Manganese-Enhanced MRI: Biological Applications in Neuroscience

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.

• Publication year

  2015

• Venue

  Frontiers in Neurology

• Publication date

  2015-07-10

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.3389/fneur.2015.00161PMID 26217304PMCID 4498388
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Investigation of the pruritus‐induced functional activity in the rat brain using manganese‐enhanced MRI

  2015cited by this paper
• Axonal transport rate decreased at the onset of optic neuritis in EAE mice

  2014cited by this paper
• Impact of manganese on primary hippocampal neurons from rodents

  2014cited by this paper
• In vivo axonal transport deficits in a mouse model of fronto-temporal dementia

  2014cited by this paper
• Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

  2014cited by this paper
• Repeated amphetamine treatment alters spinal magnetic resonance signals and pain sensitivity in mice.

  2014cited by this paper
• Manganese-enhanced magnetic resonance imaging investigation of the interferon-α model of depression in rats.

  2014cited by this paper
• Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats.

  2014cited by this paper
• Reduced hippocampal manganese-enhanced MRI (MEMRI) signal during pilocarpine-induced status epilepticus: edema or apoptosis?

  2014cited by this paper
• Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging

  2013cited by this paper
• Contrast agents for MRI.

  2013cited by this paper
• Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese‐enhanced MRI

  2013cited by this paper
• The importance of water exchange rates in the design of responsive agents for MRI.

  2013cited by this paper
• Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing therapies

  2013cited by this paper
• Manganese-enhanced MRI reflects seizure outcome in a model for mesial temporal lobe epilepsy

  2013cited by this paper
• In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles.

  2012cited by this paper
• Dose dependence and temporal evolution of the T1 relaxation time and MRI contrast in the rat brain after subcutaneous injection of manganese chloride

  2012cited by this paper
• Manganese‐enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy

  2012cited by this paper
• Using manganese-enhanced MRI to understand BOLD

  2012cited by this paper
• Is there a path beyond BOLD? Molecular imaging of brain function

  2012influential reference
• Manganese-enhanced magnetic resonance imaging in the acute phase of the pilocarpine-induced model of epilepsy.

  2012cited by this paper
• Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl2 administration using osmotic pumps.

  2012cited by this paper
• Impact of Manganese on and Transfer across Blood-Brain and Blood-Cerebrospinal Fluid Barrier in Vitro*

  2012cited by this paper
• Neonatal inflammatory pain increases hippocampal neurogenesis in rat pups.

  2011cited by this paper
• A half century of experimental neuroanatomical tracing.

  2011cited by this paper
• Functional tracing of medial nociceptive pathways using activity‐dependent manganese‐enhanced MRI

  2011cited by this paper
• Functional mapping of rat brain activation following rTMS using activity-induced manganese-dependent contrast

  2011cited by this paper
• Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl₂: hippocampal signal enhancement without disruption of hippocampus-dependent behavior.

  2011cited by this paper
• Manganese enhanced MRI (MEMRI): neurophysiological applications

  2011cited by this paper
• Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults

  2011cited by this paper
• Manganese-enhanced magnetic resonance imaging.

  2011cited by this paper
• Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate.

  2011cited by this paper
• Fractionated manganese injections: effects on MRI contrast enhancement and physiological measures in C57BL/6 mice

  2010cited by this paper
• Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI.

  2010cited by this paper
• Hyperglycemia Induces Oxidative Stress and Impairs Axonal Transport Rates in Mice

  2010cited by this paper
• Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

  2010cited by this paper
• Activity-induced manganese-dependent functional MRI of the rat visual cortex following intranasal manganese chloride administration.

  2010cited by this paper
• Retinal ion regulation in a mouse model of diabetic retinopathy: natural history and the effect of Cu/Zn superoxide dismutase overexpression.

  2009cited by this paper
• Manganese-enhanced MRI of layer-specific activity in the visual cortex from awake and free-moving rats

  2009cited by this paper
• Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in the rat brain are consistent with the tissue‐clearance rates of elemental manganese

  2009cited by this paper
• Accounting for nonspecific enhancement in neuronal tract tracing using manganese enhanced magnetic resonance imaging.

  2009cited by this paper
• Manganese-enhanced magnetic resonance imaging of hypoxic-ischemic brain injury in the neonatal rat

  2009cited by this paper
• Behavioral characterization of pentylenetetrazol-induced seizures in the marmoset.

  2008cited by this paper
• Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

  2008cited by this paper
• Manganese enhanced MRI detects mossy fiber sprouting rather than neurodegeneration, gliosis or seizure-activity in the epileptic rat hippocampus

  2008cited by this paper
• Magnetic resonance imaging of cortical connectivity in vivo

  2008cited by this paper
• Cerebrospinal fluid to brain transport of manganese in a non-human primate revealed by MRI.

  2008cited by this paper
• Statistical mapping of sound-evoked activity in the mouse auditory midbrain using Mn-enhanced MRI

  2008cited by this paper
• Age-related decrease in axonal transport measured by MR imaging in vivo

  2008cited by this paper
• Imaging Appetite-Regulating Pathways in the Central Nervous System Using Manganese-Enhanced Magnetic Resonance Imaging

  2008cited by this paper
• Manganese‐enhanced MRI detection of neurodegeneration in neonatal hypoxic‐ischemic cerebral injury

  2008cited by this paper
• Contrast agents for MRI

  2008cited by this paper
• Detection of cortical gray matter lesion in the late phase of mild hypoxic-ischemic injury by manganese-enhanced MRI

  2008cited by this paper
• Fractionated manganese‐enhanced MRI

  2008cited by this paper
• Repetitive Nociceptive Stimuli in Newborn Rats Do Not Alter the Hippocampal Neurogenesis

  2008cited by this paper
• Manganese and epilepsy: a systematic review of the literature.

  2007cited by this paper
• Manganese‐enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl2: Changes in T1 relaxation times during postnatal development

  2007cited by this paper
• Manganese-enhanced MRI detected the gray matter lesions in the late phase of mild hypoxic-ischemic injury in neonatal rat

  2007cited by this paper
• Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

  2007cited by this paper
• Manganese‐enhanced MRI in a rat model of Parkinson's disease

  2007cited by this paper
• Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI

  2007cited by this paper
• Central neural activity in rats with tinnitus evaluated with manganese-enhanced magnetic resonance imaging (MEMRI).

  2007cited by this paper
• In vivo mapping of temporospatial changes in manganese enhancement in rat brain during epileptogenesis

  2007cited by this paper
• Manganese-enhanced MRI: an exceptional tool in translational neuroimaging.

  2007cited by this paper
• MRI contrast agents for functional molecular imaging of brain activity.

  2007cited by this paper
• In vivo axonal transport rates decrease in a mouse model of Alzheimer's disease

  2007cited by this paper
• Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T1 mapping

  2006cited by this paper
• Tracing neural circuits in vivo with Mn-enhanced MRI.

  2006cited by this paper
• Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI.

  2006cited by this paper
• Hippocampal T2 Signal Change during Amygdala Kindling Epileptogenesis

  2006cited by this paper
• Status Epilepticus in 12‐day‐old Rats Leads to Temporal Lobe Neurodegeneration and Volume Reduction: A Histologic and MRI Study

  2006cited by this paper
• Assessment of the progressive nature of cell damage in the pilocarpine model of epilepsy.

  2006cited by this paper
• Manganese distribution across the blood-brain barrier. IV. Evidence for brain influx through store-operated calcium channels.

  2005cited by this paper
• In vivo auditory brain mapping in mice with Mn-enhanced MRI

  2005cited by this paper
• In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride

  2005cited by this paper
• Manganese‐enhanced magnetic resonance imaging of mouse brain after systemic administration of MnCl2: Dose‐dependent and temporal evolution of T1 contrast

  2005cited by this paper
• [18F]FDOPA PET and clinical features in parkinsonism due to manganism

  2005cited by this paper
• Manganese toxicity upon overexposure

  2004cited by this paper
• In vivo, trans‐synaptic tract‐tracing utilizing manganese‐enhanced magnetic resonance imaging (MEMRI)

  2004cited by this paper
• Differential effects of testosterone on neuronal populations and their connections in a sensorimotor brain nucleus controlling song production in songbirds: a manganese enhanced-magnetic resonance imaging study

  2004cited by this paper
• Progression of Brain Damage after Status Epilepticus and Its Association with Epileptogenesis: A Quantitative MRI Study in a Rat Model of Temporal Lobe Epilepsy

  2004cited by this paper
• Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds

  2004cited by this paper
• Manganese‐enhanced magnetic resonance imaging (MEMRI) of mouse brain development

  2004cited by this paper
• Manganese enhanced magnetic resonance imaging.

  2004cited by this paper
• Manganese Neurotoxicity

  2004cited by this paper
• Functional mapping of neural pathways in rodent brain in vivo using manganese‐enhanced three‐dimensional magnetic resonance imaging

  2004cited by this paper
• Direct CSF injection of MnCl2 for dynamic manganese‐enhanced MRI

  2004influential reference
• Manganese‐enhanced magnetic resonance imaging (MEMRI) of brain activity and applications to early detection of brain ischemia

  2004cited by this paper
• In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI

  2004cited by this paper
• Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

  2004cited by this paper
• In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted MRI during lithium-pilocarpine-induced status epilepticus in the rat.

  2004cited by this paper
• In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2

  2004cited by this paper
• Serial MRI after experimental febrile seizures: Altered T2 signal without neuronal death

  2004cited by this paper
• Manganese distribution across the blood-brain barrier III. The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake.

  2004cited by this paper
• Quantitative MRI of the brain—measuring changes caused by disease

  2004cited by this paper
• In vivo trans‐synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI)

  2003cited by this paper
• Manganese action in brain function.

  2003cited by this paper
• Manganese distribution across the blood-brain barrier. I. Evidence for carrier-mediated influx of managanese citrate as well as manganese and manganese transferrin.

  2003cited by this paper
• NMR studies of structure and function of biological macromolecules (Nobel Lecture)*

  2003cited by this paper
• In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2

  2002cited by this paper

• Exploring manganese-loaded nanoparticle formulations as contrast agents: A comprehensive in vitro and in vivo study.

  2026cites this paper
• Monitoring Cortical Spreading Depolarization: Advancements and Applications in Neurocritical Care: A Scoping Review

  2025cites this paper
• Parental high-fat/high-sugar diets and their lasting impact on brain development in offspring: a longitudinal mouse MRI study

  2025cites this paper
• Micro and macro structural brain plastic changes induced by sexual experience in male rats

  2025cites this paper
• Imaging strategies to assess efficacy and safety of ultrasound-induced blood-brain barrier opening

  2025cites this paper
• Using Manganese-Enhanced MRI to visualize Magnetogenetic-based Neuromodulation

  2025cites this paper
• Metal ions in biomedically relevant macromolecular structures

  2024cites this paper
• Fgf17: A regulator of the mid/hind brain boundary in mammals.

  2024cites this paper
• Neonatal nociceptive stimulation results in pain sensitization, reduction of hippocampal 5-HT1A receptor, and p-CREB expression in adult female rats.

  2024cites this paper
• Magnetic resonance imaging to assess the brain response to fasting in glioblastoma-bearing rats as a model of cancer anorexia

  2023cites this paper
• Therapeutic application of manganese-based nanosystems in cancer radiotherapy.

  2023cites this paper
• Mn-Based Methacrylated Gellan Gum Hydrogels for MRI-Guided Cell Delivery and Imaging

  2023cites this paper
• Longitudinal manganese‐enhanced magnetic resonance imaging of neural projections and activity

  2022cites this paper
• The Role of the Dentate Gyrus in Mediating Hippocampal Functions: The Healthy Brain

  2022cites this paper
• The Role of the Dentate Gyrus in Mediating Hippocampal Functions: The Epileptic Brain

  2022cites this paper
• A Mouse Holder for Awake Functional Imaging in Unanesthetized Mice: Applications in 31P Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, and Resting-State Functional Magnetic Resonance Imaging

  2022cites this paper
• Further perspectives and challenges

  2022cites this paper
• Neuronal hibernation following hippocampal demyelination

  2021cites this paper
• Chronic intestinal inflammation suppresses brain activity by inducing neuroinflammation in mice.

  2021cites this paper
• The BBB surrounds cerebral microvessels and tightly regulates the influx and efflux of molecules circulating in the bloodstream, hindering the delivery of pharmacological agents

  2021cites this paper
• Contrast-Free Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening Using Diffusion Tensor Imaging

  2020cites this paper
• Mapping accumulative whole-brain activities during environmental enrichment with manganese-enhanced magnetic resonance imaging

  2020cites this paper
• Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

  2020cites this paper
• New Therapies to Prevent or Cure Auditory Disorders

  2020cites this paper
• New Automatic and Robust Measures to Evaluate Hearing Loss and Tinnitus in Preclinical Models

  2020cites this paper
• Quantitative analysis of the focused ultrasound-induced blood-brain barrier opening with applications in neurodegenerative disorders

  2020cites this paper
• The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

  2020cites this paper
• Adult brain activation in response to pain is changed by neonatal painful stimulation according to sex: A manganese‐enhanced MRI study

  2020cites this paper
• The cerebellar (para)flocculus: A review on its auditory function and a possible role in tinnitus.

  2020cites this paper
• Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

  2020cites this paper
• Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.

  2020cites this paper
• Manganese-Enhanced MRI of the Brain in Healthy Volunteers

  2019cites this paper
• A schizophrenia risk locus alters brain metal transport and plasma glycosylation

  2019cites this paper
• The neural response to deep brain stimulation of the anterior nucleus of the thalamus: A MEMRI and c-Fos study.

  2019cites this paper
• MRI: An Ideal Tool to Explore the Neural Substrate of Vocal Communication in Songbirds

  2018cites this paper
• MRI Tracking of iPS Cells-Induced Neural Stem Cells in Traumatic Brain Injury Rats

  2018cites this paper
• Anterograde Transport in Axons of the Retinal Ganglion Cells and its Relationship to the Intraocular Pressure during Aging in Mice with Hereditary Pigmentary Glaucoma

  2018cites this paper
• Contributions of a high-fat diet to Alzheimer's disease-related decline: A longitudinal behavioural and structural neuroimaging study in mouse models

  2018cites this paper
• Is Mossy Fiber Sprouting a Potential Therapeutic Target for Epilepsy?

  2018cites this paper
• From Systemic Inflammation to Neuroinflammation: The Case of Neurolupus

  2018cites this paper
• Recent Progress on Manganese-Based Nanostructures as Responsive MRI Contrast Agents.

  2018cites this paper
• Age‐related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice

  2017cites this paper
• Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats.

  2017cites this paper
• Continuous infusion of manganese improves contrast and reduces side effects in manganese‐enhanced magnetic resonance imaging studies

  2017cites this paper
• Next-generation probes, particles, and proteins for neural interfacing

  2017cites this paper
• Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes

  2017cites this paper
• Activity Dependent Changes In Functional And Morphological Characteristics Among Presympathetic Neurons Of The Rostral Ventrolateral Medulla

  2017cites this paper
• Neuroimaging in animal models of epilepsy.

  2017cites this paper
• Use of contrast media in computed tomography and magnetic resonance imaging in horses: Techniques, adverse events and opportunities

  2017cites this paper
• Metal Imaging in the Brain

  2017cites this paper
• Increased activity in respiratory-related nuclei may reflect compensatory mechanisms DBA / 1 imaging data are consistent with imaging changes in human SUDEP

  2017cites this paper
• Multi-system state shifts and cognitive deficits induced by chronic morphine during abstinence.

  2017cites this paper
• Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

  2017cites this paper
• MEMRI is a biomarker defining nicotine-specific neuronal responses in subregions of the rodent brain.

  2017cites this paper
• Manganese-enhanced MR imaging of brain activation evoked by noxious peripheral electrical stimulation.

  2016cites this paper
• Protection by Edaravone, a Radical Scavenger, against Manganese‐Induced Neurotoxicity in Rats

  2016cites this paper
• Healthy Volunteers Manganese-Enhanced MRI of the Brain in

  year unknowncites this paper