In vivo, trans-synaptic tract-tracing utilizing manganese-enhanced magnetic resonance imaging (MEMRI)

It is well established that manganese ion (Mn2+) can access neurons through voltage-gated calcium (Ca2+) channels. Based upon this fundamental principle, Mn2+ has long been used in biomedical research as an indicator of Ca2+ influx in conjunction with fluorescent microscopy. Additionally, after entry into neurons, Mn2+ is transported down axons via microtubule based fast axonal transport. Furthermore, Mn2+ is paramagnetic, resulting in a shortening of the spin-lattice relaxation time-constant, T1, which yields positive contrast enhancement in T1-weighted MRI images, specific to tissues where the ion has accumulated. Manganese-enhanced MRI (MEMRI) utilizes a combination of these properties of Mn2+ to trace neuronal pathways in an MRI-detectable manner. The focus of this review will detail some of the current MEMRI tract-tracing methodologies in mice and non-human primates as well as biological applications of MEMRI tract-tracing.