The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). The methods include: (I) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or supermagnetic metal atom or iron, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or supermagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relativity for the polymer relative to an equivalent amount of unpolymerized substrate. The invention also features substrate compositions. Figure (1) is a synthetic pathway used for synthesis of an enzyme-responsive, paramagnetic monomeric substrate.