Temuco 4811230, Araucania (Chile); Lozano, E. [Instituto Nacional del Cancer, Unidad de Fisica Medica, Av. Profesor Zanartu 1010, Santiago (Chile); Bongiovanni, G., E-mail: figueror@ufro.cl [IDEPA-CONICET, Instituto Multidisciplinario de Investigacion y Desarrollo de la Patagonia Norte, Buenos Aires 1400, 8300 Neuquen (Argentina)

2013-08-01

Visualization of elemental distributions of biological tissue is gaining importance in many disciplines of biological, forensic and medical research. Furthermore, the maps of elements have wide application in archaeology for the understanding of the pigments, modes of preservation and environmental context. Since major advances in relation to collimators and detectors have yielded micro scale images, the chemical mapping via synchrotron scanning micro-X-ray fluorescence spectrometry (SR-{mu}X RF) is widely used as microanalytical techniques. However, the acquisition time is a limitation of current SR-{mu}X RF imaging protocols, doing tedious micro analysis of samples of more than 1 cm and very difficult to study of larger samples such as animal organ, whole organisms, work or art, etc. Recently we have developed a robotic system to image the chemistry of large specimens rapidly ar concentration levels of parts per million. Multiple images of distribution of elements can be obtained on surfaces of 100 x 100 mm and a spatial resolution of up to 0.2 mm{sup 2} per pixel, with a spectral capture time up to 1 ms per point. This system has proven to be highly efficient for the X RF mapping of elements in large biological samples, achieving comparable s results to those obtained by SR-{mu}X RF. Thus, images of As and Cu accumulation in renal cortex of arsenic-exposed rats were obtained by both methodologies. However, the new imaging system enables the X RF scanning in few minutes, whereas SR-{mu}X RF required several hours. These and other advantages as well as the potential applications of this system, will be discussed. (Author)