Manganese-Enhanced MRI: Biological Applications in Neuroscience

Abstract

Magnetic resonance imaging (MRI) is an excellent non-invasive tool to investigate biological systems. The administration of the paramagnetic divalent ion manganese (Mn2+) enhances MRI contrast in vivo. Due to similarities between Mn2+ and calcium (Ca2+), the premise of manganese-enhanced MRI (MEMRI) is that the former may enter neurons and other excitable cells through voltage-gated Ca2+ channels. As such, MEMRI has been used to trace neuronal pathways, define morphological boundaries, and study connectivity in morphological and functional imaging studies. In this article, we provide a brief overview of MEMRI and discuss recently published data to illustrate the usefulness of this method, particularly in animal models.

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

“…Previous studies have linked the rs13107325 minor allele (T) with brain MRI changes attributed to regional volumetric differences (8,29). Given the paramagnetic properties of Mn and its known effect on MRI relaxation time (30)(31)(32), we hypothesized that the signal change resulted from changes in local concentrations of Mn and related ions. Decreased Mn would result in longer relaxation times of both T1-and T2-weighted images (T1w, T2w); however, longer T1 leads to lower signal intensity on T1w images, while longer T2 leads to increased signal on T2w images.…”

Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice

“…). To enable semiautomatic MRI‐based morphometry, we repeatedly treated the animals with MnCl 2 , whereby Mn 2+ serves as contrast agent since is accumulated in neurons and changes relaxation time of the T1 contrast (Inoue et al, ; Malheiros et al, ). GP and PP mice showed similar body weights throughout the experiment, i.e.…”

Manganese-enhanced MR imaging of brain activation evoked by noxious peripheral electrical stimulation

“…Activity-induced MEMRI takes advantage of the fast influx and slow efflux of Mn 2+ from the brain, so the Mn 2+ accumulation pattern is retained for several days, enabling MRI to be performed after the noxious electrical stimuli. In combination with the basic properties of MEMRI (i.e., the paramagnetic nature of manganese and neural activity-dependent intracellular increases), activity-induced MRI can now be used for various applications including functional mapping of sensory pathways in awake and unrestrained animals [15] Large numbers of electrophysiological studies in non-human primates and other animals have identified nociceptivespecific neurons in different pain-related areas such as the primary and secondary somatosensory cortices, insula, and ACC [11,23,24]. However, a common finding across most of these studies is that nociceptive-specific neurons are distributed throughout the brain [9].…”