In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing

One of the main problems in systems biology is to obtain information between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge the applicability of this technique. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. On the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps.Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps