Schematic of MT pathways and select MT experiments. (A) Protons are coupled by 1) dipolar induced cross-relaxation (red arrows), a through-space MT mechanism that does not involve physical rearrangement; or 2) chemical rearrangement (blue arrows) involving physical motion of protons. MRI-invisible moieties are surrounded by water (MRI observable). (B and C) Schematic of proton NMR spectrum (not to scale) showing spectral lines of chemically exchanging group (e.g., –OH), water, and dipolar cross-relaxation coupled group (e.g., –CH). RF saturation is applied either at –OH resonance (blue arrow) leading to CEST effect (D) or at –CH resonance (red arrow) leading to NOE effect (E). While only –OH and –CH groups are shown here for the sake of simplicity, other exchanging or coupled protons can be used. Only the basic of possible pathways are depicted.