or environment of water protons in vivo. Such intrinsic contrast can be augmented by the use of
paramagnetic contrast agents in both clinical and experimental settings; however, these agents are
little
more than anatomical reporters which can at best label
individual fluid compartments or distinguish tissues that are magnetically
similar but histologically distinct. To permit a more direct imaging of the
physiological state of cells or organs, we have prepared and tested
several new classes of "smart" MRI contrast agents that change their
influence on nearby water protons in a conditional fashion. The agents
modulate fast water exchange with the paramagnetic center, yielding
distinct "strong" and "weak" relaxivity states. The modualtion is triggered
by two types of biological events: i. enzymatic processing of the agent and,
ii. binding of an intracelluar messenger. These agents represent the first
examples of direct, three dimensional visualization of gene expression and intracellular second messenger
concentration in the form of a 3D MR image.