In vivo visuotopic brain mapping with manganese-enhanced MRI and resting-state functional connectivity MRI

Abstract

The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies.

4D MEMRI atlas of neonatal FVB/N mouse brain development

“…Automated segmentation was also adapted to track small regions in the cerebellum, to address fundamental questions related to the process of cerebellar foliation. Given the growing use of MEMRI for small-animal anatomical (Gazdzinski et al, 2012; Qiu et al, 2013; Szulc et al, 2013), functional (Cacace et al, 2014; Chan et al, 2014; Yu et al, 2005) and molecular (Bartelle et al, 2013) neuroimaging, these results should provide important background data for future analyses of brain development on multiple levels, in both normal mice and a variety of mutants.…”

“…MEMRI has emerged as a unique and effective in vivo imaging approach for a variety of anatomical and functional studies in the mouse brain (Boretius and Frahm, 2011; Chan et al, 2014; Inoue et al, 2011; Koretsky and Silva, 2004; Nieman and Turnbull, 2010; Pautler, 2004, 2006; Silva et al, 2004; Watanabe et al, 2010; Yu et al, 2005). In the developing mouse brain, the increased SNR and contrast due to cellular uptake of paramagnetic Mn ions has made it possible to analyze brain sub-regions and perform morphological phenotype analysis from embryonic to early postnatal stages (Deans et al, 2008; Szulc et al, 2013; Wadghiri et al, 2004).…”

Magic Angle–Enhanced MRI of Fibrous Microstructures in Sclera and Cornea With and Without Intraocular Pressure Loading

“…Magnetic resonance imaging (MRI) allows noninvasive and longitudinal monitoring of ocular structures, such as the retina [8][9][10][11][12][13][14] and anterior and vitreous chambers, 15-17 without depth limitation. It has also been used to image the sclera and cornea and to obtain details of ocular anatomy such as ocular shape and tissue thickness.…”

Long-Term Effects of Neonatal Hypoxia-Ischemia on Structural and Physiological Integrity of the Eye and Visual Pathway by Multimodal MRI

“…As needle insertion and material injection in the eye might induce reactive changes in the retina and possibly the visual system, to address the potential issue of ''injection artifact,'' we also compared the current Cr-MRI and Mn-MRI data from the HI-injured animals with healthy control animals from our previous data using the same MRI acquisition parameters, the same Cr or Mn dose, and the same time points before and after Cr or Mn injection. 20,29 For Cr-MRI, no significant difference was observed between HI-injured animals and healthy animals on either side of the retina before Cr injection (unpaired t-tests, P > 0.05). One day after Cr injection, the Cr enhancement in the retina of the healthy animals was significantly stronger than the ipsilesional left retina (unpaired t-test, P < 0.05) but not contralesional right retina (unpaired t-test, P > 0.05) of the HI-injured animals.…”

“…14,15,[22][23][24] Local administration of potassium dichromate (K 2 Cr 2 O 7 ) and manganese chloride (MnCl 2 ) MR contrast agents may help assess the biochemical properties of the retina and the active axonal transport in the visual pathway. 17,18,20,[25][26][27][28][29] Diffusion tensor MR imaging (DTI) probes the anisotropic property of tissue water 30,31 and has been successfully used to reveal the microstructural integrity of the optic nerve and optic tract in normal, developing, and injured brains. [30][31][32][33][34][35] In this study, we tested the hypothesis that the structural and physiological effects of neonatal HI occur in both the eye and the brain's visual pathways and persist in the long term.…”