Poster Sessions 1038. In Vivo High-Resolution Magic Angle Spinning Proton MR Spectroscopy of Small Whole-Model Organism C. Elegans Valeria Righi 1,2 , Alex A. Soukas 3 , Gary Ruvkun 3 , A Aria Tzika 1,2 1 NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3 Department of Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States We demonstrate metabolic biomarker profiles with high-resolution magic angle spinning proton MR spectroscopy (HRMAS H1 MRS) of living Caenorhabditis elegans (C. elegans) worms. This work opens up perspectives for the use of H1 HRMAS-MRS as a metabolic profiling method for C. elegans. Because it is amenable to high throughput and is shown to be highly informative, this approach may lead to a functional and integrated metabolomic analytic approach of the small organism C. elegans, which has been used extensively in studies of aberrant metabolism, and should help in identifying, investigating, and even validating new pharmaceutical targets for metabolic diseases. 1039. Morphologic Abnormalities of Mucopolysaccharidosis Type VII Characterized by High Resolution MRI in a Mouse Model Ilya Michael Nasrallah 1 , Sungheon Kim 2 , Ranjit Ittyerah 1 , Stephen Pickup 1 , John H. Wolfe 3,4 , Harish Poptani 1 1 Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; 2 New York University; 3 Departments of Pathobiology and Pediatrics, University of Pennsylvania; 4 Children's Hospital of Philadelphia Mucopolysaccharidosis Type VII (MPS VII) is one of the degenerative lysosomal storage diseases characterized by intracellular vacuolization. Using highresolution MRI in a mouse model of MPS VII with manual segmentation, we identify decreases in corpus callosum and anterior commisure volume and slight increase in hippocampus volume in mutant mice. A decrease in corpus callosum volume thickness is confirmed at histology. These parameters could be used for monitoring experimental response to gene therapy treatments. 1040. MRI Phenotyping of Craniofacial Development in Transgenic Mice Embryos Hargun Sohi 1 , Seth Ruffins 1 , Yang Chai 2 , Scott Fraser 1 , Russell Jacobs 3 1 Caltech; 2 USC; 3 Caltech, Pasadena, CA, United States Microscopic MRI (μMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualizing abnormalities in craniofacial development. μMRI methods rely on reduction of the tissue T1 relaxation time by penetration of a gadolinium chelate contrast agent. The use of contrast agents is aimed at reducing the T1 relaxation time of the sample thus permitting a decrease in acquisition scan time, and/or increase in image signal-to-noise ratio (SNR), and/or increase in spatial resolution. In this work we apply these technologies to delineating changes in a murine cleft palate model system. 1041. Relaxivity Tissue Differentiation Among Gd-Based Contrast Agents in Ex-Vivo Mouse Embryo Imaging Michael David Wong 1 , X Josette Chen 1 , R Mark Henkelman 1 1 Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada The role of MRI in developmental biology, specifically in mouse embryo organogenesis and phenotyping, is significantly increasing due to technologies that allow for high image resolution and throughput. The majority of ex-vivo MRI mouse embryo studies improve image contrast and SNR by immersing the sample into some concentration of Gd-based contrast agent. It is widely believed that all gadolinium-based contrast agents have identical tissue interactions and provide similar MRI images despite the differences in Gd-chelates. Here, relaxivity (r1) variation amongst mouse embryo organs is observed for one class of contrast agents, while homogeneity is seen throughout the embryo for another. 1042. Contrast Enhancement in Preserved Zebra Finch Brains Utilizing Low Temperatures at High Magnetic Fields Parastou Foroutan 1,2 , Susanne L. T. Cappendijk 3 , Samuel C. Grant 1,2 1 Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States; 2 CIMAR, The National High Magnetic Field Laboratory, Tallahassee, FL, United States; 3 Biomedical Sciences, College of Medicine, The Florida State University, Tallahassee, FL, United States Temperature is evaluated as an easy method of increasing contrast in preserved tissue. In this study, excised, fixed brains from the adult male zebra finch were scanned at multiple temperatures between 5-25 Celsius. Relaxation (T1, T2 and T2*), signal-to-noise, relative contrast and contrast-to-noise were measured at each temperature. In addition, high-resolution 3D gradient recalled echo scans were acquired at 40-micron isotropic resolution at each temperature. Although all relaxation mechanisms displayed decreases with temperature, only T2* contrast displayed structural enhancement. The ramifications of these findings are discussed with respect to microimaging studies of preserved tissue samples. 1043. Phenotyping a Novel Mouse Model of Congenital Heart Disease Using μMRI Jon Orlando Cleary 1,2 , Francesca C. Norris 3,4 , Karen McCue 5 , Anthony N. Price 3 , Sarah Beddow 5 , Roger J. Ordidge 2,6 , Peter J. Scambler 5 , Mark F. Lythgoe 3 1 Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health , University College London, London, United Kingdom; 2 Department of Medical Physics and Bioengineering, University College London, London, United Kingdom; 3 Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health, University College London, London, United Kingdom; 4 Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX), University College London, London, United Kingdom; 5 Molecular Medicine Unit, UCL Institute of Child Health,
Poster Sessions University College London, London, United Kingdom; 6 Wellcome Trust Advanced MRI Laboratory, University College London, London, United Kingdom CHARGE and DiGeorge syndromes are conditions associated with haploinsufficiency of specific genes (CHD7 and TBX1) and are characterised by cardiovascular defects. Knockout mice are an important tool in genetic studies, allowing genes implicated in congenital defects to be identified and characterised. Micro-MRI is an emerging technique for high-resolution cardiac phenotyping, enabling the acquisition of 3D images of multiple embryo in a single scan. Given the phenotypic overlap of these conditions, we examined heart morphology in novel double-knockout mouse embryos (Chd7+/-Tbx1+/-), performing an assessment using MRI. In particular, we identified an increased incidence of ventricular septal defects in these mice. 1044. Optimised µMRI for Phenotyping the Tc1 Model of Down Syndrome Jon Orlando Cleary* 1,2 , Francesca C. Norris* 3,4 , Frances K. Wiseman 5 , Anthony N. Price 3 , ManKin Choy 3 , Victor L.J. Tybulewicz 6 , Roger J. Ordidge 2,7 , Elizabeth M.C. Fisher 5 , Mark F. Lythgoe 3 1 Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health , University College London, London, United Kingdom; 2 Department of Medical Physics and Bioengineering, University College London, London, United Kingdom; 3 Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health, University College London, London, United Kingdom; 4 Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX), University College London, London, United Kingdom; 5 Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, United Kingdom; 6 MRC National Insitiute for Health Research, London, United Kingdom; 7 Wellcome Trust Advanced MRI Laboratory, University College London, London, *equal contribution ‘Staining’ brain tissue with MR contrast agents is a key part of MR microscopy, enabling enhanced delineation of structures. Although excised brains allow agent to quickly penetrate into tissue, brains left in-skull are less susceptible to damage during tissue extraction and imaging, resulting in more accurate morphometric analyses. We sought to develop an optimised preparation and scanning protocol for imaging adult mouse brains in-skull, determining the timecourse for agent to penetrate into intact brain. Using this protocol we assessed phenotype in Tc1 mice – a model of Down Syndrome. We identified ventricular enlargement in 10 of 14 transgenic Tc1+ mice imaged. 1045. MR Microscopy of Zebrafish Miriam Scadeng 1 , Ellen Breen 2 , Nathan Gray 1 , David Dubowitz 1 1 Radiology, UC San Diego, San Diego, CA, United States; 2 Medicine, UC San Diego, San Diego, CA, United States Being a relatively new animal model there is no comprehensive 3D anatomical atlas onto which temporal or spatial data can be projected. In addition, methods for in-vivo imaging of adult fish are needed if zebrafish researchers are to benefit from functional MR imaging techniques such as MRS, MEMRI, BOLD and even ASL that are routinely being used in mouse models of disease. The major challenges include the very small size of the fish, and imaging the live fish in water. We present methods for in-vivo MRI of zebrafish, and a 3D atlas of zebrafish anatomy. 1046. Visualization of Vascular Casts Using 3D MR Imaging Ian Rowland 1 , Joseph Heintz 2 , Douglas Steeber 3 , Ralph Albrecht 2 1 Department of Radiology, University of Wisconsin, Madison, WI, United States; 2 Department of Animal Sciences, University of Wisconsin, Madison, WI, United States; 3 Department of Biological Sciences, University of Wisconsin, Milwaukee, WI, United States This study demonstrates that at 4.7T, using a standard 3D gradient echo sequence, images of vascular casts prepared using established corrosion casting techniques may be obtained with an isotropic resolution
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