Off-resonance experiments and contrast agents to improve magnetic resonance imaging (original) (raw)
Inorganic Chemistry, 2018
The relaxivity of Gd(HP-DO3A) was studied as a function of pH and buffer composition in order to identify the main factors of the observed relaxation enhancement due to the exchange of the coordinated hydroxyl proton. It was established that the paramagnetic relaxation time, T 1M , of the coordinated hydroxyl proton is about 50% shorter than that of the protons in the coordinated water molecule. The control of the pK of the coordinated alcoholic −OH moiety in the ligand is fundamental to utilize the proton exchange enhanced relaxivity under physio/pathologic conditions. A new derivative of Gd(HP-DO3A) was synthesized by replacing the −CH 3 group with a −CF 3 moiety. In this complex, the −OH group becomes more acidic. Consequently, the maximum contribution of the proton exchange to the relaxivity is shifted to a lower pH region with the fluorinated ligand.
Studies of factors affecting the design of NMR contrast agents: manganese in blood as a model system
Magnetic Resonance in Medicine, 1984
Some factors affecting the performance of paramagnetic ions as contrast agents for proton NMR imaging have been studied. It is demonstrated that the relaxation rate of an aqueous solution of the ion is not reliably predicted by its magnetic moment, but that significant relaxation enhancement may result when the ion is complexed with large molecules, which increases the dominant correlation time. This enhancement in turn can be altered by factors such as pH and competition for binding. Chelation of the paramagnetic ion, which may be implemented to lower its toxicity, can considerably reduce its efficacy by not only limiting its access to water but also by preventing the enhancement from associations and macromolecules. For manganese the ratio TI /T2 is a useful parameter which is sensitive to the degree of metal binding. These features of paramagnetic relaxation enhancement in tissue are demonstrated in a series of experiments on systems consisting of blood components and manganese.
European Journal of Radiology, 2008
We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T(1) and T(2) of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH(e)) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH(e), independent of water relaxivity, diffusion or exchange.
Trends in NMR studies of paramagnetic Gd(III) complexes as potential contrast agents in MRI
Magnetic Resonance Imaging, 1991
The paramagnetic Gd(II1) complexes with polyaminocarboxylate ligands are intensively studied as possible Contrast Agents for Magnetic Resonance Imaging (M.R.I.). Their ability to enhance the solvent proton relaxation rate is mainly determined by the molecular reorientational time (T,&. In order to increase vR we studied the formation of non-covalent interactions between functionalized Gd(III)-complexes and micelles. The N.M.R.D. (Nuclear Magnetic Relaxation Dispersion) profiles of aqueous solutions of these paramagnetic complexes with hexadecyltrimetbylammonium bromide (CTABr) were measured and the results could be accounted for by difference in negative charge and number of hydrophobic aromatic residues among the different complexes.
Investigation of magnetic properties of various complexes prepared as contrast agents for MRI
Journal of Molecular Structure, 2008
In this study, the relaxivities of various ferri-ferro and superparamagnetic particles in human serum and deionized water were determined by using MRI system operating at 1.5 T. For this purpose, the spin-lattice (1/T 1) and spin-spin (1/T 2) relaxation rates in serum and deionized water were measured versus increasing concentrations of the DyPO 4 , 5Fe 2 O 3 3Gd 2 O 3 + dextran, 5Fe 2 O 3 3Gd 2 O 3 + CMC, 5Fe 2 O 3 3Gd 2 O 3. The longitudinal relaxivity (r 1) and transverse relaxivity (r 2) of proton were determined from the slopes of fits between the relaxation rates and concentrations. T 1 and T 2 times in serum were decreased due to increased concentrations of the ions added to samples. The r 2 /r 1 values for ions added to serum ranged from 1 to 4, whereas the r 2 /r 1 for the ions added to water changed between 0.57 and 1 except that for 5Fe 2 O 3 3Gd 2 O 3. PRRE (proton relaxation rate enhancement) data reveals that, the ions added to serum are not bound to the proteins. The present results suggest that chemical compounds of iron oxide studied may have a potential that can be used as an alternative superparamagnetic MRI contrast agent.
Inorganic Chemistry Communications, 2002
A new global analysis of EPR, 17O NMR relaxation and chemical shift and 1H NMRD profiles with physically meaningful parameters for [Gd(DOTA)(H2O)]− and for [Gd(DTPA)(H2O)]2− in aqueous solution is presented (DOTA=1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)-cyclododecane; DTPA=diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid). The recent developments of an improved EPR relaxation theory, the inclusion of the internal motion of the bound water molecule are the principal modifications. Furthermore the better knowledge of the quadrupolar coupling constant of the bound water molecule, the neglect of the outer-sphere contribution to the chemical shift and the consideration of different isomers for the DOTA complex allowed for an improved analysis. The water exchange and parameters of rotational motion are only slightly changed. Comparison of the contributions of static zero-field-splitting shows that a more symmetric environment of the Gd(III) ion should lead to slower electron spin relaxation, a feature which can become important if all other parameters (rotational correlation time and water exchange rate) are optimised. In the actual stage the improved combined analysis of Gd(III) poly(amino carboxylate) is limited by the approximations of Redfield’s relaxation theory, i.e., very low frequency NMRD-data and slowly tumbling complexes cannot be analysed with the method presented.
Inorganic Chemistry, 2021
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial-ShareAlike| 4.0 International License
Amplification strategies in MR imaging: Activation and accumulation of sensing contrast agents (SCAs
Journal of Magnetic Resonance Imaging, 2006
We review new strategies for the development of Gd3+-based T1-relaxation agents and paramagnetic chemical exchange saturation transfer (PARACEST) “sensing” contrast agents (SCAs) designed specifically to detect small molecules or enzymatic activity in living systems. The first class of agents exhibits molecular “sensing” properties as a result of water coordination sphere effects, cleavage, or synthesis of reactive precursor compounds that recombine with macromolecules with the resultant formation of immobilized or rotationally constrained paramagnetic cations. This effect results in changes of water proton relaxation times. The second class (PARACEST) comprises a family of lanthanide-based paramagnetic compounds suitable for CEST imaging. The need for both types of MR agents is justified by efforts to utilize magnetic resonance imaging (MRI) to visualize fine structures in living tissue, and to increase the molecular specificity of MRI. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.
MnDPDP-enhanced magnetization transfer MR imaging: implications for effective liver imaging
Magnetic Resonance Imaging, 2003
The benefit of combining magnetization transfer (MT) MR imaging technique with liver-specific contrast agent manganese dipyridoxyldiphosphate (MnDPDP) was assessed in our experimental investigation. The study was accomplished by imaging a phantom containing serial concentrations of MnDPDP in cross-linked bovine serum albumin (BSA) with various protein concentrations. A 0.1T clinical MR imager with different parameters for MT and conventional MR sequences were used. The combination of an offset frequency of 8 kHz and an amplitude of 25 T produced nearly maximal MT effect for all protein samples either without MnDPDP or with different MnDPDP concentrations. With long TRs (TR Ͼ 200 ms) MT dramatically improved CNR in conjunction with MnDPDP. With short TRs, the gain in CNR with MT was negligible. However, long TRs with increased number of images are beneficial in liver imaging. We conclude that MT like preparation pulse is useful when paramagnetic contrast agents such as MnDPDP are employed.
Inorganic Chemistry, 2021
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial-ShareAlike| 4.0 International License
Use of a paramagnetic substance, colloidal manganese sulfide, as an NMR contrast material in rats
Journal of Nuclear Medicine Official Publication Society of Nuclear Medicine, 1984
Paramagnetic Pharmaceuticals (magnetopharmaceuticals) that are suitably distributed into specific organ systems or diseased sites might be clinically useful for tissue contrast enhancement in nuclear magnetic resonance images. To deter mine whether an insoluble magnetopharmaceutical might be useful in such ser vice, we investigated the effect of a colloidal preparation of manganese sulfide (MnSC) upon liver and lung spin-lattice relaxation times (T-i) in rats following intra venous administration. NMR tissue sample measurements were made at 24 MHz, and showed that after MnSC treatment, liver T1 valuesâ€"and to a lesser extent lung T1 valuesâ€"were depressed below control values. Liver manganese content (as determined by flame atomic absorption spectrophotometry) increased in propor tion to the dose of MnSC, and the reciprocal of the liver T, values also increased in proportion to the dose of MnSC.
Investigative …, 2010
Rationale and objectives-The observed relaxivity of gadolinium based contrast agents has contributions from the water molecule(s) that bind directly to the gadolinium ion (inner-sphere water), long lived water molecules and exchangeable protons that make up the second-sphere of coordination, and water molecules that diffuse near the contrast agent (outer-sphere). Inner-and second-sphere relaxivity can both be increased by optimization of the lifetimes of the water molecules and protons in these coordination spheres, the rotational motion of the complex, and the electronic relaxation of the gadolinium ion. We sought to identify new high relaxivity contrast agents by systematically varying the donor atoms that bind directly to gadolinium to increase inner-sphere relaxivity and concurrently including substituents that influence the second-sphere relaxivity. Methods-Twenty GdDOTA derivatives were prepared and their relaxivity determined in presence and absence of human serum albumin as a function of temperature and magnetic field. Data was analyzed to extract the underlying molecular parameters influencing relaxivity. Each compound had a common albumin-binding group and an inner-sphere donor set comprising the 4 tertiary amine N atoms from cyclen, an α-substituted acetate oxygen atom, two amide oxygen atoms, an inner-sphere water oxygen atom, and a variable donor group. Each amide nitrogen was substituted with different groups to promote hydrogen bonding with second-sphere water molecules. Results-Relaxivites at 0.47T and 1.4T, 37 °C, in serum albumin ranged from 16.0 to 58.1 mM -1 s -1 and from 12.3 to 34.8 mM -1 s -1 respectively. The reduction of inner-sphere water exchange typical of amide donor groups could be offset by incorporating a phosphonate or phenolate oxygen atom donor in the first coordination sphere resulting in higher relaxivity. Amide nitrogen substitution with pendant phosphonate or carboxylate groups increased relaxivity by as much as 88% compared to the N-methyl amide analog. Second-sphere relaxivity contributed as much as 24 mM -1 s -1 and 14 mM -1 s -1 at 0.47 and 1.4T respectively. Conclusions-Water/proton exchange dynamics in the inner-and second-coordination sphere can be predictably tuned by choice of donor atoms and second-sphere substituents resulting in high relaxivity agents.
Structure-Relaxivity Relationships among Targeted MR Contrast Agents
European Journal of Inorganic Chemistry, 2012
Paramagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. Increasing relaxivity enables imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner-sphere and second sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivitry. In this Microreview we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin.