Seminar:

MR imaging offers a non-invasive means to map structure and function by sampling the amount, flow 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 typically anatomical reporters that label individual fluid compartments and distinguish tissues that are magnetically similar but histologically distinct. To permit a direct imaging of the physiological state of cells or organs, we have synthesized and in vivo tested new bio-activated MR imaging contrast probes 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 and are modulated by two types of biological events: i. self-immolative enzymatic processing of the complex that is a reporter probe for lacZ (b-galactosidase and ii. binding of the intracellularmessenger, Ca(II). These agents provide the ability to monitor gene expression and intracellular second messenger activity in the form of acquired 3D MR images.