(197bv) Molecular Insights from Simulations on MRI Contrast Agents in Different Chemical Environments

In Magnetic Resonance Imaging (MRI), the nuclear magnetic resonance (NMR) relaxation of protons in water is used to probe the state of bodily tissues. The contrast in these images is enhanced by Gadolinium-based contrast agents (GBCAs) that act by reducing the water proton relaxation time. However, despite the long history of NMR, the molecular-scale processes in NMR and MRI remain poorly understood; the modeling and interpretation of the physics of relaxation still rely on severe assumptions. Further complicating matters, different tissues present different relaxation times due to variation in the physical and chemical environment, including nano-confinement, presence of osmolytes, electrolytes, and dissolved oxygen; the effect of such complexity is also not understood. In this work, we employ quantum and molecular simulations to investigate the effect of osmolytes on the NMR relaxation of gadolinium(III)-aqua complex and Gadavist®. Our simulation results are corroborated and validated by NMR relaxation dispersion measurements. We investigated the roles of urea and TMAO; urea is a well-known denaturant of protein structure, while TMAO has a stabilizing effect on protein structures. Our investigations show that such osmolytes can influence the NMR relaxation of gadolinium(III) complexes. In this presentation we will discuss these results. Further, we will discuss how the NMR relaxation signal can be decomposed into contributions from dynamical “molecular modes,” a technique that can prove powerful in building a library of signals to interpret NMR and MRI signals in otherwise hard to analyze environments.