Copper is the third most abundant transition metal in the body and is an essential cofactor in numerous enzymes. Improper regulation of this redox active metal is implicated in a number of disease states including Alzheimer's disease, Parkinson's disease, Menkes disease, and Wilson disease. Our interest in the physiological and pathological roles of copper has led to the development of a series of probes for imaging copper in biological settings. This dissertation presents the design, synthesis, and characterization of a number of magnetic resonance imaging (MRI) contrast agents that respond selectively to copper ions via an increase in longitudinal relaxivity (r₁ ). Copper-Gad-1 (CG1) is the first reported MR-based sensor for Cu ²⁺ and displays a modest (41%) increase in r ₁ in response to 1 equiv of Cu²⁺. One limitation of CG1 is that Zn²⁺ interferes with the Cu²⁺ response, which limits its utility in biological settings. A second generation of probes (CG2–CG6) exhibits improved r₁ increases (73-360%) in response to Cu⁺ and/or Cu²⁺ and no sensitivity to Zn²⁺. In particular, CG2 is a Cu⁺ -sensitive probe that displays a 360% r₁ increase in response to Cu⁺. This increase is the largest observed in the literature for metal-responsive MR-based probes. Phantom MR images of CG2 in solution demonstrate the potential of this agent to detect Cu ⁺ using MRI. The presence of biologically relevant anions partially mutes the Cu⁺ response of CG2, so the scaffold was modified to produce CG7, an MR-based Cu⁺ sensor with reduced anion affinity. Incorporated into the CG7 scaffold are additional anionic groups that provide both electronic and steric barriers to anion binding. The CG2 scaffold was also modified to increase the cell permeability of the agent given the expected intracellular localization of Cu⁺ in biological systems. This endeavor has resulted in Arg₈CG2, a Cu⁺-responsive MRI contrast agent with an octaarginine tail installed for increased cell permeability. In vitro studies performed with Arg₈CG2 demonstrate that the octaarginine tail does not interfere with the ability of this agent to respond to Cu⁺. Arg₈CG2 shows great promise for use as a Cu⁺-responsive MRI contrast agent in biological settings.