Bryan H DeLaGarza¹, Guang Li¹, Yen-Yu I Shih¹, and Timothy Q Duong^1
1Research Imaging Institute, Ophthalmology/Radiology, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, United States

This study used functional manganese-enhanced MRI (MEMRI at 20x20µm) to study the retina under light and dark adaptation. Layer-specific MEMRI of the inner retina, outer retina and the choroid were resolved and they were assigned with independent confirmation of the bounding vascular layers via an intravascular contrast agent. The outer retina had lower MEMRI activity in light compared to dark adaption. The inner retina had higher MEMRI activity in light compared to dark adaption. The choroid MEMRI activity was not statistically different between light and dark adaptation. This approach could have potential applications to probe retinal dysfunction in diseased states.

Kevin C Chan^1,2, and Ed X. Wu^1,3
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong, China, ²Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ³Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China

This study employed localized Mn-enhanced MRI via 3 different routes of Mn2+ administrations for visuotopic brain mapping of retinal, callosal and transsynaptic connections in the normal and reorganized rat brains. In normal brains, fractionated intravitreal Mn2+ injection resulted in Mn enhancements in the contralateral superior colliculus (SC) and lateral geniculate nucleus (LGN) by 45-60% at 1-3 days after initial Mn2+ injection, and in the contralateral primary visual cortex (V1) by about 10% at 2-3 days after initial Mn2+ injection. Direct, single-dose Mn2+ injection to the LGN resulted in Mn enhancement by 8-11% in SC, and 13-21% in V1 of the ipsilateral hemisphere at 8 to 24 hours after Mn2+ administration. Intracortical, single-dose Mn2+ injection to the visual cortex resulted in Mn enhancement by 15-26% in ipsilateral SC, 53-65% in ipsilateral LGN, 17-25% in contralateral V1/V2 transition zone, and 32-34% in the splenium of corpus callosum at 8 to 24 hours after Mn2+ administration. Notably, some patchy patterns were apparent near the V1/V2 border of the contralateral hemisphere. Upon intracortical Mn injection, animals which had undergone neonatal binocular enucleation exhibited larger projection volumes by about 74% near the V1/V2 border of the contralateral hemisphere compared to normal rat brains at 3 months old. 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 in the visual system longitudinally during development, plasticity, therapeutic interventions and genetic modifications.

Tsen-Hsuan Lin¹, and Sheng-Kwei Song^2
1Physics, WUSTL, St Louis, MO, United States, ²Radiology, Washington University in St Louis, St Louis, MO, United States

Manganese enhanced MRI (MEMRI) with topical loading is a novel approach to investigate anterograde axonal transport of the visual pathway. There is no need to perform intraocular injection physically damaging the eye. Topical loading has been demonstrated to produce similar MEMRI results as with intraocular injections. However, it is still uncertain if visual function is affected after MnCl₂ loading. This study determined the minimum dosage for the success MEMRI and measured the visual function after MnCl₂ loading. Mouse vision was affected but slowly recovered with 0.75M MnCl₂ loading. Based on DTI parameters of optic nerve and T2W images of retina, the injured retina is likely the cause of the impaired visual function.

Ileana Ozana Jelescu¹, Romuald Nargeot², Denis Le Bihan¹, and Luisa Ciobanu^1
1NeuroSpin, CEA/DSV/I2BM, Gif sur Yvette, France, ²Université Bordeaux 1, CNRS UMR 5287, Bordeaux, France

Manganese is increasingly used as a neuronal tract tracer but its exact transport pathways are yet to be identified. Aplysia californica provides an ideal framework of identified and large neurons to explore this matter. We performed MEMRI on its buccal ganglia to study the Mn²⁺ transport in resting state and following dopamine (DA)-induced activation. We confirmed, for the first time using MEMRI, the known axonal projections of identified motor neurons in the peripheral nerves of the ganglia. Images following DA perfusion showed intercellular Mn²⁺ transport with activation. The synapses involved are to be confirmed by ongoing experiments.

Alexia Daoust^1,2, Emmanuel Luc Barbier^1,2, Annie Andrieux^1,2, Sylvain Bohic^1,3, and Jean-Christophe Deloulme^1,2
1INSERM, U836, Grenoble, France, ²Université Joseph Fourier, Grenoble Institut des Neurosciences, Grenoble, France, ³European Synchrotron Radiation Facility, Grenoble, France

Stable tubule only polypeptide deficient mice (STOP KO) are devoid of cold stable microtubule, which induces a synaptic deficit. In this study, we evaluate the cortical projections in these mice and in the corresponding wild type: functionally, using MEMRI (between 2 and 24h after intracortical injections) and structurally using gold staining histology. We observed that the functional deficits observed (long-range projections) are not correlated to structural deficit (reduction in tract size).

Martin Freitag¹, Nadja Walder², Jens Hartmann², Heinz Redl², Peter Parzer³, and Bram Stieltjes^1
1Quantitative Image-based Disease Characterization, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany, ²Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Research Center of the AUVA, Vienna, Austria, ³Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, Section Disorders of Personality Development, Heidelberg, Germany

The purpose of this study was to evaluate the short-term therapeutic effect of recombinant Erythropoietin therapy in rats with spinal cord injury (SCI) using physical assessment and manganese enhanced magnetic resonance imaging (MEMRI). Both the physical performance and the manganese uptake improved significantly in the treated group compared to untreated controls. Therefore, we conclude that MEMRI is well suited for the evaluation of EPO induced therapy effects in SCI and that MEMRI may be suitable for future in vivo longitudinal therapy studies.

Susann Boretius^1,2, Tanja Ducic³, Angelika Escher⁴, Christine Stadelmann⁴, and Jens Frahm^1
1Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany, ²Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany, ³Hasylab, DESY, Hamburg, Germany, ⁴Institute of Neuropathology, University Medical Center, Georg-August-University, Göttingen, Germany

Due to its calcium-like properties and shortening of T1, manganese is widely used in experimental animal research. However, little is known about Mn²⁺ accumulation under pathological conditions. We analyzed C57BL/6 mice at 2 and 4 weeks after cuprizone treatment resulting in toxic demyelination and at 10 days after cuprizone withdrawal (recovery stage). At each time manganese accumulation was observed in distinct brain areas, correlating best with activated microglia cells. Synchroton based X-ray fluorescence microscopy revealed co-localization of calcium and manganese in cell-body like structures. Manganese-enhanced MRI may significantly contribute to understanding of immune cell activation and accumulation in various diseases.

Neeraj Rastogi¹, Nidhi Tyagi², Kaushik Ghosh², and Raja Roy^1
1Centre of Biomedical Magnetic Resonance, Lucknow, Uttar Pradesh, India, ²Department of Chemistry, Indian Institute of Technology, Roorkee, Uttarakhand, India

In the present work, a non-lanthanide Manganese containing new ligand based MRI contrast agent has been designed and synthesized with a possibility of binding with amyloid plaques. Relaxivity studies were performed at 3T under different imaging parameters. The contrast agent demonstrated comparable r1with standard as well as enhanced negative contrast in relaxivity studies performed on phantom created. The relaxivity value r1 for Mn contrast was found to be comparable (7.24 /mM/s) with respect to Gd-DTPA (8.26 /mM/s). While, T2 shortening efficacy in terms of r2 was 41.26 /mM/s approximately four times more (11.10 /mM/s) as compared to Gd-DTPA.

Ya Chen¹, Akemichi Baba², Toshio Matsuda², and Xin Yu^1
1Department of Biomedical Engineering and Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, United States, ²Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

The present study aimed at investigating whether manganese-enhanced MRI (MEMRI) is also sensitive to detect the calcium channel and NCX activities after ischemia during earlier reperfusion. Using a rapid T1-mapping method, we investigated the dynamics of R1 changes in manganese-perfused rat hearts with and without 20 min ischemia and with and without NCX inhibition by SEA0400.

Dai Shan¹, Shaorui Li¹, Liqin Yang², and Hao Lei^1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, ²Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, China

In this study we proposed a protocol to analyze high resolution MEMRI data with a voxel-based approach. The aim is to build a high resolution MEMRI atlas which can be used to reveal fine cytoarchitecture of the brain at the group level, and to identify functionally distinct brain regions which show differential activities in Mn2+ uptake/deposition.