摘要
MRI is an indispensable diagnostic tool in modern medicine;however,understanding the molecular-level processes governing NMR relaxation of water in the presence of MRI contrast agents remains a challenge,hindering the molecularguided development of more effective contrast agents.By using quantum-based polarizable force fields,the first-of-its-kind molecular dynamics(MD)simulations of Gadobutrol are reported where the ^(1)H NMR longitudinal relaxivity r_(1) of the aqueous phase is determined without any adjustable parameters.The MD simulations of r_(1) dispersion(i.e.,frequency dependence)show good agreement with measurements at frequencies of interest in clinical MRI.Importantly,the simulations reveal key insights into the molecular level processes leading to r_(1) dispersion by decomposing the NMR dipole−dipole autocorrelation function G(t)into a discrete set of molecular modes,analogous to the eigenmodes of a quantum harmonic oscillator.The molecular modes reveal important aspects of the underlying mechanisms governing r_(1),such as its multiexponential nature and the importance of the second eigenmodal decay.By simply analyzing the MD trajectories on a parameter-free approach,the Gadobutrol simulations show that the outer-shell water contributes∼50%of the total relaxivity r_(1) compared to the inner-shell water,in contrast to simulations of(nonchelated)gadolinium-aqua where the outer shell contributes only∼15%of r_(1).The deviation between simulations and measurements of r_(1) below clinical MRI frequencies is used to determine the low-frequency electron-spin relaxation time for Gadobutrol,in good agreement with independent studies.
基金
Ken Kennedy Institute,the Rice University Creative Ventures Fund(Faculty Initiatives Fund)
the Robert A.Welch Foundation for the financial support.
作者简介
Dilipkumar N.Asthagiri,Oak Ridge National Laboratory,Oak Ridge,Tennessee 37830,United States,orcid.org/0000-0001-5869-0807;Steven G.Greenbaum,Department of Physics&Astronomy,Hunter College of the City University of New York,New York,New York 10065,United States,orcid.org/0000-0001-5497-5274;Corresponding Authors:Walter G.Chapman,Department of Chemical and Biomolecular Engineering,Rice University,Houston,Texas 77005,United States,orcid.org/0000-0002-8789-9041,Email:wgchap@rice.edu;Corresponding Authors:Philip M.Singer,Department of Chemical and Biomolecular Engineering,Rice University,Houston,Texas 77005,United States,orcid.org/0000-0003-0061-112X,Email:ps41@rice.edu。
