ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Scientific Session • Cell Memories: Cell Tracking & MEMRI

Wednesday 3 June 2015

Room 701 B

16:00 - 18:00


Ichio Aoki, Ph.D., Paula J. Foster, Ph.D.

16:00 0691.   In vivo monitoring of immune cell kinetics with time-lapse MRI in the ischemic lesion of mouse brain
Yuki Mori1,2, Ting Chen1,2, and Yoshichika Yoshioka1,2
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.

16:12 0692.   
Dual Iron/Fluorine Cell Tracking: Monitoring the Fate of Human Stem Cells and the ensuing Cellular Inflammatory Response
Jeff M Gaudet1,2, Matthew S Fox1, Amanda M Hamilton1, and Paula J Foster1,2
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.

16:24 0693.   
Comparison of different compressed sensing algorithms for low SNR 19F application --- imaging of transplanted pancreatic islets with PFCE labeled
Sayuan Liang1, Yipeng Liu2, Tom Dresselaers1, Karim Louchami3, Sabine Van Huffel2, and Uwe Himmelreich1
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.

16:36 0694.   Using SWIFT T1 mapping to quantify iron oxide nanoparticles uptake and biodistribution in organs in-vivo
Jinjin Zhang1, Hattie L. Ring1,2, Katie Hurley2, Qi Shao3, Nathan D. Klein2, Christy Haynes2, John Bischof4, and Michael Garwood1
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.

16:48 0695.   Sensing the high magnetic field: Fusion of otoliths in zebrafish larvae entails a hint
Patricia Pais Roldán1, Ajeet Singh1, Hellmut Merkle1, Hildegard Schulz1, and Xin Yu1
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.

17:00 0696.   Genetically functionalized magnetosomes as MRI contrast agent suitable for molecular imaging
Marianne Boucher1, Nicolas Ginet2, Françoise Geffroy1, Sandra Préveral2, Géraldine Adryanczyk-Perrier2, Michel Pean2, Christopher T Lefèvre2, Daniel Garcia2, David Pignol2, and Sébastien Mériaux1
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 ανβ3 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 ανβ3 specificity required for future molecular imaging experiments.

17:12 0697.   
Structural-Physiological Relationships in the Visual System upon Glutamate Excitotoxicity in the Eye using Diffusion Tensor Imaging and Manganese-enhanced MRI
Leon C. Ho1,2, Bo Wang3,4, Ian P. Conner3,4, Yolandi van der Merwe1,4, Richard A. Bilonick3, Ed X. Wu2, Seong-Gi Kim1,5, Gadi Wollstein3, Joel S. Schuman3,4, and Kevin C. Chan1,3
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.

17:24 0698.   
MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit.
Anna Ulyanova1, Judy Chia Ghee Sng2, Weiping Han3, and Kai-Hsiang Chuang1
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.

17:36 0699.   Manganese PET enables the same contrast as Manganese Enhanced MRI
Galit Saar1, Corina M. Millo2, Lawrence P. Szajek2, Jeff Bacon2, Peter Herscovitch2, and Alan P. Koretsky1
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.

17:48 0700.   Manganese-Enhanced MRI for Preclinical Evaluation of Therapeutic Efficacy of Retinal Degeneration Treatment
Rebecca M Schur1, Li Sheng1, Bhubanananda Sahu2, Guanping Yu1, Song-Qi Gao3, Xin Yu1, Akiko Maeda2, Krzysztof Palczewski3, and Zheng-Rong Lu1
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.