Yuki Mori^1,2, Ting Chen^1,2, and Yoshichika Yoshioka^1,2
1Biofunctional Imaging, Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan, ²Center for Information and Neural Networks, Suita, Osaka, Japan

Combination of MRI and nanoparticles has a possibility for visualizing the dynamics of cells in mouse brain and previously we reported the time-lapse movie analysis have a good feasibility to track the single-cell migration in mouse brain. In this study, we improve the temporal resolution of time-lapse MRI movie with SPIO-based in-situ cell labeling and assess the difference of velocity and direction of immune cell migration between the healthy brain and ischemic-injured brain. We showed that time-lapse MRI has a good possibility to track the cell migration and assess the difference of cell kinetics between normal and ischemic lesion.

Jeff M Gaudet^1,2, Matthew S Fox¹, Amanda M Hamilton¹, and Paula J Foster^1,2
1Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada, ²Medical Biophysics, Western University, London, Ontario, Canada

Mesenchymal Stem Cells (MSC) are currently being investigated as a candidate for clinical trials. In this study we investigate a novel technique for imaging both the implanted stem cells, along with the inflammatory response in vivo using dual iron/fluorine MRI agents. MSC were labeled in vitro with ¹⁹F prior to implantation and phagocytic immune cells were labeled in situ with intravenous (IV) iron. Quantification of ¹⁹F-MRI on day 0 agrees with the expected number of cells. Following IV administration of iron, signal voids were observed at the site of implantation in the proton images and the ¹⁹F signal drops significantly.

Sayuan Liang¹, Yipeng Liu², Tom Dresselaers¹, Karim Louchami³, Sabine Van Huffel², and Uwe Himmelreich^1
1Department of Imaging & Pathology, KU Leuven, Leuven, Flemish Brabant, Belgium, ²ESAT, KU Leuven, Leuven, Flemish Brabant, Belgium, ³Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium

In this study, different compressed sensing algorithms were implemented and applied for low SNR 19F application: in particular imaging of transplanted pancreatic islets with PFCE labeled. We demonstrated that by using compressed sensing technique, the SNR/t could be improved by factor of 3-4. Among different algorithms, two-level method is considered the fastest one with relative good accuracy.

Jinjin Zhang¹, Hattie L. Ring^1,2, Katie Hurley², Qi Shao³, Nathan D. Klein², Christy Haynes², John Bischof⁴, and Michael Garwood^1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Department of Chemistry, University of Minnesota, MN, United States, ³Department of Biomedical Engineering, University of Minnesota, MN, United States, ⁴Department of Mechanical Engineering, University of Minnesota, MN, United States

The positive contrast due to T1-shortening from SPIO nanoparticles created by SWIFT sequence was applied to quantify in-vivo biodistribution of SPIONs in major organs of mouse at concentrations up to 2 mg Fe/ml (=35 mM), which is more than one order of magnitude higher than was previously reported. SPIONs were delivered intravenously. The average R1 of liver and kidney post-injection both showed linear dependence on the iron concentration in corresponding organ measured by ICP-MS. SWIFT T1 mapping is a promising tool to assess SPIONs uptake, biodistribution and clearance processes in major organs for nanoparticle-based thermal therapy or drug delivery systems.

Patricia Pais Roldán¹, Ajeet Singh¹, Hellmut Merkle¹, Hildegard Schulz¹, and Xin Yu^1
1Max Planck Institute, Tuebingen, Baden-Wuerttemberg, Germany

Here we described the impact of the high magnetic field (MF) on zebrafish larvae aiming to identify potential biological MR sensors. 14T-MF exposures longer than 2 hours in zebrafish larvae led to fusion of 2 otoliths (CaCO3 crystals in the inner ear responsible for balance and hearing) and a subsequent aberrant balance behavior, a phenotype already described in genetic mutants. Identification of the cellular and molecular mechanisms underlying this MF-induced otolith-fusion may be tackled with a zebrafish mutagenesis approach and might contribute in an efficient way to search for MR sensors in biological models.

Marianne Boucher¹, Nicolas Ginet², Françoise Geffroy¹, Sandra Préveral², Géraldine Adryanczyk-Perrier², Michel Pean², Christopher T Lefèvre², Daniel Garcia², David Pignol², and Sébastien Mériaux^1
1UNIRS, CEA/DSV/I2BM/NeuroSpin, Saclay, France, ²LBC, CEA/DSV/IBEB/SBVME, Saint-Paul-lez-Durance, France

Magnetosomes are iron nanocrystals embedded in a lipid bilayer which are produced by magnetotactic bacteria. We propose to demonstrate the efficiency of magnetosomes as T₂ contrast agent for MRI, and the feasibility of harvesting functionalized magnetosomes from genetically modified bacteria. RGD peptide, known for targeting α_νβ₃ integrins, has been chosen for functionalization and the affinity of targeting magnetosomes is demonstrated with U87 cells. The contrasting properties of magnetosomes are assessed by acquiring T₂*w images prior and after injection and comparing number of detected hypointense voxels. Thus, magnetosomes possess MRI sensitivity and α_νβ₃ specificity required for future molecular imaging experiments.

Leon C. Ho^1,2, Bo Wang^3,4, Ian P. Conner^3,4, Yolandi van der Merwe^1,4, Richard A. Bilonick³, Ed X. Wu², Seong-Gi Kim^1,5, Gadi Wollstein³, Joel S. Schuman^3,4, and Kevin C. Chan^1,3
1Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China, ³Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁴Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea

Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. To date, the spatiotemporal patterns of neurodegeneration in the visual system and the relationships with excitotoxic retinal injury and optic neuropathy are not fully elucidated. In this study, we employed DTI and MEMRI to study the microstructural alterations, anterograde Mn transport and their correlations along the visual pathway upon N-methyl-D-aspartate (NMDA)-induced glutamate excitotoxicity in the eye, in order to determine the pathophysiological events and structural-physiological relationships in the injured visual pathways.

Anna Ulyanova¹, Judy Chia Ghee Sng², Weiping Han³, and Kai-Hsiang Chuang^1
1Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, Singapore, ²Department of Pharmacology, National University of Singapore, Singapore, Singapore, Singapore, ³Lab of metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, Singapore

Manganese-Enhanced MRI (MEMRI) has been used to detect brain connectivity and activity in vivo. MEMRI signal depends on various factors affecting Mn2+ uptake and transport. To what extent MEMRI can reflect neuronal activity is still uncertain. We evaluated whether MEMRI signal in different hypothalamic nuclei represents Ca2+ activity by Ca2+ channel blockade, axonal transport by microtubule disruption, and neural activity by c-Fos expression. We have confirmed MEMRI can be used for mapping certain but not all activated neuronal pathway in hypothalamus. These findings can facilitate the interpretation of hypothalamic neurocircuit network in responding to nutritional and hormonal signals using MEMRI.

Galit Saar¹, Corina M. Millo², Lawrence P. Szajek², Jeff Bacon², Peter Herscovitch², and Alan P. Koretsky^1
1LFMI/NINDS, NIH, Bethesda, MD, United States, ²PET Department, Clinical Center, NIH, Bethesda, MD, United States

Manganese has been used as a functional contrast agent in many pre-clinical MRI studies. However, Mn²⁺ cellular toxicity limits its use as contrast agent in humans to low concentrations. We studied ⁵¹Mn (t1/2=46.2min) and ⁵²Mn (t1/2=5.6days) for PET imaging in rats and monkeys. We show that manganese radiotracers give similar contrast to Mn²⁺ in MRI with accumulation in different tissues following systemic infusion even at the low concentration used. ⁵²Mn-PET can trace olfactory pathways in the brain following intranasal administration in monkey, similar to MEMRI in rodents. Manganese PET should allow using the unique properties of Mn in clinical studies.

Rebecca M Schur¹, Li Sheng¹, Bhubanananda Sahu², Guanping Yu¹, Song-Qi Gao³, Xin Yu¹, Akiko Maeda², Krzysztof Palczewski³, and Zheng-Rong Lu^1
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Ophthamology and Visual Sciences, Case Western Reserve University, Cleveland, OH, United States, ³Pharmacology, Case Western Reserve University, Cleveland, OH, United States

Numerous therapies to treat degenerative retinal diseases are currently in preclinical development. To evaluate therapeutic efficacy of these drugs, a manganese-enhanced MRI (MEMRI) protocol was implemented to simultaneously evaluate both structure and function of retinas of treated mice. Following intravitreous injection of MnCl2, signal enhancement was measured in the retinas of healthy and treated animals, while in light-induced blinded animals, signal in the retina remained unchanged. Results were consistent with standard OCT, histology, and ERG methods. This work suggests that MEMRI is a promising alternative technique to evaluate therapeutic efficacy of retinopathy drugs during preclinical development.