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

Abstract

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.

Transient Hypothyroidism During Lactation Alters the Development of the Corpus Callosum in Rats. An in vivo Magnetic Resonance Image and Electron Microscopy Study

“…As already discussed in the case of the anterior commissure ( Lucia et al, 2018 ), this raises the important issue in MRI analysis of differentiation between delayed myelination and hypomyelination ( van der Knaap and Wolf, 2010 ) in infants and children suffering diseases affecting white matter development. Enhanced approaches such as MRI through Mn 2+ injection (MEMRI; Chan et al, 2012 ; Deng et al, 2019 ) and diffusion kurtosis image (DKI; Cheung et al, 2009 ) which is highly sensitive and directionally specific, should add valuable information to the study of developmental ultrastructural changes in white matter and the plasticity of callosal connections in normal and hypothyroid rats.…”

Non-invasive radionuclide imaging of trace metal trafficking in health and disease: “PET metallomics”

“… 72 The use of MEMRI in neuroscience has been reviewed. 73 The large quantities of manganese that must be administered for adequate MR contrast, which are greatly in excess of those found biologically, unavoidably perturb homeostasis of manganese and probably other trace metals, and may be toxic. MEMRI is unlikely, therefore, to provide a clinically useful or indeed realistic summary of normal manganese handling in vivo .…”

Role of Structural, Metabolic, and Functional MRI in Monitoring Visual System Impairment and Recovery

“…Although chelated manganese (eg, Mn-DPDP) has been used in clinical imaging of the pancreas, ophthalmological use of manganeseenhanced MRI is primarily limited to animal studies due to toxicity concerns. 15 Diffusion MRI Diffusion imaging provides information on a microstructural scale by measuring the average displacement of molecules within a voxel of tissue. Two common types are diffusionweighted imaging (DWI), which measures water diffusivity in a single direction and offers the basic building blocks for more advanced diffusion models; and diffusion-tensor imaging (DTI), a method that primarily exploits anisotropic diffusion in the microscopic environment along multiple directions within a voxel.…”