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High Relaxivity Mri Contrast Agents
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Book Synopsis High-Relaxivity MRI Contrast Agents by :
Download or read book High-Relaxivity MRI Contrast Agents written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.
Book Synopsis Contrast Agents I by : Werner Krause
Download or read book Contrast Agents I written by Werner Krause and published by Springer. This book was released on 2003-07-01 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extracellular MRI and X-ray contrast agents are characterized by their phar- cokinetic behaviour.After intravascular injection their plasma-level time curve is characeterized by two phases. The agents are rapidly distributed between plasma and interstitial spaces followed by renal elimination with a terminal half-live of approximatly 1–2 hours. They are excreted via the kidneys in unchanged form by glomerular filtration. Extracellular water-soluble contrast agents to be applied for X-ray imaging were introduced into clinical practice in 1923. Since that time they have proved to be most valuable tools in diagnostics.They contain iodine as the element of choice with a sufficiently high atomic weight difference to organic tissue. As positive contrast agents their attenuation of radiation is higher compared with the attenuation of the surrounding tissue. By this contrast enhancement X-ray diagnostics could be improved dramatically. In 2,4,6-triiodobenzoic acid derivatives iodine is firmly bound. Nowadays diamides of the 2,4,6-triiodo-5-acylamino-isophthalic acid like iopromide (Ultravist, Fig. 1) are used as non-ionic (neutral) X-ray contrast agents in most cases [1].
Book Synopsis MRI Contrast Agents by : Sophie Laurent
Download or read book MRI Contrast Agents written by Sophie Laurent and published by Springer. This book was released on 2016-11-03 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the multiple aspects of (i) preparation of the magnetic core, (ii) the stabilization with different coatings, (iii) the physico-chemical characterization and (iv) the vectorization to obtain specific nanosystems. Several bio-applications are also presented in this book. In the early days of Magnetic Resonance Imaging (MRI), paramagnetic ions were proposed as contrast agents to enhance the diagnostic quality of MR images. Since then, academic and industrial efforts have been devoted to the development of new and more efficient molecular, supramolecular and nanoparticular systems. Old concepts and theories, like paramagnetic relaxation, were revisited and exploited, leading to new scientific tracks. With their high relaxivity payload, the superparamagnetic nanoparticles are very appealing in the context of molecular imaging but challenges are still numerous: absence of toxicity, specificity, ability to cross the biological barriers, etc.
Book Synopsis High Relaxivity Biomolecule Based Contrast Agents Engineered for Molecular Functional Magnetic Resonance Imaging by : Vivian Hsieh (Ph. D.)
Download or read book High Relaxivity Biomolecule Based Contrast Agents Engineered for Molecular Functional Magnetic Resonance Imaging written by Vivian Hsieh (Ph. D.) and published by . This book was released on 2016 with total page 93 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic resonance imaging (MRI) is a powerful neuroimaging tool that allows non-invasive visualization of the brain with high spatial and temporal resolution. Research on MRI contrast agents and their application to problems in neuroscience is burgeoning, and there is particular interest in developing MRI agents that are sensitive to time varying components of neurophysiology. Relatively recent advances in biomolecular probes has demonstrated the potential and versatility of bioengineered MRI sensors for molecular imaging. However, a major limitation of these probes is the high concentration needed for imaging, which can lead to issues such as analyte buffering and toxicity, and restrict the applicability of the sensors. In this work, we explore two approaches for developing high relaxivity protein-based contrast agents to address the issues of low detectability. First, we coupled monoamine sensing with the disaggregation of superparamagnetic iron oxide nanoparticles (SPIOs). Ligand detection was imparted by integration of a monoamine sensing protein-based contrast agent derived from P450- BM3h (BM3). We demonstrated that this mechanism can produce robust signal changes of approximately 2-fold, while reducing the concentration of BM3 needed by 100-fold compared to the amount needed when only the protein is used for imaging. The second method demonstrated the feasibility of using semi-rational protein design to engineer a high relaxivity metalloprotein by tuning phenylalanine hydroxylase to bind gadolinium at high affinity. Mutations were found that increased the protein affinity by two orders of magnitude and enhanced relaxivity. The results of this thesis advance approaches for creating high relaxivity contrast agents which can be applied to the development of probes for other analytes, ultimately advancing and broadening the applicability of bioengineered probes in molecular functional neuroimaging.
Book Synopsis Gd-HOPO Based High Relaxivity MRI Contrast Agents by :
Download or read book Gd-HOPO Based High Relaxivity MRI Contrast Agents written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Tris-bidentate HOPO-based ligands developed in our laboratory were designed to complement the coordination preferences of Gd{sup 3+}, especially its oxophilicity. The HOPO ligands provide a hexadentate coordination environment for Gd{sup 3+} in which all he donor atoms are oxygen. Because Gd{sup 3+} favors eight or nine coordination, this design provides two to three open sites for inner-sphere water molecules. These water molecules rapidly exchange with bulk solution, hence affecting the relaxation rates of bulk water olecules. The parameters affecting the efficiency of these contrast agents have been tuned to improve contrast while still maintaining a high thermodynamic stability for Gd{sup 3+} binding. The Gd- HOPO-based contrast agents surpass current commercially available agents ecause of a higher number of inner-sphere water molecules, rapid exchange of inner-sphere water molecules via an associative mechanism, and a long electronic relaxation time. The contrast enhancement provided by these agents is at least twice that of commercial contrast gents, which are based on polyaminocarboxylate ligands.
Book Synopsis Design and Evaluation of Gadolinium(III) Complexes as High-relaxivity MRI Contrast Agents by : Eric Joseph Werner
Download or read book Design and Evaluation of Gadolinium(III) Complexes as High-relaxivity MRI Contrast Agents written by Eric Joseph Werner and published by . This book was released on 2007 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: The emergence of new instrumentation and applications for Magnetic Resonance Imaging (MRI) invites the development of more efficient contrast agents. Current commercial agents employ gadolinium(III) complexes of polyaminocarboxylate ligands and achieve modest relaxivities (increase in water proton longitudinal relaxation) due to a low number of coordinated water molecules (q = 1) and slow water exchange rates. Raymond and coworkers (University of California, Berkeley) have developed a family of stable hydroxypyridinone (HOPO)-based Gd(III) chelates that show promise as next-generation contrast agents due to an increased hydration number and faster water exchange rates leading to relaxivities that are about twice the values for commercial agents. A unique aspect of these compounds is that, unlike what is observed for currently used clinical agents, the relaxivity does not typically decrease with increasing magnetic field strength (e.g. 3 T).
Book Synopsis High Relaxivity Contrast Agents for Magnetic Resonance Imaging (MRI) by : Marco Giardiello
Download or read book High Relaxivity Contrast Agents for Magnetic Resonance Imaging (MRI) written by Marco Giardiello and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates by :
Download or read book High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates written by and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM−1s−1 at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) there is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ([tau]{sub RI} = 440 ps) and external ([tau]{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.
Book Synopsis High Relaxivity Polymeric MRI Contrast Agents by : Thomas Berki
Download or read book High Relaxivity Polymeric MRI Contrast Agents written by Thomas Berki and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book MRI written by Brian M. Dale and published by John Wiley & Sons. This book was released on 2015-08-06 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fifth edition of the most accessible introduction to MRI principles and applications from renowned teachers in the field provides an understandable yet comprehensive update. Accessible introductory guide from renowned teachers in the field Provides a concise yet thorough introduction for MRI focusing on fundamental physics, pulse sequences, and clinical applications without presenting advanced math Takes a practical approach, including up-to-date protocols, and supports technical concepts with thorough explanations and illustrations Highlights sections that are directly relevant to radiology board exams Presents new information on the latest scan techniques and applications including 3 Tesla whole body scanners, safety issues, and the nephrotoxic effects of gadolinium-based contrast media
Book Synopsis Synthesis of Modular DO3A-based High-relaxivity Contrast Agents for MRI of Prostate Cancer by : Dana Qiang Murphy Soika
Download or read book Synthesis of Modular DO3A-based High-relaxivity Contrast Agents for MRI of Prostate Cancer written by Dana Qiang Murphy Soika and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Contrast agents (CAs) are small molecules used in magnetic resonance imaging (MRI) to help diagnose various forms of cancer. While MRI is advantageous over other clinical imaging techniques, limitations of today’s contrast agents containing gadolinium (Gd) hinder their safety, sensitivity, and specificity. The conventional CAs that MRI relies on are considered low-relaxivity and are not optimally effective at enhancing MR signal. Additionally, they lack cell-specificity and circulate throughout the body. Furthermore, unbound Gd3+ is nephrogenic which prevents its use in patients with impaired renal function. In the clinic, these limitations mean high dosages of these compounds must be administered to patients in order to produce an image that struggles to highlight the exact tumor location. Our aim was to improve conventional CAs by synthesizing a high-relaxivity (HR) targeted contrast agent (HR-TCA). The cell-specific nature of the HR-TCA will allow for its accumulation at tumor sites while the HR will produce a stronger MR signal per molecule of CA. Combined, this means a much lower and therefore safer dose of CA can be used to produce an image of the exact tumor location with superior contrast. Our modular approach allows us to easily combine this HR contrast agent (HR-CA) to any targeting peptide using a linker in a convergent, one-step synthesis. Our synthetic approach for the HR-CA module attaches a macrocyclic chelator, DO3A, to the side chain of an orthogonally protected alanine. This is a modification to the approach published by Boros in which t-butyl groups were utilized to protect DO3A. In our modular approach, Gd is chelated early to protect the acetic acid donor arms of DO3A from participating in unwanted side reactions for the remainder of the synthesis, eliminating any need to expose the final HR-TCA to the harsh acidic conditions of TFA that are necessary to remove t-butyl protecting groups. Upon removal of the N- and C-terminal protecting groups, the HR-CA module is coupled directly to our in-house synthesized targeting module which is comprised of the targeting agent (DCL) and linker (DSS) already attached to afford the final HR- TCA. T1 relaxation measurements of relevant intermediates and the final product were performed to compare their relaxivities with those of commercial CAs used in clinics, labs, and hospitals today. Although the HR-CA and final HR-TCA exhibited only a modest increase in T1 relaxivity compared to commercial CA Gd-DOTA, in a striking discovery it was observed that the presence of both a tryptophan spacer and an Fmoc protecting group boosted the T1 relaxivity significantly."--Abstract.
Book Synopsis The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging by : Andre S. Merbach
Download or read book The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging written by Andre S. Merbach and published by John Wiley & Sons. This book was released on 2013-02-19 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Resonance Imaging (MRI) is one of the most important tools in clinical diagnostics and biomedical research. The number of MRI scanners operating around the world is estimated to be approximately 20,000, and the development of contrast agents, currently used in about a third of the 50 million clinical MRI examinations performed every year, has largely contributed to this significant achievement. This completely revised and extended second edition: Includes new chapters on targeted, responsive, PARACEST and nanoparticle MRI contrast agents. Covers the basic chemistries, MR physics and the most important techniques used by chemists in the characterization of MRI agents from every angle from synthesis to safety considerations. Is written for all of those involved in the development and application of contrast agents in MRI. Presented in colour, it provides readers with true representation and easy interpretation of the images. A word from the Authors: Twelve years after the first edition published, we are convinced that the chemistry of MRI agents has a bright future. By assembling all important information on the design principles and functioning of magnetic resonance imaging probes, this book intends to be a useful tool for both experts and newcomers in the field. We hope that it helps inspire further work in order to create more efficient and specific imaging probes that will allow materializing the dream of seeing even deeper and better inside the living organisms. Reviews of the First Edition: "...attempts, for the first time, to review the whole spectrum of involved chemical disciplines in this technique..."—Journal of the American Chemical Society "...well balanced in its scope and attention to detail...a valuable addition to the library of MR scientists..."—NMR in Biomedicine
Book Synopsis Designing a More Effective MRI Contrast Agent by :
Download or read book Designing a More Effective MRI Contrast Agent written by and published by . This book was released on 2020 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic resonance imaging (MRI) is a medical imaging technique that provides high-resolution images used for diagnostic medicine while maintaining a superior safety profile compared to other radiative techniques. The administration of gadolinium-based contrast agents (GBCAs) improves the diagnostic power of MRI and have been used clinically for over three decades. Although GBCAs are effective at improving the contrast in the image, their detection limits are high and require a large dose to generate an observable effect. This high dose is the consequence of the current available designs of clinical GBCAs; their structures are not tuned to generate optimal efficacy. Efficacy of GBCAs is defined as relaxivity; how effectively the agent increases the T1 relaxation rate constant of protons on water. The isoelectric structure of the f-orbitals of Gd3+ yields it an effective relaxivity agent. However, Gd3+ is toxic and insoluble in vivo, and is therefore bound as a low molecular weight hydrophilic chelate. The ligand which forms the most kinetically inert and safest GBCA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA). Parameters defined by Solomon, Bloembergen, and Morgan (SBM) describe different factors that influence relaxivity of a GBCA. Two of which have been demonstrated to dramatically influence efficacy: chelate tumbling and water exchange rates. A drawback to current ligand systems are low molecular weight; relaxivity increases with slower tumbling chelates. Current GBCAs have a tumbling rate that is much too rapid to achieve high relaxivities. Secondly, while this value is predominating, it is difficult to ascertain the contribution of other SBM parameters. It had been originally hypothesized that to improve relaxivity, water exchange rate needs to be fast. However, research in our group has demonstrated that a chelate which exchanges water too rapidly suffers from a reduction in its hydration state. The implication of this reduction in hydration state on relaxivity has yet to be fully appreciated. The importance of the influence of SBM parameters on relaxivity is realized when advancements in GBCA technology are applied. The non-specific nature of GBCAs means they cannot directly diagnose pathology. One promising approach to reduce detection limits by increasing specificity in vivo is through bifunctional chelators (BFCs). These ligands have two components: a metal chelating group to bind gadolinium (DOTA), and a reactive moiety that couples with a targeting vector to bind desired biological receptors. This allows for defined bioaccumulation in vivo, resulting in improved diagnostics and lower detection limits. But with several BFCs available commercially, each positioning the vector attachment differently on the DOTA scaffold, the ideal scaffold for BFC design while including the influence of SBM is yet to be established. The three most common strategies of targeting vector attachment are off the tetraaza macrocycle, through a monoamide pendant arm, or off an [alpha]-carbon on the acetate pendant arm. A thorough investigation of these three strategies was explored herein, in which BFC precursors were synthesized, and their structures analyzed relaxometrically. It was found that the attachment strategy significantly impacted water exchange parameters and molecular tumbling, which in turn greatly influenced relaxivity. The experiments conducted herein presented compelling new evidence in the way we define water exchange and hydration state. Studies into derivatives of the macrocycle substituted chelate NB-DOTA presented the impact an extremely rapidly exchanging chelate has on hydration state and its effect on relaxivity. Synthesis and analysis of a new tetra [alpha]-carbon substituted chelate, DOTFA, yielded an exceedingly high relaxivity, as well as an interesting and novel impact on water exchange; there is strong evidence that DOTFA chelates exchange water in a mechanism that is not purely dissociative. Finally, studies into amide substituted chelates provided the expected low relaxivity associated with slow water exchange. Yet, it was demonstrated that changing the type of coordinating monoamide pendant arm, water exchange can be tuned to slightly more optimal values. These systematic studies provided novel insight how the most effective targeted GBCA can be designed, synthesized, and analyzed, as well as presented new evidence into the impact functionalization strategies have on relaxometric values.
Book Synopsis Magnetic Nanoparticles in Biosensing and Medicine by : Nicholas J. Darton
Download or read book Magnetic Nanoparticles in Biosensing and Medicine written by Nicholas J. Darton and published by Cambridge University Press. This book was released on 2019-02-14 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drawing together topics from a wide range of disciplines, and featuring up-to-date examples of clinical usage and research applications, this text provides a comprehensive insight into the fundamentals of magnetic biosensors and the applications of magnetic nanoparticles in medicine.
Book Synopsis Synthesis and Relaxivity of a Target-specific MRI Contrast Agent by : Callie Clement
Download or read book Synthesis and Relaxivity of a Target-specific MRI Contrast Agent written by Callie Clement and published by . This book was released on 2018 with total page 74 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis New Strategies for Highly Efficient MRI Contrast Agents by : João Bruno Figueiredo Livramento
Download or read book New Strategies for Highly Efficient MRI Contrast Agents written by João Bruno Figueiredo Livramento and published by . This book was released on 2006 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis NMR Studies of MRI Contrast Agents and Cementitous Materials by : Zihui Peng
Download or read book NMR Studies of MRI Contrast Agents and Cementitous Materials written by Zihui Peng and published by . This book was released on 2013 with total page 99 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nuclear magnetic resonance (NMR) is an important phenomenon involving nuclear magnetic moments in magnetic field, which can provide much information about a wide range of materials, including their chemical composition, chemical environments and nuclear spin interactions. The NMR spectrometer has been extensively developed and used in many areas of research. In this thesis, studies in two different areas using NMR are presented. First, a new kind of nanoparticle, Gd(DTPA) intercalated layered double hydroxide (LDH), has been successfully synthesized in the laboratory of Prof. Dey in SEMTE at ASU. In Chapter II, the NMR relaxation studies of two types of LDH (Mg, Al-LDH and Zn, Al-LDH) are presented and the results show that when they are intercalated with Gd(DTPA) they have a higher relaxivity than current commercial magnetic resonance imaging (MRI) contrast agents, such as DTPA in water solution. So this material may be useful as an MRI contrast agent. Several conditions were examined, such as nanoparticle size, pH and intercalation percentage, to determine the optimal relaxivity of this nanoparticle. Further NMR studies and simulations were conducted to provide an explanation for the high relaxivity. Second, fly ash is a kind of cementitious material, which has been of great interest because, when activated by an alkaline solution, it exhibits the capability for replacing ordinary Portland cement as a concrete binder. However, the reaction of activated fly ash is not fully understood. In chapter III, pore structure and NMR studies of activated fly ash using different activators, including NaOH and KOH (4M and 8M) and Na/K silicate, are presented. The pore structure, degree of order and proportion of different components in the reaction product were obtained, which reveal much about the reaction and makeup of the final product.
