Manganese Enhanced MRI for Use in Studying Neurodegenerative Diseases

Abstract

MRI has been extensively used in neurodegenerative disorders, such as Alzheimer’s disease (AD), frontal-temporal dementia (FTD), mild cognitive impairment (MCI), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). MRI is important for monitoring the neurodegenerative components in other diseases such as epilepsy, stroke and multiple sclerosis (MS). Manganese enhanced MRI (MEMRI) has been used in many preclinical studies to image anatomy and cytoarchitecture, to obtain functional information in areas of the brain and to study neuronal connections. This is due to Mn2+ ability to enter excitable cells through voltage gated calcium channels and be actively transported in an anterograde manner along axons and across synapses. The broad range of information obtained from MEMRI has led to the use of Mn2+ in many animal models of neurodegeneration which has supplied important insight into brain degeneration in preclinical studies. Here we provide a brief review of MEMRI use in neurodegenerative diseases and in diseases with neurodegenerative components in animal studies and discuss the potential translation of MEMRI to clinical use in the future.

Longitudinal MEMRI analysis of brain phenotypes in a mouse model of Niemann-Pick Type C disease

“…In addition to mass and volume effects, differences in cellular-level Mn 2+ uptake mechanisms in the context of neurodegenerative disease have been reported ( Saar and Koretsky, 2019 ). Hyperintensity in T1-weighted MEMRI has been attributed to astrogliosis in models of inflammation post ischemic stroke ( Kawai et al, 2010 ) and late stage Parkinson’s disease ( Olson et al, 2016 ), and to aberrant Ca 2+ channel activity in models of multiple sclerosis ( Boretius et al, 2008 ).…”

Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

“…An animal model of PD was established using MPTP (1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine) to induce dopaminergic (DAergic) neuron death in the SNc (114). In rats with MPTP-induced PD, MPTP injury resulted in a decrease in neuronal activity and density in the nigrostriatal DAergic system and CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, as well as a decrease in neurogenesis in the DG, but an increase in the activity of the subthalamic nucleus (STN).…”

“…Animal models of temporal lobe epilepsy include kainic acid (KA)-, pilocarpine-, and pentylenetetrazol-induced epilepsy models, which are divided into an acute phase and a latent phase. Different stages of disease development are associated with different neurobiological changes, such as hippocampal sclerosis, mossy fiber sprouting, inflammation, and neurodegeneration (114).…”

New Strategies in the Design of Paramagnetic CAs

“…Mehdizadeh et al investigated the behaviour in vivo of manganese oxide NPs, highlighting how they can interact with the nervous system leading to tau protein folding and neural death [ 67 ]. Despite this drawback related to the use of Mn, a renewed interest in a branch of MRI called MEMRI (Manganese-enhanced MRI) has grown as a technique for three specific uses: to obtain functional information about the brain or heart, to trace neuronal activity and axonal transport rates and to enhance brain anatomy and cytoarchitecture [ 68 – 70 ]. Indeed, unlike Gd which remains extracellular, the Mn influx and intracellular accumulation through voltage-gated calcium channels can be used to monitor changes in organ conditions giving back signal intensities that depend on cellular density.…”