Mapping of Cellular Layers in Mouse Brain and Spinal Cord Using Magnetization Transfer and Manganese
Takashi Watanabe¹, Jens Frahm¹, Thomas Michaelis^1
1Biomedizinische NMR Forschungs GmbH am MPI für Biophysikalische Chemie, Göttingen, Germany

This work demonstrates the complementary and combined use of magnetization transfer and manganese administration in T1-weighted MRI of the brain and spinal cord of living mice. The off-resonance irradiation effectively suppresses the signal intensity of the white matter, while the bright signals of dense cellular assemblies are much less affected. This differential effect well complements the contrast induced by manganese administration. Thus, magnetization transfer may distinguish neuron-rich tissue from adjacent myelin-rich tissue. Furthermore, quantitative evaluations indicate a higher sensitivity for manganese when combined with magnetization transfer.

In Vivo Manganese-Enhanced MRI of Retinotopic Mapping in Superior Colliculus
Kevin C. Chan^1,2, Jiang Li³, Iris Y. Zhou^1,2, Kwok-fai So³, Ed X. Wu^1,2
1Laboratory of Biomedical Imaging 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; ³Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China

This study explores the capability of high-resolution 3D Mn-enhanced MRI (MEMRI) for in vivo retinotopic mapping of the rat superior colliculus (SC) upon partial transection of the intraorbital optic nerve. Upon intravitreal Mn2+ injection into both eyes, all animals in Group 1 (n=8) exhibited significantly lower signal intensity in the lateral side of the left SC compared to the left medial SC and right control SC 1 week after superior optic nerve transection in the right eye. Partial transection at other regions of the optic nerve in Group 2 (n=7) led to hypointensity in other regions of the left SC. The results of this study demonstrated the feasibility of high-resolution MEMRI for in vivo, 3D mapping of retinotopic projections in the SC upon reduced anterograde axonal transport of Mn2+ ions at sites of partial transections in the anterior visual pathways. Future MEMRI studies are envisioned that measure the retinotopic changes in normal development, disease, plasticity and therapy in longitudinal studies.

In Vivo Evidence of Axonal Transport Perturbation in a Mouse Model of Tauopathy: A Track-Tracing Memri Study
Anne Bertrand^1,2, Minh D. Hoang², Dmitry Novikov², Susan Pun², Pavan Krishnamurthy¹, Hameetha Banu¹, Benjamin Winthrop Little², Einar M. Sigurdsson¹, Youssef Zaim Wadghiri^2
1Physiology and Neuroscience, NYU Medical Center, New York, NY, United States; ²Radiology, NYU Medical Center, New York, NY, United States

We report a track-tracing MEMRI in a mouse model of tauopathy (P301L line). We compared transgenic and wild-type animals at an early stage (6 month-old), using a long timeframe protocol (9 consecutive MR examinations for each mice) and a mathematical modelization of axonal transport using a drift-diffusion model. We show that P301L mice display significant differences in 2 parameters of axonal transport : the value of the peak of Mn, and the time of the peak of Mn. We also observed trends in drift velocity V, leakage rate λ and apparent speed of Mn transport that were smaller in TG mice that in WT. This provides the first in vivo evidence of axonal transport impairment assessed by MRI in a model of tauopathy.

Logan Graphical Analysis for Quantitative Evaluation of Calcium Channel Activity in the Pituitary Gland Using Manganese-Enhanced MRI (MEMRI)
Christoph Leuze^1,2, Ichio Aoki¹, Yuichi Kimura^1
1National Institute of Radiological Sciences, Chiba, Japan; ²Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Sachsen, Germany

Logan graphical analysis (LGA), common in PET for the quantitative analysis of neuroreceptors, was performed with MRI to investigate the influence of stimulants and inhibitors on the Calcium channel activity in animal brain tissue. In this study LGA is applied to data which was acquired by measuring the concentrations of Manganese (Mn) in tissue and blood over a certain period of time after Mn-injection. The Mn uptake between experiments was varied by the excitatory neurotransmitter Glutamate and the Calcium channel blocker Verapamil. The analysis successfully delivers information about the varying in- and outflow of Mn from blood to tissue.

MEMRI Monitoring of Manganese Release and Transport in the Rat Brain Following Convection-Enhanced Delivery (CED) of Manganese (III)-Transferrin
Christopher H. Sotak^1,2, Alan P. Koretsky^3
1Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, United States; ²Radiology, University of Massachusetts Medical School, Worcester, MA, United States; ³NINDS/LFMI, National Institutes of Health, Bethesda, MD, United States

Convection-enhanced delivery (CED) of manganese(III)-transferrin (Mn(III)-Tf) into the rat brain was used to investigate its properties as an in vivo MRI contrast agent.  The spatio-temporal evolution of MEMRI signal enhancement and calculated T1 relaxation times following Mn(III)-Tf infusion was comparable to that observed following CED of Mn2+ alone.  Furthermore, Mn2+ released following intrastriatal Mn(III)-Tf infusion was transported along the striatonigral pathway and the temporal dynamics were in excellent agreement with the neuronal tract tracing studies that employ Mn2+ alone.  The results of this study are consistent with the release and subsequent transport of Mn2+ following receptor-mediated endocytosis of Mn(III)-Tf.

Quantitative Multi-Parametric Assessment of a Radiation-Induced Encepholodysplasia CNS Model Using Magnetic Resonance Imaging
Shigeyoshi Saito^1,2, Kazuhiko Sawada³, Xue-Zhi Sun, Kai-Hsiang Chuang⁴, Tetsuya Suhara, Iwao Kanno, Ichio Aoki
¹Tohoku Univeristy, Sendai, Miyagi, Japan; ²National Institute of Radiological Sciences, Chiba, Japan; ³Tsukuba International University, Tsukuba, Ibaraki, Japan; ⁴Singapore Bioimaging Consortium, Singapore

Induced T₁, T₂^* and Phase Changes Following Manganese Systemic Administration at 14.1T
Rajika Maddage¹, José P. Marques^2,3, Rolf Gruetter^2,4
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne , Lausanne, Switzerland; ²Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ³Department of Radiology , University of Lausanne, Lausanne, Switzerland; ⁴Department of Radiology, University of Lausanne and Geneva, Switzerland

Manganese enhanced MRI studies have been increasingly used in animal neuroimaging thanks to its T₁ shortening properties and enhancement specificity. The aim of this study was to quantitatively evaluate at 14.1T the dynamic evolution of T₁, T₂^* in different regions of the rat brain during manganese systemic administration and to access its impact on phase imaging. Preliminary results show enhancement in the hippocampus and cortex in phase imaging making it a potential tool to trace Mn²⁺ enrichment.

Dynamics of Mn Transport in the Mesolimbic System Reveal Neural Projections from the Nucleus Accumbens in Vivo
Jessica A. M. Bastiaansen^1,2, Xiaowei Zhang¹, Davit Janvelyan¹, Scott E. Fraser¹, Russell E. Jacobs^1
1Biological Imaging Center, California Institute of Technology, Pasadena, CA, United States; ²CIBM, EPFL, Lausanne, Switzerland

The Nucleus Accumbens (NAc) plays a fundamental role in the neural reward circuit. Herein, we investigated the feasibility of MEMRI to map neural circuitry, activation and anatomy in the rodent reward system in vivo. Using MEMRI and SPM, we monitored Mn dynamics along the afferent and efferent projections from the NAc after a stereotaxic injection of MnCl. Spatiotemporal connectivity in the mesolimbic system was visualized in vivo, providing a paradigm for future studies on the neurophysiological basis of addiction using MEMRI.

Repeated T1 Mapping in Brain Following Clinical Dosage of Teslascan
Pål Erik Goa¹, Christian Brekken², Anders Thorstensen², Brage Høyem Amundsen², Asta Kristine Håberg^3
1Dept. of Medical Imaging, St. Olavs University Hospital, Trondheim, Norway; ²Dept. of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; ³Dept. of Neuromedicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

Whole-brain T1-mapping was performed before and 1 day, 4 days and 7 days after administration of clinical dosage of Teslascan in 8 healthy male volunteers. ROI was defined in Hippocampus, Caudate Nucleus and Corpus Callosum, and the T1 relaxation time at different timepoints after injection was compared to baseline values. Only in hippocampus at day 1 after injection was a statistically significant reduction in T1 observed. At later timepoints for the hippocampus, and for caudate nucleus in general only a trend towards reduced T1 was observed. For Corpus Callosum no T1 changes were observed.

The Dose Makes the Poison - Studying Toxicity in MEMRI Applications
Barbara Gruenecker¹, Sebastian Frank Kaltwasser¹, Yorick H. Peterse¹, Philipp G. Saemann¹, Mathias Schmidt¹, Carsten T. Wotjak¹, Michael Czisch^1
1Max Planck Institute for Psychiatry, Munich, Germany

Different fractionated manganese injections schemes for MEMRI applications have been applied to study their influence on the animals’ health and stress response and MRI signal intensity in the brain of the often used mouse strain C57BL/6N. 8 applications of 30 mg/kg MnCl2 injected at an interval of 24 hours (8x30/24) were found to produce least toxic side effects while simultaneously producing highest MRI intensity and contrast compared to 6 injections of 30 mg/kg (6x30/48) and 3 injections of 60 mg/kg applied injected with 48 hours intervals. This method may allow functional MRI in freely behaving animals exposed to prolonged paradigms.