In vivo manganese-enhanced MRI for visuotopic brain mapping

Abstract

This study explored the feasibility of localized manganese-enhanced MRI (MEMRI) via 3 different routes of Mn(2+) administrations for visuotopic brain mapping of retinal, callosal, cortico-subcortical, transsynaptic and horizontal connections in normal adult rats. Upon fractionated intravitreal Mn(2+) injection, Mn enhancements were observed in the contralateral superior colliculus (SC) and lateral geniculate nucleus (LGN) by 45-60% at 1-3 days after initial Mn(2+) injection and in the contralateral primary visual cortex (V1) by about 10% at 2-3 days after initial Mn(2+) injection. Direct, single-dose Mn(2+) injection to the LGN resulted in Mn enhancement by 13-21% in V1 and 8-11% in SC of the ipsilateral hemisphere at 8 to 24 hours after Mn(2+) administration. Intracortical, single-dose Mn(2+) injection to the visual cortex resulted in Mn enhancement by 53-65% in ipsilateral LGN, 15-26% in ipsilateral SC, 32-34% in the splenium of corpus callosum and 17-25% in contralateral V1/V2 transition zone at 8 to 24 hours after Mn(2+) administration. Notably, some patchy patterns were apparent near the V1/V2 border of the contralateral hemisphere. Laminar-specific horizontal cortical connections were also observed in the ipsilateral hemisphere. The current results demonstrated the sensitivity of MEMRI for assessing the neuroarchitecture of the visual brains in vivo without depth-limitation, and may possess great potentials for studying the basic neural components and connections in the visual system longitudinally during development, plasticity, pharmacological interventions and genetic modifications.

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

“…They partially transected the optic nerve near the optic head to show retinotopic attenuation of signal in the superior colliculus. Later studies further expanded the connectivity work previously performed, using varied injection techniques (intravitreal, intracortical, subcortical) to provide more detailed descriptions of the connections between parts of the visual system (Chan and Wu, 2012).…”

“…Subsequent research by Chan et al (2011b, 2014) and Chan and Wu (2012) expanded these previous studies to assess neuroarchitecture and functional relationships in the rat visual system using a variety of manganese injection techniques. They first investigated visual system development and found faster axonal transport of manganese in the developing rats, attributed to higher permeability of the blood-ocular and blood-brain barriers in the immature rat (Chan et al, 2011a).…”

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

“…Mn 2+ is a Ca 2+ analog that is absorbed by excitable cells through voltage-gated calcium channels [particularly L-type Ca v 1.2 channels (6)], Na + -Ca 2+ exchangers on the cell membrane (7-10) in addition to other routes of Na + /Mg 2+ antiporters, transferrin and divalent metal transporter-1 (DMT1) (11)(12)(13). At present, MEMRI is mainly used in three areas: studies of anatomy and cellular structure (14)(15)(16)(17)(18), tracing of neural connections (5,19,20), and brain function (21)(22)(23)(24)(25)(26). After entering into cells, Mn 2+ is transported along neurons via microtubule-dependent axonal transport and reaches secondary neurons by transport across synapses, thereby enabling anterograde tracing of associated neural pathways (27)(28)(29).…”

Manganese‐enhanced MR imaging (MEMRI) combined with electrophysiology in the study of cross‐modal plasticity in binocularly blind rats

“…Manganese ion (Mn 2+ ) is a paramagnetic contrast agent and a calcium analog for MRI, which prompts its application as a preferred contrast agent to trace the neural pathway (Pautler et al, 1998). Recently, several investigators have applied manganese‐enhanced MR imaging (MEMRI) to explore visual pathways in living animals, as well as brain plasticity or reorganization after stroke, blindness and nerve injury, revealing that MEMRI could be a promising method to study the injury and reorganization in neuronal connections (Berkowitz et al, 2006; Chan et al, 2011a,b, 2012, 2014, 2008; Chan and Wu, 2012; Cross et al, 2006; Haenold et al, 2012; Lee et al, 2007; Pautler et al, 1998; Thuen et al, 2005; Van der Linden et al, 2004; van der Zijden et al, 2008; Watanabe et al, 2001). Nevertheless, these studies only focus on the changes of visual pathway but pay little attention on the generation of nerve fiber connections between the visual and auditory pathways after binocular blindness (visual to auditory cross‐modal plasticity).…”