Transcranial manganese delivery for neuronal tract tracing using MEMRI

Atanasijević, Tatjana; Bouraoud, Nadia; McGavern, Dorian B.; Koretsky, Alan P.

doi:10.1016/j.neuroimage.2017.05.025

Cited by 8 publications

(6 citation statements)

References 49 publications

(60 reference statements)

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“…Remarkably, transcranial injection of manganese chloride showed detectable manganese signal in the brain parenchyma within 2 h of administration (Roth et al, 2014). More recently, the Koretsky group expanded upon this technique by showing that manganese penetrates into underlying brain structures when applied transcranially by passing through brain suture lines (Atanasijevic et al, 2017). While transcranial application of manganese for MEMRI requires further optimization before widespread use, its potential in relatively noninvasive MEMRI studies are becoming extremely valuable.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Cloyd

Koren

Abisambra

2018

Front. Aging Neurosci.

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Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans.

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Section: Pharmacodynamicsmentioning

confidence: 99%

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Cloyd

Koren

Abisambra

2018

Front. Aging Neurosci.

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“…Alternatively, intranasal administration of MnCl 2 can bypass the blood–brain barrier while enhancing the visual cortex (Fa et al, 2010). It is also possible to assess the neuronal tracts of the visual system directly by transcranial Mn 2+ delivery (Atanasijevic et al, 2017).…”

Section: Routes Of Administrationmentioning

confidence: 99%

“…Bicine and sodium hydroxide can be utilized to adjust pH to around 7.2 to 7.4 (Silva et al, 2004; Bock et al, 2008). Alternatively, for non-invasive Mn 2+ delivery, such as transcranial administration, high osmolarity of MnCl 2 solution at about 250–500 mM is required to pass through the intact rat skull unless CaCl 2 is added to MnCl 2 such that the total salt concentration equals 500 mM (Atanasijevic et al, 2017). It should be noted that retinal degeneration has been reported after intravitreal injection of normal saline but not phosphate-buffered saline to C57BL/6J mice (Hombrebueno et al, 2014).…”

Section: Contrast Agent Preparation and Mri Protocolsmentioning

confidence: 99%

Applications of Manganese-Enhanced Magnetic Resonance Imaging in Ophthalmology and Visual Neuroscience

Deng

Faiq

Liu

et al. 2019

Front. Neural Circuits

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Understanding the mechanisms of vision in health and disease requires knowledge of the anatomy and physiology of the eye and the neural pathways relevant to visual perception. As such, development of imaging techniques for the visual system is crucial for unveiling the neural basis of visual function or impairment. Magnetic resonance imaging (MRI) offers non-invasive probing of the structure and function of the neural circuits without depth limitation, and can help identify abnormalities in brain tissues in vivo . Among the advanced MRI techniques, manganese-enhanced MRI (MEMRI) involves the use of active manganese contrast agents that positively enhance brain tissue signals in T1-weighted imaging with respect to the levels of connectivity and activity. Depending on the routes of administration, accumulation of manganese ions in the eye and the visual pathways can be attributed to systemic distribution or their local transport across axons in an anterograde fashion, entering the neurons through voltage-gated calcium channels. The use of the paramagnetic manganese contrast in MRI has a wide range of applications in the visual system from imaging neurodevelopment to assessing and monitoring neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this review, we present four major domains of scientific inquiry where MEMRI can be put to imperative use — deciphering neuroarchitecture, tracing neuronal tracts, detecting neuronal activity, and identifying or differentiating glial activity. We deliberate upon each category studies that have successfully employed MEMRI to examine the visual system, including the delivery protocols, spatiotemporal characteristics, and biophysical interpretation. Based on this literature, we have identified some critical challenges in the field in terms of toxicity, and sensitivity and specificity of manganese enhancement. We also discuss the pitfalls and alternatives of MEMRI which will provide new avenues to explore in the future.

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“…This pattern of accumulation has been useful for defining cytoarchitecture in a number of brain regions with MRI 2,4,25 . Mn 2+ also defines neural pathways as an anterograde tracer when administered to peripheral sensory systems or by stereotaxic cranial injection 1,3,32 . Finally, Mn 2+ can accumulate in excitable cells such as neurons, cardiac cells, rapidly dividing carcinogenic cells and pancreatic β‐cells based on the membrane potential dependent transport through L‐type voltage‐gated calcium channels (VGCCs) 2,5,33 .…”

Section: Introductionmentioning

confidence: 99%

“…2,4,25 Mn 2+ also defines neural pathways as an anterograde tracer when administered to peripheral sensory systems or by stereotaxic cranial injection. 1,3,32 Finally, Mn 2+ can accumulate in excitable cells such as neurons, cardiac cells, rapidly dividing carcinogenic cells and pancreatic β-cells based on the membrane potential dependent transport through L-type voltage-gated calcium channels (VGCCs). 2,5,33 These three useful properties of MEMRI have led to its widespread use in animal models of normal and diseased tissue like those found in Alzheimer's disease and schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

A hierarchy of manganese competition and entry in organotypic hippocampal slice cultures

et al. 2021

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Contrast agents improve clinical and basic research MRI. The manganese ion (Mn2+) is an essential, endogenous metal found in cells and it enhances MRI contrast because of its paramagnetic properties. Manganese‐enhanced MRI (MEMRI) has been widely used to image healthy and diseased states of the body and the brain in a variety of animal models. There has also been some work in translating the useful properties of MEMRI to humans. Mn2+ accumulates in brain regions with high neural activity and enters cells via voltage‐dependent channels that flux calcium (Ca2+). In addition, metal transporters for zinc (Zn2+) and iron (Fe2+) can also transport Mn2+. There is also transfer through channels specific for Mn2+. Although Mn2+ accumulates in many tissues including brain, the mechanisms and preferences of its mode of entry into cells are not well characterized. The current study used MRI on living organotypic hippocampal slice cultures to detect which transport mechanisms are preferentially used by Mn2+ to enter cells. The use of slice culture overcomes the presence of the blood brain barrier, which limits inferences made with studies of the intact brain in vivo. A range of Mn2+ concentrations were used and their effects on neural activity were assessed to avoid using interfering doses of Mn2+. Zn2+ and Fe2+ were the most efficient competitors for Mn2+ uptake into the cultured slices, while the presence of Ca2+ or Ca2+ channel antagonists had a more moderate effect. Reducing slice activity via excitatory receptor antagonists was also effective at lowering Mn2+ uptake. In conclusion, a hierarchy of those agents which influence Mn2+ uptake was established to enhance understanding of how Mn2+ enters cells in a cultured slice preparation.

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Transcranial manganese delivery for neuronal tract tracing using MEMRI

Cited by 8 publications

References 49 publications

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Applications of Manganese-Enhanced Magnetic Resonance Imaging in Ophthalmology and Visual Neuroscience

A hierarchy of manganese competition and entry in organotypic hippocampal slice cultures

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