Spectroscopic signals which emanate from complexes between paramagnetic lanthanide III ions (e.g., Tm³⁺) and macrocyclic chelates (e.g., 1,4,7,10-tetramethyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, or DOTMA⁴⁻) are sensitive to physiology (e.g., temperature and/or pH). Because non-exchanging protons from these lanthanide-based macrocyclic agents have relaxation times on the order of a few milliseconds, rapid data acquisition is possible with chemical shift imaging (CSI). Thus Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) which originate from non-exchanging protons of these paramagnetic agents, but exclude water proton detection, can allow molecular imaging. Previous 2D CSI experiments with such lanthanide-based macrocyclics allowed acquisition from ~12 µL voxels in rat brain within 5 minutes using rectangular encoding of k-space. Because cubical encoding of k-space in 3D for whole brain coverage increases CSI acquisition time to several tens of minutes or more, a faster CSI technique is required for BIRDS to be of practical use. Here we demonstrate a CSI acquisition method to improve 3D molecular imaging capabilities with lanthanide-based macrocyclics. Using TmDOTMA⁻, we show datasets from a 20×20×20 mm³ field-of-view with voxels of ~1 µL effective volume acquired within 5 minutes (at 11.7T) for temperature mapping. By employing reduced spherical encoding with Gaussian weighting (RESEGAW) instead of cubical encoding of k-space, a significant increase in CSI signal is obtained. In vitro and in vivo 3D CSI data with TmDOTMA⁻, and presumably similar lanthanide-based macrocyclics, suggest that acquisition using RESEGAW can be used for high spatiotemporal molecular mapping with BIRDS.