Pinheiro Dos Santos Thiago J, Fraenza Carla C, de Araujo Lima E Souza Giselle, Pelegano-Titmuss Emilia, Asthagiri Dilipkumar N, Greenbaum Steven G, Chapman Walter G, Singer Philip M
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, United States.
Department of Physics & Astronomy, Hunter College of the City University of New York, New York, New York 10065, United States.
Chem Biomed Imaging. 2025 Apr 9;3(9):615-629. doi: 10.1021/cbmi.4c00080. eCollection 2025 Sep 22.
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 molecular-guided 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 H NMR longitudinal relaxivity of the aqueous phase is determined . The MD simulations of 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 dispersion by decomposing the NMR dipole-dipole autocorrelation function () 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 , 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 compared to the inner-shell water, in contrast to simulations of (nonchelated) gadolinium-aqua where the outer shell contributes only ∼15% of . The deviation between simulations and measurements of below clinical MRI frequencies is used to determine the low-frequency electron-spin relaxation time for Gadobutrol, in good agreement with independent studies.
磁共振成像（MRI）是现代医学中不可或缺的诊断工具；然而，在存在MRI造影剂的情况下，理解控制水中核磁共振（NMR）弛豫的分子水平过程仍然是一项挑战，这阻碍了更有效造影剂的分子导向开发。通过使用基于量子的极化力场，首次报道了钆布醇的分子动力学（MD）模拟，其中确定了水相的H NMR纵向弛豫率。色散（即频率依赖性）的MD模拟与临床MRI感兴趣频率下的测量结果显示出良好的一致性。重要的是，通过将NMR偶极-偶极自相关函数（）分解为一组离散的分子模式，类似于量子谐振子的本征模式，模拟揭示了导致色散的分子水平过程的关键见解。这些分子模式揭示了控制的潜在机制的重要方面，例如其多指数性质和第二本征模式衰减的重要性。通过简单地以无参数方法分析MD轨迹，钆布醇模拟表明，与内壳层水相比，外壳层水对总弛豫率的贡献约为50%，而（未螯合的）钆水合物模拟中，外壳层仅贡献约15%的。低于临床MRI频率的模拟与测量之间的偏差用于确定钆布醇的低频电子自旋弛豫时间，与独立研究结果吻合良好。
