Manganese Enhanced MRI: Methods & Applications
Monday 20 April 2009
Room 310 16:30-18:30


Tom C.C. Hu and Robia Pautler

16:30  150. Voxel Based Morphometric Analysis of the Gbx2 Mutant Mouse Phenotype via MEMRI
    Kamila Urszula Szulc1,2, Brian J. Nieman1,2, Roy V. Sillitoe3, Alex L. Joyner3, Daniel H. Turnbull1,2
1Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY, USA; 2Radiology, NYU School of Medicine, New York, NY, USA; 3Developmental Biology, Sloan-Kettering Institute, NY, New York, NY, USA
    The cerebellum (Cb) is a highly patterned brain structure with a stereotypical foliation pattern playing an essential role in normal motor and cognitive function. Previously we demonstrated the feasibility of in vivo longitudinal MEMRI of Cb development in normal and Gbx2-CKO mice during critical neonatal stages of foliation, including volumetric analysis of the vermis deletion and abnormalities in the flocculus-paraflocculus complex and deep cerebellar nuclei that were not previously reported. In the current study, we extended our analysis to whole brain deformation-based morphometry in order to provide a comprehensive, unbiased characterization of the Gbx2-CKO phenotype.
16:42 151. Myelin Mapping in Living Mice Using Magnetization Transfer and Manganese
    Takashi Watanabe1, Jens Frahm1, Thomas Michaelis1
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany
    This work demonstrates for the first time the use of manganese for mapping myelin-rich structures in the brain of living mice in magnetization-transfer weighted MRI (3D FLASH). The contrast between myelin-rich structures and background was improved after manganese injection. A reduced saturation of mobile protons was pronouncedly seen in the water-rich background, while the marked saturation in myelin-rich structures through magnetization transfer from the large pool of bound protons was less affected. Administration of hydrophilic T1-shortening agents to neural tissue fluid in vivo increases the signal intensity of the brain advantageously for a magnetization-transfer based mapping of myelin-rich structures.
16:54 152. Changes in Callosal and Thalamic Connectivity Following Peripheral Nerve Damage to the Rodent Forepaw Detected with Manganese Enhanced MRI
    Jason Tucciarone1, Galit Pelled1, Alan Koretsky1
National Institutes of Health, Bethesda, MD , USA

The purpose of this work was to determine if MEMRI neural tracing could detect changes in the laminar functional architecture of cortical-cortical and thalamo-cortical somatosensory pathways following complete nerve deafferentation of the rat forepaw. Previously it has been demonstrated that cortical reorganization observed following complete peripheral nerve injury affects functional MRI responses both in healthy and deprived cortices. Reduced manganese transport was found in lamina 3 of the deprived cortex after injection of manganese to the healthy cortex predicting that input into this layer has decreased. Second, increases in T1 enhancement in the healthy cortex were found after injecting manganese into the healthy thalamus. There was increased tracing throughout the cortex which was highest at the lamina 3/4 interface. Thus, both cortical-cortical and thalamic-cortical neuronal pathways are affected by the injury, and contribute to the deprived somatosensory reorganization.

17:06 153.

A Novel Method for Dynamic Manganese-Enhanced MRI


Hanbing Lu1, Steven Demny1, William Rea1, Yantao Zuo1, Yihong Yang1, Elliot A. Stein1
National Institute on Drug Abuse, NIH, Baltimore, MD, USA

    ME-MRI has been successfully applied to map neuronal response to a variety of stimuli. However, manganese has very low permeability through the blood-brain barrier(BBB). For studies employing pharmacological or other manipulations, where multiple cortical and subcortical structures are expected to be activated, temporal disruption of BBB appears to be necessary for whole brain imaging. A novel method using an agent that normally targets endothelial barrier antigen to open BBB for dynamic ME-MRI experiments is presented. This agent is infused intravenously, avoiding surgical trauma associated with carotid artery catheterization when hyperosmolar mannitol is used to open BBB.
17:18  154. In Vivo Tracing of Cortical Laminar Structure in the Rodent Olfactory System Using Manganese-Enhanced MRI (MEMRI)
    Der-Yow Chen1, Kai-Hsiang Chuang2, Stephen Dodd1, Alan Koretsky1
NINDS, National Institutes of Health, Bethesda, MD, USA; 2Singapore Bioimaging Consortium, Singapore
    MEMRI can be used for neuronal tracing in the olfactory pathway. Here it is demonstrated that MEMRI visualizes the laminar structure of the olfactory system and traces layer-specific inputs to olfactory cortices. MnCl2 was infused into nostrils of rats which were imaged at several time points. Layers and boundaries of olfactory cortices were evident 48 h after infusion. Mn2+ enhancement in the superficial layer was observed earlier than the deep cell layer, consistent with known connections. Therefore, MEMRI neural tracing is specific at the level of cortical layers in the olfactory pathway, consistent with previous measurements of the somatosensory pathway.
17:30 155.

Manganese Tract Tracing in Zebrafish

    Miriam Scadeng1, David Julian Dubowitz1, Nathan Gray1, Ellen Breen2
Radiology, University of California San Diego, La Jolla, CA, USA; 2Medicine, University of California San Diego, San Diego, CA, USA
    The use of MEMRI to study neural networks and cardiac function has rapidly expanded in recent years. Zebrafish are rapidly emerging as a major new animal model for animal research as they have many unique qualities such as the ability to regenerate neuronal and cardiac tissues. The ability to perform in vivo MEMRI studies in zebrafish introduces this animal model to new areas of research.
17:42 156. Manganese-Enhanced MRI and 1H MR  Spectroscopy of the Hypothalamus in a Model of Dehydration Induced Anorexic Rats
    Nathalie Just1,2, Rolf Gruetter1,2
LIFMET, CIBM, EPFL, Lausanne, Switzerland; 2Department of Radiology, UNIL and HUG, Lausanne and Geneva, Switzerland
    The hypothalamus is responsible for metabolic processes of the Autonomic Nervous System. The ventromedial nucleus of the hypothalamus is responsible for the control of food intake. The use of manganese-enhanced MRI (MEMRI) to assess the neuronal circuitry involved in both autonomic and somatosensory pathways showed promises. In the present study, hypothalamic activation was performed by dehydration induced anorexia(DIA) in female rats. Enhancement of paraventricular nuclei following manganese injection coupled to metabolite concentration changes measured by 1H MR spectroscopy at 14.1T in DIA rats suggest that neuronal and metabolic analysis of the hypothalamus during activation are possible using MR methods.


17:54 157. MEMRI Study of Neonatal Hypoxic-Ischemic Injury in the Late Stage
    Iris Yuwen Zhou1,2, Kevin C. Chan1,2, Abby Y. Ding1,2, Edward S. Hui1,2, Ke Xia Cai1,2, Ed X. Wu1,2
Laboratory of Biomedical and Signal Processing, The University of Hong Kong, Hong Kong SAR, China; 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China
    In this study, in vivo MEMRI was employed to investigate the hypoxic-ischemic injury in the late phase. Mn2+ induced signal changes were examined using SPM coregistration and ROI analysis. T1WIs SI increase was detected in the perilesional region 24 hours after Mn2+ administration and it colocalized with the increase in glial cell density in GFAP staining, demonstrating the existence of reactive gliosis in the late phase after H-I injury.


18:06 158. Using Magnanese-Enhanced MRI to Monitor the Efficacy of Angiotensin Converting Enzyme Inhibitor Treatment in a Murine Myocardial Infarction
    Collier Gladin1, Lynsa Nguyen1, Christopher Middleton1, Jimei Liu1, Nathan Yanasak1, Tom C.-C. Hu1
Small Animal Imaging, Medical College of Georgia, Augusta, GA, USA
    There is a critical, yet unexplored, niche for using a non-invasive in vivo imaging technique to compare pharmaceutical treatment and assess the diagnostic improvement of ischemic tissue following myocardial infarction. This study demonstrates the ability of MEMRI to quantify the efficacy of an ACEi following myocardial infarction by segmenting and analyzing areas in and surrounding the ischemic site. This information potentially can be used to determine best used methods of clinical treatment following a cardiac event.


18:18 159. MRI Monitored Uptake of Manganese in the Mouse During Continuous Administration Using Osmotic Infusion Pumps
    Maria Rosario Sepulveda1, Tom Dresselaers2, Uwe Himmelreich2, Frank Wuytack1
Laboratory of Ca2+-transport ATPases, Department of Molecular Cell Biology, K.U.Leuven, Faculty of Medicine, Leuven, Belgium; 2Biomedical NMR-unit  / MoSAIC, K.U.Leuven, Faculty of Medicine, Leuven, Belgium

NeuroMRI studies using manganese as a paramagnetic contrast agent are often limited by the neurotoxicity of Mn2+. Fractionated injections can reduce the toxicity; however, we hypotisezed that a constant administration at very low doses will reduce toxicity even more without affecting the T1-weighted contrast. For this purpose we evaluated the T1 changes observed by implanting subcutaneously a mini-osmotic infusion pump loaded with MnCl2 in mice. This administration route simulates better the chronic exposure reported in some patients. Evaluation of temporal changes in contrast allow monitoring of uptake and clearance in the brain and several glands.