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Arthur G Palmer - One of the best experts on this subject based on the ideXlab platform.
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Chemical Exchange.
Methods in enzymology, 2018Co-Authors: Arthur G Palmer, Hans KossAbstract:The phenomenon of Chemical or conformational Exchange in NMR spectroscopy has enabled detailed characterization of time-dependent aspects of biomolecular function, including folding, molecular recognition, allostery, and catalysis, on timescales from microsecond to second. Importantly, NMR methods based on a variety of spin relaxation parameters have been developed that provide quantitative information on interconversion kinetics, thermodynamic properties, and structural features of molecular states populated to a fraction of a percent at equilibrium and otherwise unobservable by other NMR approaches. The ongoing development of more sophisticated experimental techniques and the necessity to apply these methods to larger and more complex molecular systems engenders a corresponding need for theoretical advances describing such techniques and facilitating data analysis in applications. This review surveys current aspects of the theory of Chemical Exchange, as utilized in ZZ-Exchange; Hahn and Carr-Purcell-Meiboom-Gill (CPMG) spin-echo; and R1ρ, Chemical Exchange saturation transfer (CEST), and dark state saturation transfer (DEST) spin-locking experiments. The review emphasizes theoretical results for kinetic topologies with more than two interconverting states, both to obtain compact analytical forms suitable for data analysis and to establish conditions for distinguishability between alternative kinetic schemes.
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general expressions for carr purcell meiboom gill relaxation dispersion for n site Chemical Exchange
Biochemistry, 2018Co-Authors: Hans Koss, Mark Rance, Arthur G PalmerAbstract:The Carr–Purcell–Meiboom–Gill (CPMG) nuclear magnetic resonance experiment is widely used to characterize Chemical Exchange phenomena in biological macromolecules. Theoretical expressions for the nuclear spin relaxation rate constant for two-site Chemical Exchange during CPMG pulse trains valid for all time scales are well-known as are descriptions of N-site Exchange in the fast limit. We have obtained theoretical expressions for N-site Exchange outside of the fast limit by using approximations to an average Liouvillian describing the decay of magnetization during a CPMG pulse train. We obtain general expressions for CPMG experiments for any N-site scheme and all experimentally accessible time scales. For sufficiently slow Chemical Exchange, we obtain closed-form expressions for the relaxation rate constant and a general characteristic polynomial for arbitrary kinetic schemes. Furthermore, we highlight features that qualitatively characterize CPMG curves obtained for various N-site kinetic topologies, qua...
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Chemical Exchange in biomacromolecules: past, present, and future.
Journal of magnetic resonance (San Diego Calif. : 1997), 2014Co-Authors: Arthur G PalmerAbstract:The perspective reviews quantitative investigations of Chemical Exchange phenomena in proteins and other biological macromolecules using NMR spectroscopy, particularly relaxation dispersion methods. The emphasis is on techniques and applications that quantify the populations, interconversion kinetics, and structural features of sparsely populated conformational states in equilibrium with a highly populated ground state. Applications to folding, molecular recognition, catalysis, and allostery by proteins and nucleic acids are highlighted.
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Narrowing of protein NMR spectral lines broadened by Chemical Exchange.
Journal of the American Chemical Society, 2010Co-Authors: Arthur G PalmerAbstract:Broadening of spectral lines is a signature of Chemical Exchange phenomena on microsecond to millisecond time scales but has deleterious effects on spectral resolution and sensitivity. A multipulse method based on Chemical shift scaling that reduces Chemical Exchange broadening during frequency-encoding periods of liquid-state multidimensional NMR experiments is described. The proposed scheme utilizes low-power radiofrequency pulses, which offer the advantages of short cycle times and minimal sample heating. The method is suitable for biological macromolecules, as relaxation not resulting from Chemical Exchange is reduced by placing the magnetization along the z axis for part of the evolution trajectory. The resolution and sensitivity enhancement for resonances broadened by Chemical Exchange is demonstrated on the protein ribonuclease A. The work demonstrates the feasibility of applying coherent averaging techniques, which were originally developed in solid-state NMR spectroscopy, to biological NMR spectr...
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characterization of Chemical Exchange using residual dipolar coupling
Journal of the American Chemical Society, 2007Co-Authors: Tatyana I Igumenova, Ulrika Brath, Mikael Akke, Arthur G PalmerAbstract:NMR lineshape analysis and relaxation dispersion measurements for N,N-dimethyltrichloroacetamide (DMTCA) weakly aligned using poly-γ-benzyl-L-glutamate, which forms a lyotropic nematic phase when dissolved in chloroform, were used to characterize Chemical Exchange kinetics for the rotation around the C-N amide bond. At low temperatures ( 312 K), a single population-averaged 13C methyl quartet is observed; in this regime, the differences in RDCs contribute to differential linebroadening of the quartet components. Self-consistent measurements of the difference in RDCs are obtained both from lineshape and relaxation dispersion techniques. The results show that NMR spectroscopy of weakly aligned molecules allow complete characterization of Chemical Exchange processes using RDCs, even if Exchange broadening is absent in isotropic samples.
Phillip Zhe Sun - One of the best experts on this subject based on the ideXlab platform.
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Chemical Exchange Mapping
Advances in Magnetic Resonance Technology and Applications, 2020Co-Authors: Moriel Vandsburger, Phillip Zhe SunAbstract:Abstract Chemical Exchange saturation transfer (CEST) imaging is an emerging MRI technique that provides a sensitive means for the detection of dilute labile proton groups via their Exchange with the abundant bulk tissue water signal. CEST MRI has been applied to investigate biomolecules (e.g., creatine, glutamate, and amide protons) and microenvironment properties (e.g., pH and temperature), with increasing biomedical applications. Whereas CEST-weighted MRI is informative, the development of quantification CEST (qCEST) analysis allows the characterization of the underlying CEST system, including the labile proton concentration and the Chemical Exchange rate. Herein, we provide a comprehensive review of the principle of CEST MRI, its pulse sequence, experimental acquisition, and data analysis, in particular, the measurement of the labile proton Exchange rate.
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quantification of iopamidol multi site Chemical Exchange properties for ratiometric Chemical Exchange saturation transfer cest imaging of ph
Physics in Medicine and Biology, 2014Co-Authors: Phillip Zhe Sun, Dario Livio Longo, Gang XiaoAbstract:pH-sensitive Chemical Exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only Exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent Chemical Exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20?mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed Chemical Exchange for 2-hydrooxypropanamido (ksw = 1.2*10pH?4.1) and amide (ksw = 1.2*10pH?4.6) protons that are statistically different from each other (P?
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Quantification of iopamidol multi-site Chemical Exchange properties for ratiometric Chemical Exchange saturation transfer (CEST) imaging of pH
Physics in medicine and biology, 2014Co-Authors: Phillip Zhe Sun, Dario Livio Longo, Gang XiaoAbstract:pH-sensitive Chemical Exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only Exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent Chemical Exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20?mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed Chemical Exchange for 2-hydrooxypropanamido (ksw = 1.2*10pH?4.1) and amide (ksw = 1.2*10pH?4.6) protons that are statistically different from each other (P?
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imaging ph using the Chemical Exchange saturation transfer cest mri correction of concomitant rf irradiation effects to quantify cest mri for Chemical Exchange rate and ph
Magnetic Resonance in Medicine, 2008Co-Authors: Phillip Zhe Sun, Gregory A SorensenAbstract:Chemical Exchange saturation transfer (CEST) MRI has been shown capable of detecting dilute labile protons and abnormal tissue glucose/oxygen metabolism, and thus, may serve as a complementary imaging technique to the conventional MRI methods. CEST imaging, however, is also dependent on experimental parameters such as the power, duration, and waveform of the irradiation RF pulse. As a result, its sensitivity and specificity for microenvironment properties such as pH is not optimal. In this study, the dependence of CEST contrast on experimental parameters was solved and an iterative compensation algorithm was proposed that corrects the experimentally measured CEST contrast from the concomitant RF irradiation effects. The proposed algorithm was verified with both numerical simulation and experimental measurements from a tissue-like pH phantom, and showed that pH derived from the compensated CEST imaging agrees reasonably well with pH-electrode measurements within 0.1 pH unit. In sum, our study validates the use of a correction algorithm to compensate CEST imaging from concomitant RF irradiation effects for accurate calibration of the Chemical Exchange rate, and demonstrates the feasibility of pH imaging with CEST MRI.
Jinyuan Zhou - One of the best experts on this subject based on the ideXlab platform.
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Chemical Exchange saturation transfer MR imaging of Parkinson's disease at 3 Tesla.
European radiology, 2014Co-Authors: Shuai Peng, Jinyuan Zhou, Rui Wang, Haibo Chen, Xuna Zhao, Min ChenAbstract:Objectives To demonstrate the feasibility of using Chemical Exchange saturation transfer (CEST) imaging to detect Parkinson’s disease (PD) in patients at 3 Tesla.
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Fast 3D Chemical Exchange saturation transfer (CEST) imaging of the human brain.
Magnetic resonance in medicine, 2010Co-Authors: He Zhu, Peter C.m. Van Zijl, Craig K. Jones, Peter B. Barker, Jinyuan ZhouAbstract:Chemical Exchange saturation transfer magnetic resonance imaging can detect low-concentration compounds with Exchangeable protons through saturation transfer to water. This technique is generally slow, as it requires acquisition of saturation images at multiple frequencies. In addition, multislice imaging is complicated by saturation effects differing from slice to slice because of relaxation losses. In this study, a fast three-dimensional Chemical Exchange saturation transfer imaging sequence is presented that allows whole-brain coverage for a frequency-dependent saturation spectrum (z-spectrum, 26 frequencies) in less than 10 min. The approach employs a three-dimensional gradient- and spin-echo readout using a prototype 32-channel phased-array coil, combined with two-dimensional sensitivity encoding accelerations. Results from a homogenous protein-containing phantom at 3T show that the sequence produced a uniform contrast across all slices. To show translational feasibility, scans were also performed on five healthy human subjects. Results for Chemical Exchange saturation transfer images at 3.5 ppm downfield of the water resonance, so-called amide proton transfer images, show that lipid signals are sufficiently suppressed and artifacts caused by B(0) inhomogeneity can be removed in postprocessing. The scan time and image quality of these in vivo results show that three-dimensional Chemical Exchange saturation transfer MRI using gradient- and spin-echo acquisition is feasible for whole-brain Chemical Exchange saturation transfer studies at 3T in a clinical time frame.
Chunyu Wang - One of the best experts on this subject based on the ideXlab platform.
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Solution NMR spin relaxation methods for characterizing Chemical Exchange in high-molecular-weight systems.
Methods in enzymology, 2005Co-Authors: Arthur G Palmer, Michael J. Grey, Chunyu WangAbstract:Abstract Transverse relaxation optimized NMR spectroscopy (TROSY) techniques for 1 H– 15 N backbone amide moieties and for 13 CH 3 methyl groups have permitted the development of Hahn spin echo and Carr–Purcell–Meiboom–Gill (CPMG) experiments for characterizing Chemical Exchange kinetic phenomena on microsecond–millisecond time scales in proteins with molecular masses >50 kDa. This chapter surveys the theoretical bases for TROSY in spin systems subject to Chemical Exchange linebroadening, the experimental methods that have been developed to quantitatively characterize Chemical Exchange in large proteins, and the emerging applications to triose phosphate isomerase, hemoglobin, and malate synthase G, with molecular masses ranging from 54 to 82 kDa.
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Solution NMR methods for quantitative identification of Chemical Exchange in 15N‐labeled proteins
Magnetic Resonance in Chemistry, 2003Co-Authors: Chunyu Wang, Arthur G PalmerAbstract:Chemical Exchange phenomena in NMR spectra reveal protein motions on microsecond to millisecond time scales that are associated with biological functions, including catalysis, ligand binding, allosteric conformational changes and protein folding. This review surveys solution NMR methods for identifying Chemical Exchange in proteins by measuring transverse relaxation rate constants for backbone 15N spins. The relaxation-compensated-IzSz and in-phase Hahn echo methods are suitable for small- to medium-sized proteins. The transverse relaxation optimized spectroscopy method is suitable for large, deuterated proteins. Differential multiple quantum relaxation is also a signature of Chemical Exchange and provides unique information about Exchange processes. The various methods are illustrated by application to basic pancreatic trypsin inhibitor and triosephosphate isomerase. Copyright © 2003 John Wiley & Sons, Ltd.
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Mapping Chemical Exchange in proteins with MW > 50 kD.
Journal of the American Chemical Society, 2003Co-Authors: Chunyu Wang, Mark Rance, Arthur G PalmerAbstract:Chemical Exchange reveals motions in proteins that are critical for ligand binding, catalysis, and allosteric regulation at the microsecond to millisecond time scale. The detection of Chemical Exchange is inherently difficult in large proteins because of the fast transverse relaxation rate (R2) and spectral overlap. Here we report novel pulse sequences for the rapid identification of Chemical Exchange applicable to large deuterated proteins with MW greater than 30 kD. The success of our method is demonstrated in triosephosphate isomerase (TIM, MW = 54 kD).
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Solution NMR methods for quantitative identification of Chemical Exchange in 15N-labeled proteins
Magnetic Resonance in Chemistry, 2003Co-Authors: Chunyu Wang, Arthur G PalmerAbstract:Chemical Exchange phenomena in NMR spectra reveal protein motions on microsecond to millisecond time scales that are associated with biological functions, including catalysis, ligand binding, allosteric conformational changes and protein folding. This review surveys solution NMR methods for identifying Chemical Exchange in proteins by measuring transverse relaxation rate constants for backbone 15N spins. The relaxation-compensated-IzSz and in-phase Hahn echo methods are suitable for small- to medium-sized proteins. The transverse relaxation optimized spectroscopy method is suitable for large, deuterated proteins. Differential multiple quantum relaxation is also a signature of Chemical Exchange and provides unique information about Exchange processes. The various methods are illustrated by application to basic pancreatic trypsin inhibitor and triosephosphate isomerase. Copyright © 2003 John Wiley & Sons, Ltd.
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CPMG sequences with enhanced sensitivity to Chemical Exchange.
Journal of biomolecular NMR, 2001Co-Authors: Chunyu Wang, Michael J. Grey, Arthur G PalmerAbstract:Improved relaxation-compensated Carr-Purcell-Meiboom-Gill pulse sequences are reported for studying Chemical Exchange of backbone 15N nuclei. In contrast to the original methods [J. P. Loria, M. Rance, and A. G. Palmer, J. Am. Chem. Soc. 121, 2331-2332 (1999)], phenomenological relaxation rate constants obtained using the new sequences do not contain contributions from 1H-1H dipole-dipole interactions. Consequently, detection and quantification of Chemical Exchange processes are facilitated because the relaxation rate constant in the limit of fast pulsing can be obtained independently from conventional 15N spin relaxation measurements. The advantages of the experiments are demonstrated using basic pancreatic trypsin inhibitor.
Robert S. Balaban - One of the best experts on this subject based on the ideXlab platform.
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a new class of contrast agents for mri based on proton Chemical Exchange dependent saturation transfer cest
Journal of Magnetic Resonance, 2000Co-Authors: Kathleen M. Ward, Anthony H Aletras, Robert S. BalabanAbstract:Abstract It has been previously shown that intrinsic metabolites can be imaged based on their water proton Exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate Chemical Exchange site that could be developed for use as an exogenous Chemical Exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a Chemical Exchange site on the agent via saturation transfer. The ideal Chemical Exchange site would have a large Chemical shift from water. This permits a high Exchange rate without approaching the fast Exchange limit at physiological pH (6.5–7.6) and temperature (37°C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate Chemicals (amino acids, sugars, nucleotides, heterocyclic ring Chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5,6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best Chemical Exchange site found was the 5.33-ppm indole ring –NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.
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Determination of pH using water protons and Chemical Exchange dependent saturation transfer (CEST).
Magnetic resonance in medicine, 2000Co-Authors: Kathleen M. Ward, Robert S. BalabanAbstract:Solution pH was measured using water proton NMR via Chemical Exchange dependent saturation transfer (CEST) with selected Chemical Exchange sites. Several useful pH-sensitive proton Chemical Exchange agents were found: 5,6-dihydrouracil, 5-hydroxytryptophan, and a combination of 5-hydroxytryptophan and 2-imidazolidinethione. A ratiometric approach was developed that permitted pH determinations that were independent of water T(1) or Exchange site concentration.
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A new class of contrast agents for MRI based on proton Chemical Exchange dependent saturation transfer (CEST).
Journal of magnetic resonance (San Diego Calif. : 1997), 2000Co-Authors: Kathleen M. Ward, Anthony H Aletras, Robert S. BalabanAbstract:It has been previously shown that intrinsic metabolites can be imaged based on their water proton Exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate Chemical Exchange site that could be developed for use as an exogenous Chemical Exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a Chemical Exchange site on the agent via saturation transfer. The ideal Chemical Exchange site would have a large Chemical shift from water. This permits a high Exchange rate without approaching the fast Exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate Chemicals (amino acids, sugars, nucleotides, heterocyclic ring Chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best Chemical Exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.