Manganese-Enhanced Magnetic Resonance Imaging

Abstract

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.

Cocaine‐induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese‐enhanced MRI

“…As discussed, the signal intensity changes observed using MEMRI are dependent on Ca 2+ channel activity (13–16). Therefore, it is reasonable to assume that the increases in cocaine-induced signal activity in the NAC observed in this study are Ca 2+ -dependent and reflect enhanced neuronal activity.…”

“…Given that behavioral studies are performed on awake and freely moving animals, a major advantage of MEMRI is that functional brain activity can also be interrogated in the same rat that underwent drug administration and behavioral testing, thus eliminating the confound of anesthesia exposure. Mn 2+ is an MRI contrast agent as well as a Ca 2+ surrogate which enters excitable cells via L-type Ca 2+ channels (LTCCs), such as Ca v 1.2 (13, 14). Since LTCCs are critical modulators of normal neuronal function, increased neuronal activity is tightly linked with their activity.…”

4D MEMRI atlas of neonatal FVB/N mouse brain development

“…MEMRI has emerged as a unique and effective in vivo imaging approach for a variety of anatomical and functional studies in the mouse brain (Boretius and Frahm, 2011; Chan et al, 2014; Inoue et al, 2011; Koretsky and Silva, 2004; Nieman and Turnbull, 2010; Pautler, 2004, 2006; Silva et al, 2004; Watanabe et al, 2010; Yu et al, 2005). In the developing mouse brain, the increased SNR and contrast due to cellular uptake of paramagnetic Mn ions has made it possible to analyze brain sub-regions and perform morphological phenotype analysis from embryonic to early postnatal stages (Deans et al, 2008; Szulc et al, 2013; Wadghiri et al, 2004).…”

Is there a path beyond BOLD? Molecular imaging of brain function

“…This idea was used to make functional maps of somatosensory areas in brain by Lin et al in the rat brain (Lin et al, 1997). There is now a significant body of work that has used Mn 2+ as a versatile contrast agent to study the brain (Boretius and Frahm, 2011; Inoue et al 2011). There have been a few studies that have demonstrated excellent agreement between MEMRI maps and fMRI maps of neural representations (see Silva in this issue of Neuroimage).…”