Probing nitric oxide signaling using molecular MRI

Wide field measurements of nitric oxide (NO) signaling could help understand and diagnose the many physiological processes in which NO plays a key role. Magnetic resonance imaging (MRI) can support particularly powerful approaches for this purpose if equipped with molecular probes sensitized to NO and NO-associated targets. In this review, we discuss the development of MRI-detectable probes that could enable studies of nitrergic signaling in animals and potentially human subjects. Major families of probes include contrast agents designed to capture and report integrated NO levels directly, as well as molecules that respond to or emulate the activity of nitric oxide synthase enzymes. For each group, we outline the relevant molecular mechanisms and discuss results that have been obtained in vitro and in animals. The most promising in vivo data described to date have been acquired using NO capture-based relaxation agents and using engineered nitric oxide synthases that provide hemodynamic readouts of NO signaling pathway activation. These advances establish a beachhead for ongoing efforts to improve the sensitivity, specificity, and clinical applicability of NO-related molecular MRI technology.