Computational pipeline for estimation of small-molecule T1 relaxation times.

Molecular imaging of biologic molecules and cellular processes is increasingly accessible through hyperpolarization of chemically-equivalent stable isotopes, most commonly C. However, many molecules are poor candidates for imaging due to their biophysical properties, particularly short spin-lattice relaxation times (T). The inability to consistently predict the T from molecular structure, lack of experimental data for many biologically-relevant molecules and the high cost of developing probes can limit the development of hyperpolarized probes. We describe an in silico pipeline for modeling the estimated T of molecules of interest in order to address this deficiency. Applying a hybrid approach that incorporates molecular dynamics as well as quantum mechanics, this pipeline estimated T values that closely matched empirically determined values providing proof-of-principle that this approach may be used to facilitate MR probe development.