Magnetic Resonance Imaging (MRI) is a non-invasive tool used by the medical community to diagnose disease. Imaging agents, usually chelates, are used to enhance MRI signals. Our study focuses on the physical basis of MRI signal enhancement induced by structural modifications of a novel class of Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) agents. With these agents, the MR image is modified by magnetization transfer between the H₂O molecule bound to the EuIII(DOTA) chelate and bulk water, which is inversely proportional to the rate of H₂O exchange between the bound and bulk H₂O. The water exchange rate depends on the size, the coordination geometry of the lanthanide ion and the electronic properties of the groups attached to the coordinating pendant arm. We present here a computational study of the effect of attaching two pendant arms in either a diagonal or adjacent fashion, rather than having a single pendant arm as well as the effect of chemical modifications of the para-substituents in the coordinating pendant arms on the CEST signal. The effect of simple electron-withdrawing (e.g. nitro) and electron-donating (e.g. methyl) substiuents chemically attached to the chelate arms is quantified by correlating the experimental CEST signal with charge transfer interactions in the coordinated water-chelate system computed from quantum mechanics. This study reveals the origin of the substituent effect on the CEST signal and the electronic structure of the complex.