Manganese-Enhanced Magnetic Resonance Imaging

Manganese-enhanced magnetic resonance imaging (MEMRI) relies on contrasts that are due to the shortening of the T ₁ relaxation time of tissue water protons that become exposed to paramagnetic manganese ions. In experimental animals, the technique combines the high spatial resolution achievable by MRI with the biological information gathered by tissue-specific or functionally induced accumulations of manganese. After in vivo administration, manganese ions may enter cells via voltage-gated calcium channels. In the nervous system, manganese ions are actively transported along the axon. Based on these properties, MEMRI is increasingly used to delineate neuroanatomical structures, assess differences in functional brain activity, and unravel neuronal connectivities in both healthy animals and models of neurological disorders. Because of the cellular toxicity of manganese, a major challenge for a successful MEMRI study is to achieve the lowest possible dose for a particular biological question. Moreover, the interpretation of MEMRI findings requires a profound knowledge of the behavior of manganese in complex organ systems under physiological and pathological conditions. Starting with an overview of manganese pharmacokinetics and mechanisms of toxicity, this chapter covers experimental methods and protocols for applications in neuroscience.