Traditional Posters : Neuroimaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Neurodegenerative Diseases: Miscellaneous

Monday May 9th
Exhibition Hall  14:00 - 16:00

2204.   Imaging myelin water fraction to reveal novel aspects of cerebral pathology in motor neuron disease  
Shannon Kolind1,2, Sean Deoni2,3, Rakesh Sharma1,4, Melanie E Lord4, Steven Knight5, Kevin Talbot4, Heidi Johansen-Berg1, and Martin R Turner1,4
1FMRIB Centre, University of Oxford, Oxford, United Kingdom, 2Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom, 3Division of Engineering, Brown University, Providence, Rhode Island, United States, 4Oxford University Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom, 5OCMR, University of Oxford, Oxford, United Kingdom

Whole-brain multi-component relaxometry was applied to different phenotypes of motor neuron disease - amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), in comparison to healthy controls, as a potential surrogate marker of demyelination and inflammatory activity. With the aims of furthering understanding of pathology and phenotype variability, we found a distinct pattern of involvement between ALS and PLS. There was evidence of widespread inflammation in ALS, and more focal regions of demyelination in PLS. These preliminary findings may have relevance to the marked difference in prognosis between ALS and PLS.

2205.   The role of brain structure and executive function on visuoconstructional processing in late life depression 
Melissa Lamar1, Emma Rhodes1, Olusola Ajilore1, Aifeng Zhang1, Maria Caserta1, and Anand Kumar1
1Psychiatry, University of Illinois at Chicago, Chicago, IL, United States

Executive functioning appears key to successful visuoconstructional performance in aging but little is known about how it (or age-related alterations in brain structure) contribute to performance in late-life depression. We examined the role of executive functioning in visuoconstructional processing in late life depression and healthy aging taking into account age-related white matter and hippocampal volumes. Comparisons of 57 adults with late-life depression and 87 healthy controls did not reveal brain structure or function (i.e., visuoconstructional) differences; however, regression analyses revealed the importance of executive functioning and white matter volume to visuoconstructional performance in healthy controls but not in late-life depression.

2206.   Whole-brain Proton MRSI Data Analysis using a Corticospinal Tract Atlas in Amyotrophic Lateral Sclerosis 
Varan Govind1, Khema R Sharma2, Sulaiman Sheriff1, Gaurav Saigal1, and Andrew A Maudsley1
1Radiology, University of Miami, Miami, Florida, United States, 2Neurology, University of Miami, Miami, FL, United States

Brain metabolite levels in the motor cortex and corticospinal tracts in earlier studies were calculated using manually drawn regions-of-interest (ROI) in those structures. Such an ROI-based data analysis approach comes with subjectivity in drawing ROIs that result in higher data variability. In this study, a 3D brain white matter CST atlas was used to analyze whole-brain MRSI data, and to quantify metabolites, N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the left- and right whole-CSTs of subjects with ALS and controls.

2207.   Towards an Imaging-Metric for Pre-Symptomatic Manifestations of ALS 
Govind Nair1, Susan Gronka2,3, Debbie Lu2, Joanne Wuu2, Xiaoping P Hu1, and Michael Benatar2
1Biomedical Imaging and Technology Center, Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States, 2Department of Neurology, School of Medicine, Emory University, Atlanta, GA, United States, 3University of Miami, Miami, FL, United States

The neurodegenerative changes in amyotrophic lateral sclerosis (ALS) are believed to start before the clinical manifestation of symptoms. While MRI can detect these changes in clinically diagnosed ALS patients, we explored the use of a metric that combines multiple MRI parameters to detect the disease state in pre-symptomatic individuals. At least one principal component from T1 and DTI data from the cortico-spinal tract and motor cortex was a good indicator of the disease state when applied to a pre-symptomatic individual who progressed to ALS and 5 repeat-tested ALS patients. Additional studies are underway to validate this model.

2208.   Do age and long-term HIV infection control affect brain metabolites? 
Caroline Rae1, Lucette Adeline Cysique2, Jae Muyng Lee3, Tammy Lane4, Kirsten Moffat5, Andrew Carr6, and Bruce James Brew7
1Neurosciences Research Australia, University of New South Wales, Sydney, NSW, Australia, 2Brain Sciences, University of New South Wales, Sydney, NSW, Australia, 3Neurosciences Research Australia, University of New South Wales, Sydney, Australia, 4Psychology, Macquarie University, Sydney, Australia, 5Medical Imaging, St. Vincent's Hospital, Sydney, Australia, 6Immunology and Infectious Diseases, St. Vincent's Hospital, Sydney, Australia, 7Neurology, St. Vincent's Hospital, Sydney, Australia

To test whether age and immune status affect neurocognitive and metabolic outcomes in HIV infection, we examined 61 clinically stable, virally controlled HIV+ individuals aged > 45y, and 16 HIV-negative demographically-comparable controls using neuropsychological testing and 1H-MRS. While, most HIV+ individuals showed sub-clinical forms of neurocognitive impairment, we found evidence of neuronal loss density/dysfunction (reduced NAA) reduced brain metabolism (reduced Glx) and elevated myo-inositol/creatine in caudate nucleus - a subcortical region traditionally affected in HIV infection. We also identified these abnormalities in posterior cingulate cortex, an area known to be affected by pathological aging.

2209.   Assessment of Disease Severity in Late Infantile Neuronal Ceroid Lipofuscinosis Using Multiparametric MRI 
Jonathan P Dyke1, Dolan Sondhi2, Henning U Voss1, Dikoma C Shungu1, Xiangling Mao1, Kaleb Yohay3, Stefan Worgall3, Neil R Hackett2, Charlene Hollmann2, Mary E Yeotsas2, Stephen M Kaminsky2, Barry Kosofsky3, Linda A Heier1, Ronald G Crystal2, and Douglas Ballon1
1Radiology, Weill Cornell Medical College, New York, NY, United States, 2Genetic Medicine, Weill Cornell Medical College, New York, NY, United States, 3Pediatrics, Weill Cornell Medical College, New York, NY, United States

Five MR imaging biomarkers were combined into a single multivariate imaging metric that correlated with the clinical Weill Cornell LINCL score of disease severity. Whole brain assessment of apparent diffusion coefficient (ADC), fractional anisotropy (FA), MR spectroscopy (NAA/Cre Ratio), T2-measurement and % CSF volume were obtained on 10 subjects at various stages of Batten disease. The combined imaging metric correlated better with the LINCL score than individual measures alone. This resulted in a robust and objective assessment of whole brain degeneration independent of age that may be useful in serial monitoring of subjects during various therapy regimens.

2210.   Voxel-based T2 Relaxometry in Prion Disease 
Enrico De Vita1,2, Harpreet Hyare3,4, Chris Carswell3,4, Andrew Thompson3,4, Ana Lukic3,4, Tarek Yousry1,2, Peter Rudge 3,4, Simon Mead3,4, John Collinge3,4, and John Thornton1,2
1Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, United Kingdom, 2Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, 3MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom, 4National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, United Kingdom

Voxel-based analyses of T2 relaxometry data (VBR) has been used to assess pathological changes in temporal lobe epilepsy and other conditions. Prion diseases are progressive neurodegenerative disorders caused by accumulation of aggregates of an abnormally folded prion protein, and provide a molecular model for neurodegeneration. We applied for the first time quantitative cerebral T2 VBR to prion disease patients of different subtypes (symptomatic and asymptomatic inherited, and sporadic CJD) and compared the results to voxel based morphometry (VBM). T2-VBR (based on 3-minute acquisition protocol) identified areas of pathological change distinct to those indicated by VBM highlighting the differences between subtypes.

2211.   Glutamatergic and GABAergic neurotransmission in Manganism using 13C NMR Spectroscopy 
Anant Bahadur Patel1, and Puneet Bagga1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

In this study the effect of manganese induced neurotoxicity on neuronal and astroglial metabolism was evaluated by 13C NMR spectroscopy in conjunction with co-infusion of [U-13C6]glucose and [2-13C]acetate. In vivo 1H NMR spectroscopy suggested neurodegeneration in manganese treated mice. 13C Labeling data indicated impairment in glutamatergic, GABAergic and astroglial function in thalamus after chronic manganese treatment.

2212.   In vivo L-COSY Identifies Neurochemical Changes in Professional Athletes with Repetitive Head Injuries 
Alexander Peter Lin1, Saadallah Ramadan1, Robert A Stern2,3, Hayden Nicholas Box1, Peter Stanwell1, Ann C McKee2,3, Robert Cantu2, Christopher Nowinski2, and Carolyn Elizabeth Mountford1
1Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, 2Center for the Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, MA, United States, 3BU Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA, United States

Recent studies have shown one of the long term effects of repetitive head injury in professional athletes is the neurodegenerative disease of chronic traumatic encephalopathy characterized, post mortem, by abnormal tau accumulation in the brain. In this preliminary study, we use localized correlated spectroscopy (L-COSY) to identify multiple neurochemical species that demonstrate significant changes from cumulative head trauma. These changes include markers of diffuse axonal injury, glutamatergic dysfunction, alterations in excitatory, inhibitory, and structural amino acids and that would have been difficult to measure using conventional 1D MRS.

2213.   Distinct pattern of atrophy in the different phenotypes of progressive supranuclear palsy in magnetic resonance imaging 
Adriane Gröger1, Karin Srulijes1, Maksym Nechyporenko1, Elisabeth Dietzel1, Constantin Mänz2, Uwe Klose2, Walter Mätzler1, and Daniela Berg1
1Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University Tuebingen, Tuebingen, Germany, 2Department of Diagnostic and Interventional Neuroradiology, University Hospital Tuebingen, Tuebingen, Germany

Goal of this study was to investigate whether typical PSP midbrain atrophy patterns in MRI can be used to differentiate PSP phenotypes. 19 patients with two clinical PSP phenotypes were examined, rated for presenting atrophy patterns, and arranged into two subgroups. Differences in tissue microstructures were studied using VBM and DTI. Typical PSP midbrain atrophy patterns were found only for PSP-Richardson’s syndrome (RS) but not in PSP-parkinsonism (PSP-P). RS showed smaller midbrain and larger liquor volumes as well as larger grey matter and smaller white matter volumes compared to PSP-P. MD and FA values evaluated these findings.

2214.   Brain metabolites in myotonic dystrophy type 1: A 3.0 T proton magnetic resonance spectroscopy study 
Yuhei Takado1,2, Hironaka Igarashi1, Kenshi Terajima1,2, Takayoshi Shimohata2, Masaki Okubo1,3, Kouichirou Okamoto1,4, Masatoyo Nishizawa1,2, and Tsutomu Nakada1
1Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan, 2Neurology, Brain Research Institute, University of Niigata, Niigata, Japan, 3Institute of Medicine and Dentistry Basic Radiological Technology, School of Health Sciences, University of Niigata, Niigata, Japan, 4Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan

The purpose of this study is to seek cerebral abnormalities in myotonic dystrophy type1 (DM1) using 1H-MRS at a 3.0 T scanner. We performed Single-voxel 1H-MRS (frontal white matter and frontal cortex) and MRSI. Brain metabolites were correlated with frontal assessment battery (FAB). The ratio of NAA/Cr in the frontal cortex was negatively correlated with the number of trinucleotide cytosine-thymine-guanine repeats (r = -0.67, p < 0.05). The ratio of NAA/Cr in the frontal white matter was positively correlated with FAB (r = 0.62, p < 0.05). These results probably reflect the microenvironment of the CNS impairment in DM1 patients.

2215.   Distribution of diffusivity changes in subcortical deep gray matter in prion diseases 
Raffaele Lodi1, David Neil Manners1, Emil Malucelli1, Claudia Testa1, Giovanni Rizzo1, Sabina Capellari2, Rosaria Strammiello2, Giulia Pierangeli2, Pietro Cortelli2, Pasquale Montagna2, Bruno Barbiroli1, Caterina Tonon1, and Piero Parchi2
1MR Spectroscopy Unit, Dept. Internal Medicine, Aging and Nephrology, University of Bologna, Bologna, Italy, 2Neurological Sciences, University of Bologna, Bologna, Italy

Objectives. To assess the relationship between MD changes and prion disease (PD) subtypes in deep gray matter structures (DGM) . Methods. MD values were calculated in DGM in nine prion disease patients and 12 matched controls, using a completely operator-independent method. Results. MD values were reduced in the caudate and putamen of prion patients. Prion patients showed an increased variability of MD values in the basal ganglia and thalamus. Conclusions. MD values were increased in subtypes where there is little or no spongiosis, but variably reduced in basal ganglia of different sCJD sub-types all characterized by the presence of spongiosis

2216.   Changes in iron concentration of the basal ganglia in Huntington's Disease using magnetic field correlation 
Maarten J. Versluis1,2, Eve M. Dumas3, Simon J.A. van den Bogaard3, Andrew G. Webb1,2, Mark A. van Buchem1, Ellen P. 't Hart3, Matthias J.P. van Osch1,2, Jeroen van der Grond1, and Raymund A.C. Roos3
1Radiology, Leiden University Medical Center, Leiden, Netherlands, 2C.J. Gorter Center for high field MRI, Leiden University Medical Center, Leiden, Netherlands, 3Neurology, Leiden University Medical Center, Leiden, Netherlands

Increased iron in subcortical structures in patients with Huntington’s Disease (HD) has been linked to neurotoxicity and therefore suggested as a potential causal factor of the symptoms of HD. Using a novel MRI technique, Magnetic Field Correlation (MFC) changes in magnetic field inhomogeneities related to iron levels were measured. Increases in the magnetic field inhomogeneities were found in HD patients in the Caudate Nucleus and Putamen. These differences are likely to be caused by an increase in tissue iron concentration, and not by changes in water content or breakdown of myelin.

2217.   Assessment of Cerebral Blood Flow in Amyotrophic Lateral Sclerosis Using Arterial Spin Labeling MR Imaging 
Sumei Wang1, Lu Wang1, Hengyi Rao2, Zhengjun Li2, Lauren B Elman3, Leo F McCluskey3, Elias R Melhem1, Danny JJ Wang4, and John H Woo1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Neurology, Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia, PA, United States, 3Neurology, University of Pennsylvania, Philadelphia, PA, United States, 4Neurology, Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, CA, United States

The purpose of this study is to evaluate the utility of ASL for the detection of CBF abnormalities in patients with ALS. Twenty patients with ALS and 9 normal subjects were included in this study. Significantly reduced CBF in ALS patients compared with healthy subjects was found in bilateral sensorimotor cortex, superior temporal lobe, left anterior cingulate gyrus, calcarine and precuneus cortex. Our study indicates that ASL perfusion may be used as a potential biomarker for the diagnosis and monitoring of disease progression in ALS.

2218.   Asymmetric Characteristics of Hippocampus Perfusion and Its Response to Physostigmine Challenge in Gulf War Veterans 
Xiufeng Li1, Jeffrey Spence2, David M Buhner3, Robert W Haley3, and Richard W Briggs1,3
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 2Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, United States, 3Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

To test for hemispheric laterality of hippocampal abnormalities, the asymmetric characteristics of hippocampus perfusion and its response to physostigmine challenge in veterans with Gulf War Syndromes 1, 2 and 3 and healthy veterans were explored by asymmetry analysis, as expressed in asymmetry index, for measured hippocampus perfusion using arterial spin labeling. The observed hemispheric asymmetries in hippocampus perfusion in the veterans ill with Syndromes 2 and 3 might suggest the laterality of functional impairments. The differences of asymmetric characteristics across syndrome groups may imply distinctive pathological mechanisms.

2219.   Abnormal Striatal Functional Connectivity in Gulf War Illness: Effects of Modulating fcMRI Continuous States 
Kaundinya Gopinath1,2, Wendy Ringe3, Luo Ouyang1, Kirstine Carter3, Binod Thapa-Chhetry1, Lisa Butler1, Aman Goyal1, Parina Gandhi1, Yan Fang1, Sandeep Ganji1, Lei Jiang1, Saurabh Vaidya1, Richard Briggs1,2, and Robert Haley2
1Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 2Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States,3Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States

This study used functional connectivity MRI (fcMRI) to examine functional connectivity of the dorsal (DS) and ventral (VS) striatum in Gulf War Illness Syndrome 2 veterans (Syn2) and healthy controls, under three different continuous state conditions: eyes open resting (REST), visual fixation (FIX) and transcutaneous nerve stimulation (TENS). Results show that functional connectivity differences between controls and Syn2 seems to depend on the continuous state employed. During REST condition, Syn2 exhibited weaker striatal functional connectivity than controls to DMN. On the other hand, during FIX and TENS, DS functional connectivity to sensory and attention areas were significantly stronger in Syn2.

2220.   ASL Hippocampus Perfusion Imaging of Gulf War Veterans: Preliminary Results for National Survey Studies 
Xiufeng Li1, David M Buhner2, Robert W Haley2, and Richard Briggs1,2
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 2Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

To verify previously reported hippocampal blood flow abnormalities in ill Gulf War veterans selected from the 24th U.S. Naval Reserve Mobile Construction Battalion (CB), subjects were recruited from a representative national survey of over 8,000 veterans for arterial spin labeling hippocampus perfusion studies. The preliminary results reported here for the sickest of the three major Gulf War illness variants, Syndrome 2, confirm the abnormal hippocampus perfusion observed in Gulf War veterans ill with Syndrome 2 in the previous study of subjects in the CB cohort.

2221.   FMRI Reveals Abnormal Central Sensory Processing in Gulf War Illness 
Kaundinya Gopinath1,2, Lisa Butler1, Binod Thapa-Chhetry1, Aman Goyal1, Parina Gandhi1, Yan Fang1, Luo Ouyang1, Sandeep Ganji1, Lei Jiang1, Saurabh Vaidya1, David Buhner2, Wendy Ringe3, Richard Briggs1,2, and Robert Haley2
1Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 2Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States,3Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States

Previous studies have shown higher cooling and warming thresholds in hands and feet of Gulf War Illness (GWI) veterans. In this study, brain activation to innocuous and noxious heat stimuli was measured with a quantitative sensory testing (QST) fMRI paradigm, in GWI veterans with Syndromes1 (Syn1), Syn2 and Syn3, as well as age-matched controls. Syn1 and Syn3 groups exhibited significantly decreased brain activation during innocuous heat compared to controls. Further all three groups, Syn1, Syn2 and Syn3 exhibited decreased activation to noxious heat in a number of pain processing areas. The results indicate deficits in central sensory processing in GWI.

2222.   Basal ganglia NAA/Cr ratio and T2 differences in a population-representative sample of veterans with Gulf War Illness 
Sergey Cheshkov1,2, Audrey Chang2, Hyeonman Baek1,2, Jeffrey Spence3, Sandeep Kumar Ganji2, Evelyn Babcock2, Richard Wallace Briggs2,4, and Robert W Haley4
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 3Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, United States, 4Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

To determine the generality of lowered NAA/Cr previously measured at 1.5T in bilateral basal ganglia of Gulf War illness patients compared to healthy controls from a single battalion, 1H MRS at 3T of bilateral basal ganglia of control veterans and three illness variants (Syndromes 1, 2, 3) in a subset of subjects from a statistically representative national sample of 8,020 Gulf War veterans was performed. Consistent with previous studies, Syndrome 2 had significantly lower NAA/Cr in left basal ganglia than controls. Syndrome 3 had significantly lower Cho/Cr and significantly shorter Cho T2 in left basal ganglia than controls.

2223.   Fractional anisotropy is affected by white matter lesions in a TBSS study of Alzheimer’s disease 
Parnesh Raniga1, David Raffelt1, Alan Connelly2,3, Patricia Desmond4, and Olivier Salvado1
1CSIRO Preventative Health National Research Flagship ICTC, The Australian e-Health Research Centre, Brisbane, Queensland, Australia, 2Brain Research Institute, Florey Neuroscience Institutes (Austin), Melbourne, Victoria, Australia, 3Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia, 4Department of Radiology, University of Melbourne, Melbourne, Victoria, Australia

The impact of concomitant cerebral amyloid angiopathy (CAA) and related white matter hyperintensities (WMH) on the analysis of diffusion tensor imaging indices such as FA has not been fully explored in studies of Alzhimer’s disease (AD). In this study two groups of subjects with AD; with and without concomitant CAA were compared to normal controls (NC) using the tract based spatial statistics (TBSS) method. On average the groups with concomitant CAA had 15% more voxels that were significantly different from NC where those without CAA. These results suggest that WMH can have a considerable impact on analysis of FA.

2224.   The standard deviation (Asd, normalized relative anisotropy at 0 – 1 scale) detects neurodegenerative white matter lesions better than the fractional anisotropy (FA) 
Joong Hee Kim1, Jeffrey J. Neil2, and Sheng-Kwei Song1
1Radiology, Washington University, St. Louis, MO, United States, 2Neurology and Pediatrics, Division of Pediatric Neurology, Washington University, St. Louis, MO, United States

The main purpose of current study is to evaluate the sensitivity of diffusion anisotropy indices to white matter injury using rodent models of multiple sclerosis, globoid cell leukodystrophy, and amyotrophic lateral sclerosis, all of which cause spinal cord white matter injury. Our data show that fractional and relative anisotropy perform similarly, but relative anisotropy did better in distinguishing injury in areas of high anisotropy.

2225.   Longitudinal Evolution of MRI Parameters with Disease Progression in ALS 
Govind Nair1, Debbie Lu2, Margaret Walker2, John Carew3, Xiaoping P Hu1, and Michael Benatar2
1Biomedical Imaging and Technology Center, Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States, 2Department of Neurology, School of Medicine, Emory University, Atlanta, GA, United States, 3Biostatistics and Epidemiology, Carolinas HealthCare System, Charlotte, NC, United States

Longitudinal changes detected by T1 and DTI in the grey and white matter of patients with amyotrophic lateral sclerosis (ALS), a rapidly progressing neurodegenerative disease affecting the upper and lower motor neurons, are presented here. Several MRI parameters such as FA from the CST in the brain and cervical cord, and T1 in the motor cortices show changes that were significantly correlated with clinical markers of disease progression. A larger study, with longer duration of follow-up, is currently underway to further explore the potential of MRI as a biomarker of disease progression in ALS.

2226.   Predict the Response of Tinnitus to Cortical Stimulation Using Resting-State Functional MRI 
Gang Chen1, Brian Harris Kopell2, Wolfgang Gaggl3, Rey Ramirez4, Klaus Driesslein4, Sylvain Baillet1,4, Christopher R Butson2,4, and Shi-Jiang Li1,5
1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, 2Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, 3Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, 4Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, 5Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, United States

Epidural cortical stimulation (EpCS) has been demonstrated to be a potential therapeutic intervention for the suppression of severe tinnitus. However, individual response rates to EpCS vary substantially. It is suggested that tinnitus, in addition to the acoustic component, may have attentional and emotional components, and the insula and cingulate are involved in attention and emotion processing. In this study, we show that the EpCS effectiveness variation can be explained by the intersubject difference in functional connectivity between the insula, the cingulate and EpCS site. The stronger the connectivity, the more tinnitus can be alleviated by EpCS.

Traditional Posters : Neuroimaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Animal Models in Neurodegenerative Diseases

Tuesday May 10th
Exhibition Hall  13:30 - 15:30

2227.   Early anatomical and microstructural changes induced in rat brain by Vitamin A Deprivation: a longitudinal MRI study 
Bassem Hiba1, Bader Chaarani1, M. C. Beauvieux1, G Rafard1, Michèle Allard2, Alan Stephant1, Jean Michel Franconi1, and Jean Louis Gallis1
1UMR 5536 RMSB, CNRS-UB2, Bordeaux, France, 2UMR 5231, CNRS-UB2, Bordeaux, France

The aim of this work is to follow-up the earliest brain changes from the onset of vitamin A deprivation (VAD) in a rat model of brain degenerative process, using diffusion tensor imaging and anatomical MRI. 4 rats with VAD and 4 control rats were followed once a week along the first 6 weeks of VAD. This study demonstrated that the growth of total brain, striatum and hippocampus decreases from the 1st week, that dramatic increases in ventricular volumes occured at the 4th week and a significant decrease of the fraction anisotropy was detected only on the 6th week of VAD.

2228.   T1lower case Greek rho MRI as a Marker of Neurofibrillary Tangles in a Mouse Model of Alzheimer’s Disease 
Rachelle Berger1, Matthew Fenty2, Michiyo Iba3, Virginia M.-Y. Lee3, John A. Detre4, and Ari Borthakur2
1Biochemistry & Molecular Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States, 2CMROI, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States, 3CNDR, Department of Pathology & Lab Medicine, University of Pennsylvania School of Medicine, 4CfN, Department of Neurology, University of Pennsylvania School of Medicine

This study measures the efficacy of T1lower case Greek rho as a biomarker for tau pathology in the PS19 transgenic (Tg) mouse model of Alzheimer’s Disease (AD). While previous work has utilized only amyloid models of AD pathology, this animal model provides tantalizing possibility for investigating hyperphosphorylated tau protein that leads to intracellular neurofibrillary tangles using MRI for the first time. A significant decrease in T1lower case Greek rho relaxation time was measured in Tg mice brains relative to age-matched wild-type mice. The current study will generate crucial baseline values that can be assessed in this animal model in longitudinal studies that test novel therapeutic agents.

2229.   A diffusion kurtosis imaging (DKI) based correlate for plaque load in the APPPS1 mouse model for Alzheimer's disease (AD) 
Greetje Vanhoutte1, Sandra Pereson2, Bob Asselbergh2, Christine Van Broeckhoven2, and Anne-Marie Van der Linden1
1Biomedical Sciences, Bio-Imaging Lab, University of Antwerp, Antwerp, Antwerp, Belgium, 2Molecular Genetics, VIB and Institute Born-Bunge, University of Antwerp, Antwerp, Antwerp, Belgium

In vivo detection of the amyloid deposits in the brain would be beneficial in terms of AD diagnosis and therapy follow-up. The presence of amyloid deposits results in an increasing number of diffusion barriers and higher microstructural complexity. Our DKI results reinforce the hypothesis that DKI is a more sensitive technique than its predecessor DTI to depict changes in brain regions with amyloid deposits. In this in vivo study we observed higher kurtosis values in the brains of APPPS1 mice as compared to littermates.

2230.   Ultra High Field Magnetic Resonance Microimaging in Zebrafish Model of Cystic Leukoencephalopathy 
Alia Alia1, Haud Noémie2, Firat Kara1, and Adam Hurlstone2
1Leiden Institute of Chemistry, Leiden University, Leiden, South holland, Netherlands, 2University of Manchester, United Kingdom

Zebrafish is increasingly used as model organism for understanding various brain diseases including neurodegenerative disorders. Very recently the first zebrafish model for Cystic Leukoencephalopathy has been developed in which RNASET2 gene has been mutated. In this study we applied high resolution µMRI to visualize neurodegeneration in RNASET2 deficient zebrafish. T2-weighted MR imaging showed that RNASET2 deficient zebrafish exhibit frequent white matter anomalies which were scattered throughout the brain. T2 relaxation measurements suggest that theses lesions may be filled with CSF. Our results suggest that zebrafish model of Cystic Leukoencephalopathy develops similar lesions as found in human patients and show that µMRI can be successfully used to visualize neurodegeneration in zebrafish.

2231.   Changes in glucose level with age and its correlation with severity of plaque deposition in a transgenic model of Alzheimer’s disease 
Firat Kara1, Kristin Möbius1, Mark A van Buchem2, Huub JM de Groot1, Reinhard Schliebs3, and Alia Alia1,4
1Leiden Institute of Chemistry, Leiden University, Leiden, South holland, Netherlands, 2Department of Radiology, Leiden University Medical Centrum, Leiden, South holland, Netherlands,3Department of Neurochemistry, University of Leipzig, Leipzig, Germany, 4Department of Radiology, Leiden University Medical Centrum, Leiden, Netherlands

Glucose uptake and metabolism has been shown to be impaired during Alzheimer’s disease and is suggested to be an important cause of neurodegeneration. However the cause of impairment of glucose uptake/metabolism is AD brain and its correlation with plaque deposition is not clear. In this study, we longitudinally monitored, the change in glucose level in APPTG2576 mouse model of AD using in vivo MRS in conjunction with µMRI and ex vivo HR-MAS 1H MRS. Our results indicate that decline in glucose level occur primarily in plaque affected areas of the brain of APPTG2576 mice and show a temporal correlation between glucose decline and plaque deposition in AD brain.

Anne Bertrand1,2, Umer Khan2, Dung Minh Hoang2, Dmitry Novikov2, Pavan Krishnamurthy3, Hameetha Banu Rajamohamed Sait3, Benjamin Winthrop Little2, Einar M Sigurdsson3, and Youssef Zaim Wadghiri2
1URA CEA-CNRS 2210, MIRCen, Fontenay-Aux-Roses, France, 2Radiology, NYULMC, New York, United States, 3Physiology & Neuroscience, NYULMC, New York, United States

Our aim was to study in vivo the neuronal transport in a mouse model of tauopathy, using manganese-enhanced MRI (MEMRI). We show that 1) JNPL3[P301L] mice display a progressive impairment of neuronal transport with aging; 2) the degree of neuronal transport impairment is correlated with the level of tauopathy in neurons. Thus, MEMRI provides a useful biomarker that can be used during the pre-clinical evaluation of new drugs against Alzheimer’s disease.

2233.   Detection of Treatment Effects with 1H MRS in Transgenic Mouse Model of Alzheimer’s Disease 
Malgorzata Marjanska1, Stephen D Weigand2, Geoffry L Curran2, Thomas M Wengenack2, Joseph F Poduslo2, Michael Garwood1, and Clifford R Jack, Jr.2
1Radiology, University of Minnesota, Minneapolis, MN, United States, 2Mayo Clinic College of Medicine, Rochester, MN, United States

MRS was assessed as a non-invasive outcome measure capable of detecting metabolic alterations following passive immunization in a transgenic mouse model of Alzheimer’s disease (AD). Treatment of transgenic AD mice with either of two anti-A antibody regimes that have previously been demonstrated to reduce amyloid plaque load slowed the rate at which mIns normally increases in transgenic AD mice (APP-PS1) in a multi-dose treatment paradigm. 1H MRS may provide an in vivo measure of anti-Alower case Greek beta therapeutic efficacy in pre-clinical studies.

2234.   3D Quantitative Micro-MRI Mapping of Alzheimer’s Plaques in Transgenic Mice using Alower case Greek beta1-42 Targeted-USPIOs 
Dung Minh Hoang1, Jing Yang2, Lindsay K Hill1, Wai Tsui3, Yanjie Sun2, Yongsheng Li2, Mony De Leon3, Thomas Wisniewski2,3, and Youssef Zaim Wadghiri1
1Radiology, NYU School of Medicine, New York, NY, United States, 2Neurology, NYU School of Medicine, New York, NY, United States, 3Psychiatry, NYU School of Medicine, New York, NY, United States

Amyloid β (Aβ) plaques are one of the pathological hallmarks of Alzheimer’s disease (AD). Their visualization in the brain is very important to monitor AD progression and to evaluate the efficacy of therapeutic interventions. Numerous studies have investigated the visualization of Aβ plaques using MRI through endogenous detection both in human and in mouse brains. In the present study, we examined whether the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ1-42 peptide along with mannitol through femoral intravenous injection can be effective to detect individual plaques using in vivo µMRI and map the amyloid burden throughout the brain.

2235.   Response to Donepezil Challenge in Rat Brain by rCBV-based phMRI 
Thomas Kaulisch1, Holger Rosenbrock2, and Detlef Stiller1
1In-Vivo Imaging, Target Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, 2CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

Acetylcholinesterase inhibitors (AChEI) are used for the treatment of mild cognitive impairment (MCI) symptoms in Alzheimer’s disease. Pharmacological MRI (phMRI) can be used to study the dose-response relationship of a pharmacological challenge in the brain. The AChEI donepizil was studied with an rCBV-based MR read-out in rats at two doses (0.2 and 0.5 mg/kg) and compared to challenge with nicotine or the carboanhydrase inhibitor acetazolamid (ACZ); the latter testing the cerebral vascular reserve. A clear dose-response relation was observed being most pronounced in cortical regions. High dose of donepezil yielded changes in rCBV nearly reaching the vascular reserve.

2236.   Automatic Measurement of Atrophy Rates in Hippocampal Subfields from Longitudinal High-Resolution T2-weighted MRI 
Sandhitsu Das1, Brian Avants1, John Pluta1, Caryne Craige1, Michael Weiner2, Susanne Mueller2, and Paul Yushkevich1
1PICSL, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2VA Medical Center, University of California at San Francisco, San Francisco, CA, United States

We present the first attempt at measuring longitudinal atrophy rates within the subfields of the hippocampal formation from focal in vivo T2-weighted MRI (HF-MRI). Commonly used T1-weighted structural MRI does not have sufficient intensity contrast to distinguish subfields. In HF-MRI, on the other hand, subfields are distinguishable, but the image is highly anisotropic with high in-plane resolution in slices oriented perpendicular to the long axis of the hippocampus and thick slices -- this poses certain methodological challenges in processing HF-MRI data. We carefully adapt existing techniques to address these challenges and show that significant effects can be measured in a cohort of cognitively impaired patients in subfields such as CA1.

2237.   Feasibility of Detecting Preclinical Hippocampal Neuronal Cell Loss in Subjects Destined to Develop Alzheimer’s Disease 
Keith R Thulborn1, Debra Fleischman2, R Shah2, Ian C Atkinson1, and Aiming Lu1
1Center for Magnetic Resonance Research, University of Illinois at Chicago, Chicago, IL, United States, 2Rush Alzheimer's Disease Clinic, Rush University Medical Center, Chicago, IL

Alzheimer’s disease (AD) is a devastating neurodegenerative disease for which there is no early detection, no cure and no long lasting intervention. Early changes in cell density may offer an opportunity for detecting preclinical AD, a necessary first step design and evaluate interventions without the use of clinical disease as an outcome measure. We report on the use of quantitative sodium MR imaging for detecting cell density changes in the hippocampal regions of subjects with mild probable AD and mild cognitive impairment that can progress to AD.

2238.   A novel events-based model for mapping disease progression and its application to familial Alzheimer's disease 
Hubert Martinus Fonteijn1, Matt J Clarkson2, Marc Modat1, Josephine Barnes2, Manja Lehmann2, Sebastien Ourselin1, Nick C Fox2, and Daniel C Alexander1
1Computer Science, Centre for Medical Image Computing, London, United Kingdom, 2Institute of Neurology, Dementia Research Centre, London, United Kingdom

This abstract introduces a novel method for studying disease progression using cross-sectional data. The model describes disease progression as a series of events and treats each data point as a snapshot of this series. We calculate the probability that an event has happened and use a MCMC algorithm to construct plausible series of events from this probability. We demonstrate our model on serial T1 MRI data from a familial Alzheimer’s disease cohort. We calculate regional atrophy using non-linear registration methods and show progression of atrophy on a much finer level than previous studies, confirming progression patterns from pathological studies.

2239.   T2 alterations in ex vivo human brains with Alzheimer's disease pathology 
Robert J Dawe1, Julie A Schneider2, David A Bennett2, and Konstantinos Arfanakis1
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, 2Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Postmortem MRI of the human brain allows for comparison of imaging findings with histopathologic data, providing a unique opportunity to evaluate the sensitivity of new MRI techniques to tissue changes related to Alzheimer’s disease (AD) and other neurodegenerative diseases. The purpose of this work was to investigate differences in T2 relaxation times among postmortem brain specimens with low, intermediate, and high likelihood of AD, assessed histopathologically, according to the National Institute on Aging (NIA)-Reagan Institute criteria. T2 elevation was detected in periventricular and subcortical white matter regions, and T2 depression was detected in the globus pallidus and putamen.

2240.   Quantitative R2' mapping to investigate the relationship of brain iron deposition and cognitive impairment in Alzheimer disease 
Wenzhen Zhu1, and Lingyun Zhao2
1Department of Radiology, Tongji Hospital,Tongji Medical College, Wuhan, Hubei Province, China, People's Republic of, 2Department of Radiology, Tongji Hospital,Tongji Medical College

This study initially investigate the correlation of increased brain iron accumulation with the severity of cognitive impairment in patients with Alzheimer’s disease using advanced quantitative R2' mapping. The results revealed that R2' is a reliable parameter in measuring brain iron deposition in AD patients; Furthermore, regional R2' and brain iron concentration, especially which of bilateral hippocampus and parietal cortex, were significantly positive correlated with the severity of cognitive impairment, indicating that R2' can be used as an imaging marker to evaluate disease progression. R2' technique might provide exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for AD.

2241.   Automatic Segmentation of the Hippocampus in T1-Weighted MRI with Multi-Atlas Label Fusion Using Open Source Software: Evaluation in 1.5 and 3.0T ADNI MRI 
Jung Wook Suh1, Hongzhi Wang1, Sandhitsu Das1, Brian Avants1, and Paul A Yushkevich1
1PICSL, Radiology, University of Pennsylvania, Philadelphia, PA, United States

Hippocampal volume is arguably the most widely accepted MRI-based Alzheimer’s disease (AD) biomarker. We provide a highly reliable, open-source, validated turnkey software solution for automatic measurement of hippocampal volume and atrophy in T1 MRI data. Such tool will enable rapid analysis of imaging data for disease progression and treatment effect evaluation in clinical applications.

2242.   Magnetization Transfer Contrast (MTC) MRI for the Detection of Amyloid Accumulation in Alzheimer’s Disease 
Carlos J. Pérez-Torres1,2, and Robia G Pautler1,2
1Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, United States, 2Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States

Alzheimer’s disease (AD), the most common form of dementia, is an incurable and terminal progressive neurodegenerative disease. Accumulation of amyloid peptide is an early event in the disease and is one of the classical pathological hallmarks of AD. Magnetization Transfer Contrast (MTC) is a Magnetic Resonance Imaging (MRI) technique to specifically detect changes in macromolecule concentration. In this work, we show that MTC MRI is sensitive to large changes in amyloid as evidenced in a mouse model of advanced AD.

2243.   Patterns of white matter tract damage in behavioural variant of frontotemporal dementia and primary progressive aphasia: a DT MRI study. 
Elisa Scola1, Federica Agosta2, Elisa Canu2, Lidia Sarro2, Alessandra Marcone3, Chiara Cerami3, Giuseppe Magnani4, Francesca Caso4, Stefano Francesco Cappa3,5, Massimo Filippi2, and Andrea Falini1,6
1Neuroradiology - CERMAC, San Raffaele Scientific Institute, Milan, Italy, 2Neuroimaging Research Unit, Scientific Institute and University San Raffaele Hospital, Milan, Italy, 3San Raffaele Turro Hospital, Department of Clinical Neurosciences, Milan, Italy, 4Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University San Raffaele Hospital, Milan, Italy, 5Vita Salute University and Department of Clinical Neurosciences, San Raffaele Scientific Institute, Milan, Italy, 6Vita Salute University, San Raffaele Scientific Institute, Milan, Italy

The aim of this study was to assess the patterns of white matter (WM) tract damage in behavioural variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). WM damage was investigated globally in a voxel-by-voxel analysis as well as in specific fibre tracts. DT MRI demonstrated specific patterns of WM damage in bvFTD and PPA patients. Although WM abnormalities mirrored the patterns of grey matter (GM) atrophy, diffusivity changes were also identified in more posterior brain regions, which may be atrophied later in the course of the disease.

Traditional Posters : Neuroimaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
MRS of Animal Brain (except Cancer)

Wednesday May 11th
Exhibition Hall  13:30 - 15:30

2244.   Combined 1H MRS and Near-Infrared Spectroscopy Measurements of Cerebral Blood Volume, Oxygenation, Cytochrome Oxidase, and Intracellular Metabolites During Perinatal Hypoxia-Ischaemia 
Alan Bainbridge1, Ilias Tachtsidis2, Stuart Faulkner3, Sonya Mahony2, David Price1, David L Thomas4, Ernest B Cady1, Nicola J Robertson3, and Xavier Golay4
1Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London, United Kingdom, 2Department of Medical Physics and Bioengineering, University College London, London, United Kingdom,3Institute for Women’s Health, UCL, London, United Kingdom, 4Institute of Neurology, UCL, United Kingdom

To investigate brain haemodynamic and metabolic changes during hypoxia-ischemia (HI) and recovery we integrated broadband near-infrared spectroscopy (NIRS) with proton magnetic resonance spectroscopy (MRS). Experiments were performed under UK Home Office guidelines on a healthy piglet. The NIRS optodes were integrated with a surface coil and fixed on the top of the piglet’s head. We measured Lactate/N-acetyl-aspartate ratio using MRS and cerebral blood volume (CBV), cerebral oxygenation and the redox state of cytochrome-c-oxidase (ox-redCCO) using NIRS. NIRS provides complementary information to 1H MRS that may improve our understanding of the response of the newborn brain to HI.

2245.   Can 1H MRS be a Surrogate for 31P MRS in Quantification of Transient Hypoxic-Ischemic Insult Severity in a Neonatal Encephalopathy Model? 
Alan Bainbridge1, Stuart Faulkner2, Dorottya Kelen2, Manigandan Chandrasekaran2, David Price1, David L Thomas3, Ernest B Cady1, Nicola J Robertson2, and Xavier Golay3
1Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London, United Kingdom, 2Institute for Women’s Health, UCL, London, United Kingdom, 3Institute of Neurology, UCL, United Kingdom

In this study we correlated 1H MRS Lac/Naa with 31P metabolite ratios in order to assess whether 1H MRS could facilitate titration of hypoxia-ischemia (HI). Thirteen healthy piglets were studied. Transient cerebral HI was induced by reducing the inspired oxygen fraction inflating bilateral carotid artery occluders for ~ 25 min. 10 piglets were monitored with 31P MRS and the other 3 were monitored with 1H MRS during and after HI. Correlating median timecourses suggests that Lac/Naa is not a direct marker of either energy reserve or status. However, 1H MRS is potentially useful for quantifying insult severity.

2246.   In vivo measurements of cerebral ascorbate increases after systemic ascorbate infusion 
In-Young Choi1,2, Wen-Tung Wang1, Joanne Marcario1, Mark Levine3, and Phil Lee1,4
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, 2Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States, 3Molecular and Clinical Nutrition Section, National Institute of Health, Bethesda, MD, United States, 4Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Ascorbate (Ascorbic acid or vitamin C), a critical antioxidant, is most concentrated in the brain. However, However, the mechanism of cellular accumulation of ascorbate in the CNS has not been clearly demonstrated. In this study, we aim to measure cerebral ascorbate levels under the high concentration gradients between blood and the brain in order to investigate whether ascorbate levels can be modulated in the brain in vivo via intraperitoneal (i.p.) infusion using ultra-short echo time 1H MRS at 9.4 T.

2247.   Isoflurane Elevates Brain Lactate in a Dose-dependent Manner: A Localized 1H MRS Study of Mouse Brain In Vivo 
Susann Boretius1, Roland Tammer1,2, Thomas Michaelis1, and Jens Frahm1
1Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut fuer biophysikalische Chemie, Göttingen, Germany, 2DFG Research Center for Molecular Biology of the brain (CMPB), Göttingen, Germany

Volatile anesthetic drugs like isoflurane are widely used in animal research and human medicine. Here, we evaluated the influence of isoflurane on brain lactate and other cerebral metabolites in comparison to intravenous anesthetic drugs using in vivo localized proton MRS of healthy mice. Isoflurane provoked a reversible dose-dependent elevation of lactate concentrations, which was accompanied by increases of alanine, reductions of glucose, and a shift from phosphocreatine towards creatine. These findings may be of crucial importance not only for animal studies of brain metabolism, but also for human anesthesiology.

2248.   Effect of nicotine on glutamatergic and GABAergic neurotransmission in developing brain 
Anant Bahadur Patel1, and Mohammad Shameem1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Neurological changes associated with nicotine exposure during gestation and lactation is not properly understood. In this study we have used a novel approach of co-infusion of [U-13C6]glucose and [2-13C]acetate to investigate the effect of nicotine on glutamatergic and GABAergic neurotransmission in developing brain. The glutamatergic and astroglial energy consumption and the corresponding neurotransmission were increased significantly in cortical and subcortical brain regions of pups exposed with nicotine during gestation and lactation period.

2249.   1H-MRS profiling of the developing rat brain 
Serguei Liachenko1, and Jaivijay Ramu1
1FDA / NCTR, Jefferson, AR, United States

Developmental neurotoxicity is very important part of the evaluation of the new drug safety and is usually assessed using conventional histological and biochemical methods. Current study represents the first step in establishing the baseline for developmental neurotoxicology research using non-invasive imaging/spectroscopy techniques, which offer the opportunity to improve effectiveness and reduce animal use in such research. 1H-MRS methodology has a potential to improve our understanding of brain maturation and provides promising tool for development and qualification of new translatable non-invasive biomarkers

2250.   Acute restraint stress-induced change in glutamate neurotransmission in rat brain: An in vivo 1H-MRS study 
Sang-Young Kim1, Eun-Ju Jang2, Kwan-Soo Hong2, Chul-Hyun Lee2, Do-Wan Lee1, Chi-Bong Choi3, and Bo-Young Choe1
1Department of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea, Republic of, 2The Korea Basic Science Institute, Korea, Republic of, 3Department of Radiology, Kyunghee University Medical Center, Korea, Republic of

The present study investigated to determine whether acute restraint stress causes the changes in neurotransmitter level, especially glutamate, in rat brain and whether the acute stress-induced changes in brain metabolism can be recovered during the rest. In vivo proton spectra obtained from prefrontal cortex and hippocampus using 4.7 T animal magnet revealed significantly increased glutamate concentrations in rats exposed to acute restraint stress. However, the increased glutamate level in both brain regions could not be recovered during 1 hour rest. Our results suggest that glutamate neurotransmission in the prefrontal cortex and hippocampus be strongly implicated in regulating of stress response.

2251.   Neurochemical changes in olfactory system and hippocampus regions of Tau transgenic mice using 1H MRS 
Jieun Kim1, In-Young Choi1,2, Karen Duff3, and Phil Lee1,4
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, 2Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States, 3Department of Integrative Neuroscience, Columbia University Medical Center, New York, NY, United States, 4Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Effects of tauopathies in neurochemical levels of AD brain are not well understood. Tau transgenic mice (rTau) express a repressible human tau variant develop progressive age-related NFTs, neuronal loss, and behavioral impairments. In this study, we characterized neurochemical alterations associated with the development of Tau pathologies in the hippocampus and the olfactory bulbs (OB) of rTau transgenic mice. The results show that significant neurochemical changes occur in OB of rTau mice compared with wildtype.

2252.   Measurement of Metabolic Rates in Rat Olfactory Bulb by 1H and 1H-[13C] NMR In Vivo 
Golam M.I. Chowdhury1, Graeme F Mason1, Kevin L Behar1, Douglas L Rothman1, and Robin A de Graaf1
1MRRC, Yale University School of Medicine, New Haven, Connecticut, United States

MR spectroscopy of the olfactory bulb is particularly challenging due to its small size and proximity to bone and nasal cavities, distorting field homogeneity with loss in sensitivity and resolution. Using optimized shimming and adiabatic pulse sequences at 9.4 Tesla, we obtained high quality 1H MR spectra of GABA (J-edited) and 1H-[ 13C]-MRS of 13C labeled metabolites and measured the rates of glucose and acetate metabolism in olfactory bulb. Metabolic fluxes were determined by fitting a three-compartment metabolic model to time courses of 13C labeling of brain glutamate and glutamine measured from rats OB receiving timed infusions of [1,6-132]glucose or [2- 13C]acetate.

2253.   In Vivo Assessment of Neuronal Metabolic Fluxes in Mouse Brain by 1H-[13C] NMR Spectroscopy 
Lijing Xin1, Hongxia Lei2, Bernard Lanz2, and Rolf Gruetter1,2
1Department of Radiology, University of Lausanne, Lausanne, Vaud, Switzerland, 2Laboratory of functional and metabolic imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

13C MRS combined with the administration of 13C labeled substrates for transgenic mouse models will provide insights into the metabolism in brain pathologies. In the present study, separated 13C labeling turnover curves of GluC4, GlnC4, GlxC3 and LacC3 were obtained in mouse brain in vivo at 14T by 1H-[13C] MRS, which allows us to determine metabolic fluxes without additional blood sampling. This study can be extended to transgenic mouse models for further investigation of brain pathologies.

2254.   Simultaneous dection of metabolism of [2-13C]lactate and uniformly labeled glucose in the brain using in vivo 13C MRS 
Yun Xiang1, and Jun Shen1
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

Simultaneous detection of metabolism of [2-13C]lactate and uniformly labeled glucose in the brain using in vivo 13C MRS Yun Xiang, Jun Shen Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States In the carboxylic/amide region, brain 13C signals can only have one one-bond 13C-13C homonuclear couplings. As such only doublets (with a 13C-13C coupling of ~50 Hz) and singlets exist in this region. The large one-bond 13C-13C J couplings and the lack of interference from other isotopomers provide a unique condition for simultaneous detection of metabolism of different substrates. Intravenous co-infusion of [13C6]-D-glucose and [2-13C] lactate is used to demonstrate simultaneous detection of their metabolism. A significant contribution to brain energy metabolism from lactate was found even at the high blood glucose level of 18.5 ± 1.7 mM, suggesting that lactate is a necessary component of brain energy substrates.

2255.   Non-invasive monitoring of antioxidant prodrug metabolism in rat brain by in vivo 13C MRS 
Peter Edward Thelwall1, Daniel Clark2, Susan M Ludeman3, James B Springer4, Michael A D'Alessandro3, Nicholas E Simpson2, Roxana Pourdeyhimi5, C Bryce Johnson5, Stephanie D Teeter5, Stephen J Blackband2, and Michael P Gamcsik5
1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, 2University of Florida, 3Albany College of Pharmacy and Health Sciences,4Duke University Medical Centre, 5Joint Department of Biomedical Engineering, University of North Carolina / NC State University

Glutathione is an endogenous antioxidant involved in protecting tissues from oxidative stress. Oxidative stress plays a role in some neurodegenerative processes, and therapeutic strategies to combat brain oxidative stress have included raising glutathione concentration. OTZ is a cysteine precursor that can elevate glutathione levels in some tissues. We synthesised 13C-OTZ and tracked its uptake and metabolism in vivo using 13C MRS. The effect of OTZ on brain glutathione content was assessed, and the metabolic fate of 13C-OTZ elucidated from in vivo and ex vivo spectroscopy and mass spectrometry of rat brain.

2256.   Direct assessment of increased pyruvate carboxylase in the hyperammonemic brain using 13C MRS 
Bernard Lanz1, Cristina Cudalbu1, João Miguel Duarte1, and Rolf Gruetter1,2
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Department of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

Dynamic 13C MRS using [1,6-13C2] glucose allows non-invasive measurement of the neuroglial metabolism in vivo. In this study, we coupled [1,6-13C2] glucose with ammonium chloride infusion in rats in order to assess the effect of hyperammonemia on neuronal metabolism. While total glutamine was linearly increasing, the glutamine 13C enrichment curves were nevertheless reaching a dynamic steady-state in about 4 hours. From the fractional enrichment at steady-state of GluC4, GlnC4, GluC3 and GlnC3, we conclude that neuronal metabolism is hardly effected by hyperammonemia, while the glial pyruvate carboxylase activity increases significantly, as visible on the strongly diluted GlnC3.

2257.   SNR improvement of a 13C-cryo-coil in comparison with room-temperature coils 
Markus Sack1, Friedrich Wetterling2, Gabriele Ende1, L R Schad2, and Wolgang Weber-Fahr1
1Neuroimaging, Central Institute of Mental Health, Mannheim, Germany, 2Computer Assisted Clinical Medicine, University Medical Center Mannheim, Mannheim, Germany

Each MR procedure, whether an imaging or spectroscopic method, benefits from an improved signal-to-noise ratio (SNR). This is especially true measuring signals of 13C, because the low Larmor frequency and natural abundance result in a reduced SNR. We compared two room-temperature coils with a newly acquired helium cooled low temperature 13C-cryo-coil and found a gain of at least 6.3 in phantom measurements. The SNR gain allows considerably shorter acquisition times and higher spatial resolution. Additionally the high Q-factor of the coil allows the application of comparable short RF pulses and thus can increase the bandwidth of the signal excitation.

2258.   Transverse relaxation times of strongly J-coupled metabolites with LASER and CP-LASER in the rat brain. 
Dinesh K Deelchand1, Pierre-Gilles Henry1, Kamil Ugurbil1, and Malgorzata Marjanska1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

This study demonstrates that the increase in transverse relaxation times is higher for strongly J-coupled resonances than for singlet and weakly J-coupled resonances when incorporating the CP pulse train (non-selective adiabatic full passage pulses) within the LASER sequence in the rat brain.

Traditional Posters : Neuroimaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Animal Models of Brain Disease Other than Stroke
Thursday May 12th
Exhibition Hall  13:30 - 15:30

2259.   Retrograde neuronal injury in response to glutaric acid in Glutaric Acidemia type 1 (GA-1) mouse model 
Jelena Lazovic1, William J Zinnanti2, Xiaowei Zhang3, and Russell Jacobs3
1Radiology, University of California, Los Angeles, Los Angeles, CA, United States, 2Neurology, Stanford, Palo Alto, CA, United States, 3California Institute of Technology

The aim of this work was to investigate whether local increases in glutaric acid, a metabolite that accumulates in glutaric academia type 1 (GA-1), can lead to retrograde neuronal injury. In this metabolic disorder, the striatum appears to be highly vulnerable brain region, without apparent high glutaric acid content. We hypothesized that increase in glutaric acid levels in areas outside the striatum can cause distal striatal injury. The addition of glutaric acid to the thalamus, induced neuronal injury in the substantia nigra, while cortical injection of glutaric acid resulted in localized striatal injury.

2260.   Use of volumetric MRI to characterize treatment effect and phenotype in a transgenic mouse model of tau pathology 
Sangeetha Somayajula1, Belma Dogdas1, Xiaohai Wang2, Mansuo Hayashi2, Shubing Wang3, Sofia Apreleva3, Richard Baumgartner3, Denise Welsh4, Xiangjung Meng4, Diane Posavec4, Amy Vanko4, Jacquelynn Cook4, Donald S Williams4, and Alexandre Coimbra4
1Informatics IT, Merck and Co., Inc, West Point, PA, United States, 2Neurology, Merck and Co. Inc, West Point, PA, 3Biometrics, Merck and Co. Inc, 4Imaging, Merck and Co. Inc

We study the use of volumetric MRI (vMRI) for characterization of longitudinal changes, response to therapy, and relationship between vMRI measurements and post-mortem biochemical measurements, in the rTg4510 transgenic mouse model for Alzheimer's disease. We use a low resolution (0.2 mm isotropic), high throughput imaging sequence and automated atlas based segmentation to measure volumes of regions of interest (ROIs) over time and across groups (positive and negative controls, and test compound). The data acquisition and analysis is sensitive to positive control therapy and also highlight specific brain ROIs that respond to therapy and show high correlation with biochemical phenotype.

2261.   Microanatomical correlates of Multi-exponential T2 and Quantitative MT in Pathological Rat Spinal White Matter 
Kevin D Harkins1,2, William M Valentine3, Daniel F Gochberg1,2, and Mark D Does1,4
1Institute of Image Science, Vanderbilt University, Nashville, TN, United States, 2Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 3Pathology, Vanderbilt University, 4Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

Multi-exponential T2 (MET2) and quantitative magnetization transfer (qMT) provide measures of myelin content but also differentially report on other characteristics of white matter micro-anatomy. This study reports MET2 and qMT findings in rat spinal cord with hexachlorophene(HCP)-induced lesions. The myelin water fraction and macromolecular pools size ratio measured by MET2and qMT, respectively, decrease with the introduction of HCP, and third T2 component is introduced. Future work will employ numerical simulations to correlate HCP-induced microstructural lesions with MET2 and qMT measurements.

2262.   Early MRI-visible lesions in Plasmodium berghei ANKA-induced cerebral malaria 
Raman SAGGU1, Dorothee FAILLE2, Georges GRAU2, Patrick COZZONE1, and Angele VIOLA1
1Université de la Méditerranée-Faculté de Médecine, CRMBM UMR CNRS 6612, Marseille, France, 2Department of Pathology, Sydney Medical School, The University of Sydney, Camperdown, Australia

Cerebral malaria (CM) is the most lethal complication of Plasmodium infection. We have previously characterized murine CM at its ultimate stage using in vivo MRI and MRS at 4.7 T, and proved the fatal role of ischemic edema. Here, our purpose was to detect clinically-relevant markers of early CM using T1- and T2-weighted MRI at higher field (11.75 T). We have identified early features of experimental CM such as damage to the internal capsule, and the optic and trigeminal nerves at high field. These findings may help understand the contribution of cerebral lesions to overt clinical signs during early CM.

2263.   Preliminary studies to assess CMRO2 with integrated T1 rho MRI and hybrid DRS/DCS optical approach in clinical scanners 
Victor Babu Kassey1, Wesley Baker2, Rickson C Mesquita2, Erin Buckley Buckley2, Joel H Greenberg3, Eric A Mellon1, Damodar C Reddy1, Arjun .G.Yodth G Yodth2, John A Detre4, Mark A Elliott1, and Ravinder Reddy1
1CMROI-Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2Department of Physics & Astronomy, University of Pennsylvania, 3Department of Neurology, University of Pennsylvania, 4Cerebrovascular Research Center, University of Pennsylvania, Philadelphia, United States

CMRO2 measurements are important in physiology. We have been working on T1ĉ based indirect detection of CMRO2 on swine, a large animal model with a lung capacity comparable to humans. Though the recirculation delay for 17O is known no group has worked on 17O2 delivery in a large animal model with fast MRI combining with optical techniques to measure CMRO2 from the pre-recirculation time. In the present study, a combined integrated T1ĉ MRI and Optical protocol has been designed to measure CMRO2 in young adult swine using two independent methods simultaneously on clinical MR scanners with the goal of future studies with humans.

2264.   Reduction in CSF Pulsatility with Altered Intracranial Compliance by Craniectomy in Communicating Hydrocephalus 
Shams Rashid1, James P McAllister2, Martin Schuhmann3, and Mark Wagshul4
1Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, 2Primary Children's Medical Center, University of Utah, Salt Lake City, UT, United States, 3Klinik für Neurochirurgie, Eberhard Karls Universität, Tübingen, Germany, 4Gruss MRRC, Albert Einstein College of Medicine, Bronx, NY, United States

Communicating hydrocephalus (CH) is characterized by elevated CSF aqueductal pulsations, and is thought to be caused by reduced intracranial compliance. This study investigates the effect of increasing intracranial compliance by decompressive craniectomy on CSF pulsatility in CH. CH is induced in rats by kaolin injection. Animals are subjected to craniectomy two weeks post induction. CSF pulsatility, measured by a cardiac gated phase contrast MR sequence, is found to decrease after craniectomy. This shows that intracranial compliance is linked to CSF pulsatility, and may play a key role in the development of CH.

Hilit Levy1, Yaniv Assaf1, and Dan Frenkel1
1Neurobiology, Tel Aviv University, Tel Aviv, Israel

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to pathologic changes in white matter (WM). In most MS mouse models, the neurologic damage mostly affects the spinal cord with limited damage to the brain. Here we induced experimental allergic encephalomyelitis (EAE) on non-obese diabetic (NOD) mice which are known to develop spontaneous autoimmune diabetes. We characterized the progression of the disease with MRI by T1-Gd and DTI acquisitions. Brain lesions have been detected by MRI and histology in WM and in gray matter similar to the findings of MS in humans.

2266.   Effects of cortical spreading depression on blood-brain barrier permeability in a mouse model of familiar hemiplegic migraine 
Dana Suciu Poole1, Johannes Rolf Sikkema2, Reinald Shyti3, Arnoldus M van den Maagdenberg3, Helga Eveline de Vries4, and Louise van der Weerd2,5
1Radiology, Leiden University Medical Centre, Leiden, Netherlands, 2Radiology, Leiden University Medical Centre, Netherlands, 3Human Genetics, Leiden University Medical Centre, Netherlands,4Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, Netherlands, 5Anatomy and Embriology, Leiden University Medical Centre, Netherlands

In a transnsgenic mouse model for familial hemiplegic migraine spreading depression (CSD) frequency and propagation speed are increased, and post-CSD neurological deficits are more severe and prolonged. In this study we induce CSD unilaterally in the mouse brain and show using a combination of gadolinium-enhanced MRI and histology that CSD induction in heterozygote mice causes severe unilateral BBB disruption in the cortex and hippocampus, which lasts >9 days. Histology confirms blood-brain barrier leakage.

2267.   MRI Reveals Differences in Neuroanatomy of Mouse Models of NPC Disease 
John Totenhagen1, Eriko Yoshimaru1, Ivan Borbon2, Christy Howison3, Robert Erickson2, and Theodore Trouard1
1Biomedical Engineering, University of Arizona, Tucson, Arizona, United States, 2Pediatrics, University of Arizona, Tucson, Arizona, United States, 3Arizona Research Laboratories, University of Arizona, Tucson, Arizona, United States

Niemann Pick Type C (NPC) disease is a rare genetic neurodegenerative disease with no effective treatment or cure. The commonly used mouse model of NPC disease (Npc1-/-) has been employed in many treatment studies and shows drastic dysmyelination and increased ventricular volume compared to control mice. A new mouse model of NPC disease has recently been made available which more closely mimics the genetic defect found in human NPC disease. MRI measurements of this new mouse model are presented here for the first time and show marked differences, particularly in white matter regions, compared to the Npc1-/- mouse.

2268.   Reduction of contralateral white matter volume after experimental focal epilepsy and hemispherectomy in rats 
Willem M Otte1,2, Kajo van der Marel2, Kees P.J. Braun1, and Rick M Dijkhuizen2
1Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands, 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

White matter volume changes as a result of focal epilepsy and epilepsy surgery. However, the direction, extent and time course of these changes remain unknown. We characterized serial white matter volumes in the contralateral hemisphere in a model of focal epilepsy and hemispherectomy in rats. Substantial differences in white matter volumes of the ‘healthy’ hemisphere were found in rats with a contralateral epileptic focus. In addition we found contralateral volume changes after hemispherectomy. These results imply that the interpretation of volume changes occurring after epilepsy surgery is complicated. Multiple factors influence structural alterations in the remaining brain.

2269.   Long term observations on status-epilepticus induced neurodegeneration: A 7Tesla MR study in a rat model 
Martin Meier1, Jens P. Bankstahl2, Marion Bankstahl2, and Xiao-Qi Ding3
1Small Animal Imaging Facility, Hannover Medical School, Hannover, Germany, 2Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany,3Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany

Long term observations in a rat model of epilepsia show structural changes in the brain even after 3 months after status-epilepticus.

2270.   Metabolic and morphological characterization of the Mecp2-308 truncated mouse model of Rett syndrome: effects of a treatment activating Rho GTPases 
Rossella Canese1, Bianca De Filippis1, Carla Fiorentini2, Alessia Fabbri2, Paola Porcari1, Laura Ricceri1, and Giovanni Laviola1
1Cell Biology and Neurosciences Dept., Istituto Superiore di Sanità, Rome, RM, Italy, 2Therapeutic Research and Medicine Evaluation Dept., Istituto Superiore di Sanità, Rome, RM, Italy

Rett syndrome (RTT) is a pervasive developmental disorder caused by a mutations in the gene encoding methyl−CpG−binding protein 2 (MeCP2). Here we investigated the effects of Cytotoxic Necrotizing Factor 1 (CNF1, a bacterial toxin that enhances neurotransmission and synaptic plasticity) administration to contrast the RTT phenotype in MeCP2-308 truncated mice, by in vivo 1H MRI and MRS. Our data indicate that CNF1 treatment affects metabolism of taurine and inositol. In the MeCP2-308 phenotype these effects lead to a normalization towards wt-like values. MRI analysis revealed also a significant reduction of the corpus callosum, in agreement with MRI results in patient.

2271.   Molecular imaging of inflammation in a cerebrovascular aneurysm model. 
Alexei A Bogdanov1, Matthew J Gounis2, Ronn Walvick2, and Ajay K Wakhloo2
1Radiology, UMASS Medical School, Worcester, MA, United States, 2UMASS Medical School

We investigated the use of myeloperoxidase-specific paramagnetic substrate for imaging local inflammation created in the vascular wall of a model aneurysm. We used in situ incubation of LPS solution via temporal acclusion of aneurysm with a balloon catheter followed by MRI imaging prior and post IV injection of MPO substrate. The comparison of normalized changes of MR SI ratios suggested that a realistic animal model of cerebrovascular aneurysm enables testing of inflammation-modulated factors of aneurysmal instability that potentially leads to a rupture in human patients.

2272.   Reduced functional connectivity in normal aging in non-human primates 
Alexandre Coimbra1, Dai Feng2, Marie Holahan1, Jacquelynn Cook1, Donald Williams1, and Richard Baumgartner2
1Imaging, Merck & Co, Inc, West Point, PA, United States, 2Biometrics, Merck & Co, Inc, Rahway, NJ, United States

In this work we explored the correlation between age and functional connectivity in lightly anesthetized Rhesus monkeys. Functional connectivity was expressed as goodness-of-fit (GOF) scores in the Posterior-cingulate cortex (PCC) a component region in the Default Mode Network. In humans, GOF in the DMN decreases with age. Overall, our results are in agreement with previously published results in humans; similarities exist between the characteristics of low frequency fluctuations of BOLD signal in awake humans and lightly anesthetized Rhesus monkeys suggesting the possible use of Rhesus macaques and GOF functional connectivity in translational investigations of age-related neurological disorders.

2273.   Characterization of Lesions and Regional Brain Tissue of ArcAbeta Mice Based on Magnetic Susceptibility 
Andreas Deistung1, Jan Klohs2, Ferdinand Schweser1, Joanes Grandjean2, Marco Dominietto2, Conny Waschkies2, Roger M Nitsch3, Markus Rudin2,4, and Jürgen R Reichenbach1
1Medical Physics Group, Department of Diagnostic and Interventional Radiology I, Jena University Hospital, Jena, Germany, 2Institute for Biomedical Engineering, ETH & University of Zürich, Switzerland, 3Division of Psychiatry Research, University of Zürich, Switzerland, 4Institute of Pharmacology and Toxicology, University of Zürich, Switzerland

This study aims at optimizing quantitative susceptibility mapping (QSM) for high resolution MR imaging of mice brains and evaluating its potential to characterize the punctuate lesions in the brain of arcAβ mice. Furthermore, the regional differences of the brain tissue iron load are investigated in both living transgenic arcAβ (n=3) mouse and wild type (n=6) controls. VOI-based analysis of cortical, hippocampal, thalamic and white matter tissue revealed no significant differences in magnetic susceptibilities between brain regions in arcAβ compared to wt mice. However, a tendency of regional variances of magnetic susceptibility values in lesions was found.

2274.   Voxel-based morphometry reveals localised cerebral atrophy in a mouse lemur model of aging 
Stephen John Sawiak1,2, and Marc Dhenain3
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England, United Kingdom, 2Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom, 3MIRCen, I2BM Institute of Biomedical Imaging, Fontenay aux Roses, France

Voxel-based morphometry is applied to 30 mouse lemur brains of ages 2-11 years and shows localised changes with age, of particular note cingulate and entorhinal cortical reductions in grey matter concentrations are seen. This shows that automated techniques can be applied in this area leading to greater sensitivity with less manual bias.

2275.   Cortical Atrophy in Experimental Autoimmune Encephalomyelitis 
Allan J MacKenzie-Graham1, Gilda A Rinek1, Stefan M Gold2, Andrew J Frew1, Cynthia Aguilar3, David R Lin1, Elizabeth Umeda1, Rhonda R Voskuhl1, and Jeffry R Alger1
1University of California, Los Angeles, Los Angeles, CA, United States, 2Universität Hamburg, Hamburg, Germany, 3Indiana University of Pennsylvania, Indiana, PA, United States

There are strong correlations between cortical atrophy observed by MRI and clinical disability in multiple sclerosis. The objective of this study was to evaluate the progression of cortical atrophy over time in vivo in experimental autoimmune encephalomyelitis (EAE). Volumetric changes in the cerebral cortices of EAE mice were quantified by collecting in vivo MR images and morphometry. We observed that though atrophy progressed differently in each individual animal, all mice with EAE demonstrated significant cortical atrophy compared to normal controls. This is the first report of progressive cortical atrophy in vivo in a mouse model of MS.

2276.   Voxel-based morphometry using DARTEL in the mouse reveals differential impact of early and late prenatal inflammation on adult brain. 
Charlton Cheung1, Qi Li2,3, Edward X. Wu2,4, and Grainne Mary McAlonan5,6
1Psychiatry, University of Hong Kong, Pokfulam, Hong Kong, 2University of Hong Kong, Hong Kong, 3Centre for Reproduction, Development and Growth, 44Laboratory of Biomedical Imaging and Signal Processing, 5University of Hong Kong, Hong Kong, Hong Kong, 6State Key Laboratory for Brain and Cognitive Sciences

Mice exposed to maternal inflammation during prenatal life are used model aspects of neurodevelopmental disorders such as schizophrenia and autism. We used DARTEL to process images from 7T scanner and compare brain morphology in adult mice exposed to prenatal inflammation in early and late gestation with controls. Regional volumes in hippocampal-striatal regions were lower and lateral ventricular volume greater in mice exposed early in gestation compared to controls. In late exposed, volumes were lower in cerebellum, hippocampus, lateral ventricles and 4th ventricles larger. Time of exposure determines neuroanatomical outcome of prenatal inflammation and may be relevant to schizophrenia and autism.

2277.   Axonal Damage Caused by Exposure of Axon Terminals to Amyloid Beta 
David Carrick1, Bruce Campbell2, Hsiao-Fang Liang3, Wei-Xing Shi4, and Shu-Wei Sun5
1Basic Science, School of Medicine, Loma Linda University, Loma Linda, CA, United States, 2Clinical Laboratory Science, School of Allied Health, Loma Linda University, Loma Linda, 3Biophysics and Bioengineering, Loma Linda University, 4Pharmaceutical Sciences and Basic Sciences, Schools of Pharmacy and Medicine, Loma Linda University, 5Biophysics and Bioengineering, Loma Linda University, Loma Linda, CA, United States

Amyloid Beta peptides were injected into the right optic tract terminals region of mice. DTI was performed in 1 and 3 months after Amyloid Beta injection. Axonal damage was revealed as a 15% decrease of axial diffusivity found in the ipsilateral optic tracts and a 10% decrease of mean diffusivity in contralateral optic nerves. This study demonstrated the axonal degeneration induced by the exposure of axonal terminal sites to the Amyloid Beta.

2278.   Longitudinal MRI study to monitor brain changes of rTg4510 mice related tauopathy suppressed with/without Doxycycline 
Dewen Yang1, Zhiyong Xie1, David Caouette2, Carol Hicks2, Anthony Millici2, and David Raunig3
1BioImaging COE, Pfizer Worldwide Research & Development, Groton, CT, United States, 2Neuroscience RU, 3Neuroscience Research Statistics

Previous published paper demonstrated that the mutant tau in transgenic rTg4510 mice could be suppressed by Doxycycline. We designed a longitudinal MRI study to follow up brain volume changes to investigate the effect of Doxycycline in rTg4510 mice brain. A significant genotype effect (rTg4510 vs wt) was observed with the lateral ventricle volume (p< 0.0001). The lateral ventricle volume correlated well with the degree of hyperphosphorylated Tau staining. The increased lateral ventricle volume was early indicator for Tauopathy progression.

2279.   Does decompression sickness lead to brain injuries? 
Marius Widerøe1, Marianne Havnes2, Andreas Møllerløkken2, Alf Brubakk2, and Marte Thuen2
1Dep of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway, 2Dep of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway

Decompression sickness can cause neurological damage. We have investigated the brain of decompressed rats using extensive MR protocols including T2-maps, T2*-maps, manganese-enhanced MRI, dynamic enhanced MRI and DTI at several time points after decompression: 1 hour, 1 week and 2 weeks. No differences between groups was found on T2, T2*, MEMRI or DTI. DCE-MRI showed increased relative signal intensity and area under the dce-curve, indicating disruption of the blood-brain barrier. Thus, severe decompression does not seem to cause any structural or cellular injury to the brain tissue, but may cause changes in brain perfusion and integrity of the blood-brain barrier.

2280.   The Effect of the Ketogenic Diet on Neuroinflammation in an EAE Mouse Model of Multiple Sclerosis 
Gregory H Turner1, Do-Young Kim1, Junwei Hao1, Ruolan Liu1, Jong M Rho1, and Fu-Dong Shi1
1Barrow Neurological Institute, Phoenix, AZ, United States

Dietary treatments have become increasingly used as an alternative therapy to address a variety of neurological disorders. The ketogenic diet (KD) has been shown to promise in both translational studies and in the clinic. For this study the effects of the KD on an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis was investigated. In vivo MRI and bioluminescence imaging were used to examine lesion development and measure reactive oxygen species (ROS) in EAE mice given the KD. These studies revealed that the KD yields a reduction of the inflammatory response in an EAE model of multiple sclerosis.

2281.   In Vivo Pathological Mapping of the Rat Brain Infected with Angiostrongylus Cantonensis using MRI 
Ling-Yuh Shyu1, Hao-Hung Tsai2,3, Shin-Tai Chong2, Tzu-Hua Lee2, Kwong-Chung Tung4, and Jun-Cheng Weng2,3
1Department of Parasitology, Chung Shan Medical University, Taichung, Taiwan, 2School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan,3Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, 4Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan

Angiostrongylus cantonensis (A. cantonensis) is the most common cause of eosinophilic meningoencephalitis in Taiwan. This parasitic infection is endemic in the Southeast Asian and Pacific region, but it becomes a global infection in recent years. The infection in the final host, rats, or non-permissive host, including human, is acquired by ingesting contaminated raw snails. The third-stage larvae migrate to the brain and develop into the fifth stage with twice molts. The worms then migrate to lung and heart and develop into adult. The typical clinical presentation is acute eosinophilic meningoencephalitis frequently accompanied by brain and spinal cord disorders, and other symptoms of central nervous system (CNS). The features of the pathological changes in the brain were previously limited to a few case reports and techniques. Previously the diagnosis was established by immunodiagnosis, lumbar puncture and eosinophilia examination. Fourth- or fifth-stage larvae could be found in the cerebrospinal fluid (CSF) with lumbar puncture. Improper puncture and false immune response resulted in an erroneous diagnosis. Therefore, the purpose of this study was to determine the lesion localization, pathological changes and angiostrongyliasis characterization of rat brain infected with larvae of A. cantonensis by magnetic resonance imaging (MRI) techniques. The results were verified with histopathological study. Rats were infected with different numbers of A. cantonensis larvae and their brains were diagnosed continuously with MRI and histopathological study. The association between the clinical features of the rats and MRI findings was also addressed.

2282.   MRI Studies of Neuroprotection in a Mouse Model of Radiation Necrosis 
Xiaoyu Jiang1, John A Engelbach2, Dinesh K Thotala3, Robert E Drzymala3, Dennis E Hallahan3, Joel R Garbow4, and Joseph JH Ackerman4
1Department of Chemistry, Washington University in St. louis, st. louis, missouri, United States, 2Washington University in St. louis, 3Department of Radiation Oncology, Washington University School of Medicine, 4Department of Radiology, Washington University School of Medicine

Radiation necrosis is a severe, but late occurring type of injury to normal tissue, within and surrounding a radiation treatment field. Recently, an innovative mouse model of radiation necrosis was developed in our laboratory that displays all of the classic histologic signatures of necrosis seen in patients. This model can serve as a robust platform for studies aimed at providing a detailed characterization of radiation necrosis. Here, we use small-animal MRI to demonstrate the efficacy of an inhibitor of the serine/threonine kinase GSK-3lower case Greek beta as a neuroprotectant against radiation necrosis in irradiated mouse brain.

2283.   Anatomical phenotyping of the PML knockout mouse 
Benjamin Sinclair1,2, Jon Cleary2, Joanne Henderson3, Marc Modat1, Francesca Norris2,4, Paolo Salomoni3, Sebastien Ourselin1, and Mark Lythgoe2
1Centre for Medical Image Computing, UCL, London, United Kingdom, 2Centre for Advanced Biomedical Imaging, UCL, London, United Kingdom, 3UCL Cancer Institute, London, United Kingdom,4Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX)

This study applies MRI and image processing techniques to a mouse model with a knockout of the PML gene, which has known links with tumour suppression and neurogenisis.

2284.   Early metabolic changes in the amyotrophic lateral sclerosis SOD1 mouse brain are revealed using 1H MRS rather than CASL and 18FDG PET 
Hongxia Lei1,2, Elisabeth Dirren3, Carol Poitry-Yamate1, Bernard L Schneider3, Patrick Aebischer3, and Rolf Gruetter1,4
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Radiology, Univeristy of Lausanne, Lausanne, Switzerland, 3Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 4Radiology, University of Geneva, Geneva, Switzerland

Multimodal and non-invasive studies of SOD1 mouse brain allow following metabolic changes longitudinally in G93A SOD1 mice, an animal model mimicking human ALS. Metabolic changes are observed at two different time-points -- before and after apparition of the symptoms -- suggesting that 1H MRS is an effective strategy towards identifying potential biomarkers of ALS during the early post-symptomatic phase.

2285.   Rates of change of 1H and 31P MRS cerebral metabolites vs Lactate/NAA in the 48h following global transient global hypoxia-ischaemia in the newborn piglet 
Nicola Jayne Robertson1, Stuart Faulkner1, Alan Bainbridge2, Manigandan Chandrasekaran1, Dorottya Kelen1, Sudhin Thayyil1, Ernest Cady2, Xavier Golay3, and Gennadij Raivich1
1Institute for Women's Health, University College London, London, United Kingdom, 2Medical Physics and Bioengineering, University College Hospitals, London, United Kingdom, 3UCL Institute of Neurology, London, United Kingdom

1H MRS lactate/NAA is the most sensitive and specific MR biomarker of outcome following perinatal asphyxia in babies. In this validated large animal model of perinatal asphyxia we compared the rates of change of different 1H and 31P metabolite peak area ratios vs lactate/NAA during the 48 hours after a global transient hypoxic-ischaemic insult. Compared to Lac/NAA, Lac/Cr changed most rapidly and was most sensitive to lower degrees of injury while NAA/Cr, NTP/EPP and pHi/EPP were least sensitive to injury and responded last. Lac/NAA appears to provide sufficient sensitivity detect moderate to severe brain injury following global hypoxia-ischaemia.

2286.   Acute hypoglycemia induces increased brain lactate uptake and metabolism in rats. 
Henk M. De Feyter1, Kevin L. Behar2, Robin A. de Graaf3, and Douglas L. Rothman3,4
1Diagnostic Radiology, Yale University, New Haven, CT, United States, 2Department of Psychiatry, Yale University, 3Diagnostic Radiology, Yale University, 4Department of Biomedical Engineering, Yale University

Increased blood-to-brain transport of monocarboxylic acids (MCA's) by monocarboxylate transporter 1 (MCT1), has been suggested as an adaptation contributing to hypoglycemia unawareness. Lactate is the MCA with the highest concentration present during hypoglycemia. We investigated the role of blood lactate as alternative fuel during hypoglycemia by studying brain lactate transport and metabolism in healthy rats during hyperinsulinemic euglycemia and acute hypoglycemia using in vivo 1H-[13C] magnetic resonance spectroscopy (MRS) combined with [3-13C]-lactate infusion. The in vivo MRS data presented indicate actively regulated lactate transport over the blood-brain barrier responsive to plasma glucose levels.

2287.   Multiparametric MR assays of Spinocerebellar Ataxia 17 Transgenic Mice 
Chiao-Chi V Chen1,2, Zhi-Xuan Kuo1,2, Hsiu-Mei Hsieh3, and Chen Chang1,2
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, 2Functional and Micro-magnetic Resonance Imaging Center, Academic Sinica, Taipei, Taiwan, 3Department of Life Science, National Taiwan Normal University, Taipei, Taiwan

Spinocerebellar ataxia (SCA) 17 is a rare neurodegenerative disorder caused by an expanded polyglutamine in the TATA-binding protein (TBP). Little is known about the underlying neuroanatomical abnormalities. To better understand SCA 17, in this study, multiparametric MR assays were carried out using T2-weighted imaging based volumetric analysis, diffusion tensor imaging, and magnetic resonance spectroscopy in SCA 17 transgenic mice. The results indicate that shrunk size, increased diffusivity, and decreased NAA levels of the cerebellum surrounded by enlarged ventricular spaces characterize the TG mice of the SCA 17 human disease. These indications reveal the importance of cerebellar cell loss in SCA17.

2288.   Longitudinal study of neurochemical changes in Q140 mouse model of Huntington’s disease 
Ivan Tkac1, Lori Zacharoff2, and Janet M Dubinsky2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Department of Neuroscience, University of Minnesota

In vivo 1H NMR spectroscopy at 9.4T was used to investigate the neurochemical changes in the striatum and cerebral cortex of the Q140 knock-in mouse model of Huntington’s disease (HD). Mice were scanned repeatedly during the their lifespan (6 weeks – 24 months). More than 300 spectra were acquired. Most significant changes were observed for Gln, PCr, PE and Lac and were mostly localized in mouse striatum, which more closely mimic symptoms found in HD human patients.

2289.   Optimal therapeutic hypothermia temperature following perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet. 
Nicola Jayne Robertson1, Stuart Faulkner1, Manigandan Chandrasekaran1, Alan Bainbridge2, David Price2, Dorottya Kelen1, Aron Kerenyi1, Sudhin Thayyil1, Elizabeth Powell1, Ernest Cady2, Gennadij Raivich1, and Xavier Golay3
1Institute for Women's Health, University College London, London, United Kingdom, 2Medical Physics and Bioengineering, University College Hospitals, London, United Kingdom, 3UCL Institute of Neurology, London, United Kingdom

Although therapeutic hypothermia is safe and effective for neonatal encephalopathy, 50% infants have adverse outcomes; clinical trials are exploring cooling to deeper temperatures for longer periods. We used our validated piglet model of perinatal asphyxia to assess the effect of cooling to 35oC, 33.5oC, and 30oC on 1H MRS-based biomarkers and immunohistochemical markers of cell death. Mild cooling (33.5oC and 35oC) was neuroprotective, but moderate cooling (30oC) led to increased cell death and raised Lac/Cr in the deep grey matter but not white matter / cortex. This confirms regional differences in optimal cooling temperatures and has importance for clinical protocols.

2290.   Relation between 1H and 31P MRS biomarkers and immunohistochemical markers of cell death and inflammation in a perinatal asphyxia piglet model 
Nicola Jayne Robertson1, Manigandan Chandrasekaran1, Stuart Faulkner1, Alan Bainbridge2, Dorottya Kelen1, Sudhin Thayyil1, Ernest Cady1, Xavier Golay3, and Gennadij Raivich1
1Institute for Women's Health, University College London, London, United Kingdom, 2Medical Physics and Bioengineering, University College Hospitals, London, United Kingdom, 3UCL Institute of Neurology, United Kingdom

1H MRS thalamic lactate/NAA is used as a bridging biomarker in pre-clinical studies and as a surrogate endpoint in phase II perinatal asphyxia neuroprotection trials. We assessed the relation between 1H and 31P MRS biomarkers and immunohistochemical markers of cell death and neuroinflammation in our piglet perinatal asphyxia model. Lac/NAA showed a particularly strong positive correlation with TUNEL+ nuclei averaged across the forebrain at 48h (R2= 0.57). Other metabolite correlations were Pi/EPP (R2= 0.52), Lac/Cr (R2=0.50), NAA/Cr (R2=0.49), NTP/EPP (R2=0.36), PCr/EPP (R2=0.32), pHi (R2 = 0.14). Microglial ramification was particularly correlated with NTP/EPP (R2=0.40) and less with Lac/NAA (R2= 0.24).

2291.   In vivo9.4T 1H MRS for evaluation of brain metabolic changes in the Ts65Dn mouse model of Down syndrom 
Jean-Claude Beloeil1, William Même1, Nadir Yousfi1, Patricia Lospez-Pereira2, yann Hérault2,3, and Sandra Même1
1CBM CNRS UPR4301, orléans, France, 2TAAM CNRS UPS44, orléans, France, 3IGBMC, strasbourg, France

Down Syndrom (DS) is a genetic pathology caused by human chromosome 21 trisomy. It is characterized by a combination of comportemental, morphological or physiological alterations observable both in human and animal models. TS65Dn model is the most widely studied mice model for DS. It is interesting to explore cerebral metabolism of Ts65Dn models. In vivo Magnetic Resonance Spectroscopy (MRS) can provide information on brain metabolism and neuronal function. The aim of our study was to quantify changes in brain metabolites concentrations for TS65Dn mice compared to control mice with 9.4T 1H MRS.

2292.   Non-invasive magnetic resonance spectroscopy biomarkers of oxidative stress following traumatic brain injury 
William Miles Brooks1,2, Janna Harris3, Hung-Wen Yeh4, In-Young Choi1,5, and Sang-Pil Lee3,6
1Hoglund Brain Imaging Center, University of Kansas, Kansas City, KS, United States, 2Neurology, University of Kansas, Kansas City, KS, United States, 3Hoglund Brain Imaging Center, University of Kansas, Kansas City, KS, 4Biostatistics, University of Kansas, United States, 5Neurology, University of Kansas, 6Molecular & Integrative Physiology, University of Kansas

Traumatic brain injury (TBI) is a complex clinical entity. Oxidative stress is one pathological mechanism contributing to poor outcome and trials of anti-oxidant strategies are underway. However, no robust non-invasive biomarker of oxidative stress is available. Magnetic resonance spectroscopy provides non-invasive quantification of numerous neurochemicals, including anti-oxidants - glutathione (GSH) and vitamin C (ascorbate, Asc). We characterized the time course of GSH and Asc in an animal model of TBI. Since MRS is equally feasible in animal models and human survivors of TBI, MRS might provide a robust means for translating results from animals to patients.

2293.   Effects of Nitrones in Rodent Glioma Models assessed by 1H MR Spectroscopy 
Ting He1, Sabrina Doblas1, Debra Saunders1, Rebba Casteel1, Robert Floyd2, and Rheal Towner1
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 2Experimental Thearapeutics, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States

Gliomas are the most lethal adult primary brain tumors with a poor outcome. We evaluated the anti-tumor effects of nitrones PBN or OKN007 in several rodent glioma models (C6, RG2, and GL261) by assessing metabolite alterations with magnetic resonance spectroscopy (MRS). Pre-treatment of PBN or post-treatment of OKN007 was able to induce tumor regression and recover the metabolite changes induced by tumor growth to relatively normal levels in several gliomas. OKN007 was demonstrated to decrease angiogenesis and induce apoptosis in C6 gliomas. In conclusion, nitrones have anti-glioma effects and may be considered as potential therapeutics for human gliomas.

2294.   Does the Warburg effect exist in vivo? Analyzing glucose metabolism in FDG-PET-positive tumors by 13C-NMR spectroscopy 
Isaac Marin-Valencia1, Steve K Cho2, Levi B. Good2, Michael Long3, Xiankai Sun3, Juan M. Pascual2,4, Mark Jeffrey3, Elizabeth A Maher5, Craig R. Malloy3,5, Robert M. Bachoo2, and Ralph J. DeBerardinis1
1Pediatrics, UT Southwestern Medical Center, Dallas, Texas, United States, 2Neurology, UT Southwestern Medical Center, Dallas, Texas, United States, 3Radiology, UT Southwestern Medical Center, Dallas, Texas, United States, 4Physiology, UT Southwestern Medical Center, Dallas, Texas, United States, 5Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States

In vitro studies in tumor cells demonstrate that anaerobic glycolysis is active and oxidative pathways in the mitochondria are suppressed. We used a novel mouse model of glioblastoma to characterize glucose metabolism in the tumor and surrounding brain in vivo by 13C-NMR. The 13C spectra were similar between both tissues, showing an active CAC and differing only by an increased glutamine:glutamate ratio within the gliomas. The data reveal that tumor metabolism is more complex than classical models suggest, and that novel targets for therapy may be exposed by probing tumor metabolism with stable isotopes.

2295.   Stress during gestation and exposure to an indirect cannabinoid agonist during adolescence alter brain metabolism in mice 
Rossella Canese1, Simone Macrì1, Chiara Ceci1, Emiliano Surrentino1, and Giovanni Laviola1
1Cell Biology and Neurosciences Dept., Istituto Superiore di Sanità, Rome, RM, Italy

Stress during gestation and access to cannabinoid compounds during adolescence regulate emotional responses in adulthood, potentially favouring the onset of emotional disturbances. Here we investigated such prenatal-peripubertal interaction in rodents by exposing pregnant mice to corticosterone in drinking water and their adolescent offspring to an indirect cannabinoid agonist (URB597). The consequences of these treatments were studied in adult offspring by in vivo 1H MRS and behavioural testing. Both factors persistently alter adult brain metabolism and anxiety-like behaviour. These results may inform research on the interaction between early stress and adolescent access to psychotropic drugs in the onset of emotional disturbances.

2296.   Alternative Pathways of Glucose Metabolism in a Mouse Model of Human Brain Tumors 
Isaac Marin-Valencia1, Steve K. Cho2, Levi B Good2, Ashish Jindal3, Juan M. Pascual2,4, Ralph J. DeBerardinis1, Robert M. Bachoo2, Elizabeth A. Maher5, and Craig R. Malloy3,6
1Pediatrics, UT Southwestern Medical Center, Dallas, Texas, United States, 2Neurology, UT Southwestern Medical Center, Dallas, Texas, United States, 3Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, 4Physiology, UT Southwestern Medical Center, Dallas, Texas, United States, 5Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States, 6Radiology, UT Southwestern Medical Center, Dallas, Texas, United States

Increased flux through the pentose phosphate pathway (PPP) is required to support the high metabolic demands of cancer. Using an orthotopic murine model of glioblastoma (GBM) and renal cell carcinoma (RCC) metastatic to the brain, we compared the relative activity of PPP vs. glycolysis in both tumors and their respective surrounding brains using [1,2-13C2]glucose. The ratio of [3-13C]lactate/[2,3-13C2]lactate ratio was similar between tumors and surrounding brains, suggesting that much of the lactate in both tumors exchanges slowly with glycolytic intermediates or that the flux into PPP increases in proportion to glycolysis.

2297.   ASL-MRI Measurement of Cerebral Blood Flow following Experimental Traumatic Brain Injury and the Role of Human Alower case Greek beta 
Lesley M Foley1, Eric E Abrahamson2, T Kevin Hitchens1,3, Chien Ho1,3, William R Paljug2, John A Melick4, Patrick M Kochanek4,5, and Milos D Ikonomovic2
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, 2Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, 3Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States, 4Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, 5Departments of Critical Care Medicine, Pediatrics and Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Amyloid precursor protein and its toxic metabolite amyloid-ƒÒ (AƒÒ) increase after TBI. It is unknown whether increases in AƒÒ after TBI contributes to changes in brain hemodynamics. We used ASL-MRI to evaluate regional cerebral blood flow (CBF) in wild type C57BL/6 and APPNLh/NLh/C57BL/6 mice that express the human AƒÒ (hAƒÒ) peptide. Both at 72 hr and 3 weeks after injury, CBF deficits were significantly greater in APPNLh/NLh/C57BL/6 mice. Increased hAƒÒ concentrations may contribute to impaired hemodynamics and prolonged deficits in recovery of perfusion, supporting the idea that TBI is a risk factor for developing Alzheimer¡¦s disease later in life.

2298.   Increased Cerebrovascular Complications of Diabetic Mice-A Magnetic Resonance Imaging Study 
Qiang Shen1,2, Eric Muir1, Edward S Hui1, Rene C Rentería3, and Timothy Q Duong1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, 2Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, 3Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Diabetic cardiovascular or cerebrovascular complications are the major death cause of patients with diabetes mellitus. Diminished basal cerebral blood flow (CBF) and impaired cerebral vasodilatory response are two of cerebrovascular complications, but whether diabetes affects basal CBF is controversial. In this study, we investigated these two factors of cerebrovascular complications using the Akita mouse model of diabetes. Quantitative basal CBF and CBF changes during hypercapnic challenge were measured. Global basal CBF was lower in diabetic mice (Akita) compared to age-matched controls. Diabetic mice also had attenuated vasodilatory response to hypercapnic challenge.

2299.   Resting-state fMRI and pharmacological MRI of changing dopaminergic activity in the developing rat brain 
Kajo van der Marel1, Liesbeth Reneman2, and Rick M. Dijkhuizen1
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Radiology, Academical Medical Center, Amsterdam, Netherlands

Early dopaminergic dysfunction during sensitive periods of brain development has been associated with altered corticostriatal processing, which is implicated in neuropsychiatric conditions such as ADHD and schizophrenia. Neuroimaging has revealed age-dependent responses to dopaminergic psychostimulation. To study the effects of brain development on baseline corticostriatal function, we applied resting-state fMRI functional connectivity (RSFC) analysis and pharmacological MRI (phMRI) in adolescent and adult rats. PhMRI confirmed lower D-amphetamine evoked responses during adolescence, while RSFC revealed increased neural synchrony between bilateral caudate-putamen in adults. This demonstrates that combined phMRI and RSFC may provide complementary insights into the ontogeny of brain dopamine systems.

2300.   In Vivo Characterization of Developing Rabbit Brain with Diffusion Tensor MRI and Tractography 
Yi-Wen Peng1, Yong-Jheng Wun2, Cheng-Hung Lai1, and Jun-Cheng Weng2,3
1Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, 2School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan,3Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

The brain is extraordinarily complex, and yet its origin is a simple tubular structure. Characterizing its anatomy at different stages of brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. Diffusion tensor imaging (DTI), a non-invasive method of magnetic resonance imaging (MRI), is sensitive to structural ordering in brain tissue particularly in the white matter tracts. Diffusion anisotropy changes with demyelinating diseases and also with neural development. In the animal studies, however, only ex vivo brains have been studied. Therefore, the goal of this study was to study developmental changes in regional diffusion anisotropy and white matter fiber tract maturation of in vivo rabbit brains. In this study, DTI data of in vivo rabbit brains (4 weeks to 24 weeks) were acquired and analyzed. Normalized trace apparent diffusion coefficient (ADC), generalized fractional anisotropy (GFA), R2 mapping and fiber tracts were generated and compared across the ages. Our results showed that color maps of diffusion indices, R2 mapping, and 3D tractography revealed that important white matter tracts, such as the olfactory tract, corpus callosum and hippocampus, become apparent during mature period. Regional DTI tractography of the white matter tracts showed refinement in regional tract architecture with maturation. The white matter anisotropy and R2 values increased with age, and the diffusion coefficient decreased with age.

2301.   Diffusion tensor imaging for evaluation of radiation-induced developmental abnormalities in the white matter 
Shigeyoshi Saito1, Tsuneo Saga1, and Ichio Aoki1
1Molecular Imaging Center (MIC), National Institute of Radiological Sciences (NIRS), Chiba, Chiba, Japan

Prenatal radiation exposure can induce various kinds of central nervous system (CNS) disorders, such as white matter alterations. In this study, we evaluated the developmental white matter disorder induced by prenatal X-ray exposure using diffusion tensor imaging. Fractional anisotropy (FA) maps calculated from the diffusion tensor images were compared to a histological study of myelination staining (LFB, Luxol fast blue). We found that FA maps from diffusion tensor imaging enabled noninvasive evaluation of the disturbance in myelination apparent in radiation-exposed rats. This study provides useful information for biomedical assessment of radiation-induced developmental abnormalities in the white matter.

2302.   Diffusion Abnormality in Olfactory Bulbs of Type-I Diabetic Rats 
Li feng Gao1, Ming ming Huang1, and Hao Lei1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics & Mathematics, The Chinese Academy of Science, Wuhan, China, People's Republic of

Previous clinically diabetes mellitus studies have found hyperglycemia often develop olfactory dysfunction. In this study, diffusion tensor imaging is used to assess axonal diffusion abnormalities in the olfactory system in type-I diabetic rats at 2 weeks after streptozotocin injections. Compared to the control animals, the diabetic rats had significantly reduced fractional anisotropy, increased mean appear diffusion coefficient and radial diffusivity in the olfactory bulb. The result suggests in the early stage of diabetes (2w), the pathological change has developed rapidly in the rat olfactory bulb.

2303.   Monitoring Myelination by Transplanted Oligodendrocyte Precursors in Dysmyelinated Mice with MT and DT Imaging 
Piotr Walczak1,2, Jiangyang Zhang1, Galit Pelled1,3, Segun Bernard1,2, Shashikala Galpoththawela1,2, James T Campanelli4, and Jeff WM Bulte1,2
1Russel H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University, Baltimore, MD, United States, 2Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, 3F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Q Therapeutics, Inc., Salt Lake City, UT, United States

Cell-based therapy of neurological disorders such as congenital dysmyelination has shown considerable potential for clinical translation. The implementation of imaging techniques is crucial to expedite progress in this field. Magnetization transfer and diffusion tensor (DT) imaging were used for monitoring of myelination by glial restricted progenitors (hGRP) transplanted into myelin-deficient mice. Serial MRI data showed a significant increase in fractional anisotropy (FA) in the corpus callosum but no significant changes in the magnetization transfer ratio. Histology confirmed expression of myelin-specific proteins nearby transplanted hGRPs. This indicates that DT imaging is more sensitive tool to interrogate myelinating potential of transplanted hGRPs.

2304.   Mouse Embryo Phenotyping with Contrast-enhanced micro-Diffusion Tensor Imaging 
Bernard M Siow*1,2, Jon O Cleary*1,3, Nicholas D Greene4, Pankaj Daga3, Marc Modat2, Roger J Ordidge3, Sebastien Ourselin2, Daniel Alexander2, and Mark F Lythgoe1
1Centre for Advanced Biomedical Imaging, Department of Medicine and Institute of Child Health, UCL, London, United Kingdom, 2Centre for Medical Image Computing, UCL, London, United Kingdom, 3Department of Medical Physics and Bioengineering, UCL, London, United Kingdom, 4Neural Development Unit, Institute of Child Health, UCL, London, * Equal Contribution

Morphological phenotyping of mouse embryos is still heavily reliant on histological sectioning: a destructive process that is time-consuming and operator dependent. Diffusion-tensor imaging (DTI) is a powerful technique that can explore tissue structure non-invasively, providing microstructural information such as the direction of tissue fibres. We have developed a Gd-DTPA contrast-enhanced protocol for whole-body DTI of mid-gestation embryos, comparing embryo preparation, pulse sequences and resolution. This protocol has been applied to wild-type and splotch mouse model of spina bifida embryos at 15.5 dpc. We have shown that whole-body µDTI is able to delineate a number of anatomical brain regions that are not apparent on T1 weighted µMRI images.

2305.   Using structural MRI and DTI to map plastic changes in the mouse brain resulting from deep brain stimulation 
M. Mallar Chakravarty1,2, Clement Hamani3,4, Jacob Ellegood1, Mustansir Diwan3, Christine Laliberté1, Jonathon Bishop1, Jun Dazai1, Brian J Nieman1, Jose N Nobrega3, R Mark Henkelman1, and Jason P Lerch1
1Mouse Imaging Centre (MICe), The Hospital for Sick Children, Toronto, Ontario, Canada, 2Rotman Research Institute, Baycrest, Toronto, Ontario, Canada, 3Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada, 4Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada

Deep brain stimulation, a surgical procedure where a stimulating electrode is implanted in the brain, has long been used to alleviate symptoms of Parkinson’s disease. Researchers are currently researching new targets in the context of different neurological dysfunctions. Here we investigate the efficacy of stimulating the anterior cingulate in the context of treatment resistant depression. We used voxel wise anatomical analyses of high-resolution T2-weighted and diffusion weighted images from 24 mice (8 wild type, 8 sham lesion, 8 DBS) to examine plastic changes in reponse to DBS of the anterior cingulate. Results demonstrate volumetric expansion of the hippocampus and local decreases in mean diffusivity in response to DBS.

2306.   Bilateral Enucleation Before and After the Critical Period for the Specification of Interhemispheric Axonal Connectivity Induces Similar Changes on White Matter Fractional Anisotropy 
Christopher D. Kroenke1, Jaime F. Olavarria2, Andrew S. Bock2, Erin N. Taber1, and Byung Park1
1Oregon Health & Science University, Portland, OR, United States, 2University of Washington, Seattle, WA, United States

An animal model has been developed to investigate the relationship between axonal connectivity and water diffusion fractional anisotropy (FA) in white matter (WM). Binocular enucleation, a form of visual deprivation, prior to the critical period for the specification of interhemispheric axonal connectivity produces abnormal connectivity patterns in mature ferrets. Correspondingly, WM FA within early-enucleated ferrets is lower than normally-sighted control animals. Enucleation subsequent to the critical period results in normal connectivity patterns. However we, find abnormal WM FA within late-enucleated ferrets resembling that of early-enucleates. This suggests reduced WM FA arises from microstructural-level changes rather than abnormal to axonal connectivity.

2307.   Superoxide dismutase overexpression improves FA and ADC in the brains of a mouse model of Alzheimer's Disease 
Brittany R. Bitner1,2, Taeko Inoue1, Lingyun Hu1, Chi An Chiang3, and Robia G Pautler1,2
1Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States, 2Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States, 3Neuroscience, Baylor College of Medicine

Alzheimer’s disease (AD) is the most common form of age-related dementia. Previous studies have shown that the overexpression of the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD) in a mouse model of AD (Tg2576) can reduce pathological findings. To determine whether SOD overexpression in Tg2576 AD mice (SOD/AD) can recover structural changes, we imaged aged SOD/AD mice and their littermates (AD, SOD, and wildtype) using diffusion tensor imaging. We found that AD mice had significant deficits in their fractional anisotropy and apparent diffusion coefficient compared to controls in several brain regions while SOD/AD mice exhibited significant recovery.

2308.   In-Vivo Mouse Brain DT-MRI: Assessment of Gender Specific Response to the Thyroid Hormone Remyelinating Treatment 
Laura-Adela Harsan1, Alexandru Parlog1, Neele Hübner1, Jürgen Hennig1, and Dominik von Elverfeldt1
1Department of Radiology, Medical Physics, University Hospital Center, Freiburg, Germany

In the present study we comparatively investigated by quantitative DT-MRI, the response of the cuprizone demyelinated male and female mice to a remyelinating therapy based on thyroid hormones. Increased radial diffusivity in the white matter of cuprizone mice was associated with myelin loss and axonal injury. Three weeks of daily injections with T3, gradually restored the myelin layers and induced recovery in both genders. A certain trend of faster and more consistent remyelination was observed in the female mice. The results are valuable for understanding the role of gender in the physiopathology and regeneration of the brain white matter.

2309.   Correlation between DTI and Visual Evoked Potential in Mice with Optic Neuritis 
Dan Xu1, Hsiao-Fang Liang2, Wei-Xing Shi3, and Shu-Wei Sun4
1Pharmaceutical Sciences and Basic Sciences, Schools of Pharmacy and Medicine, Loma Linda University, Loma Linda, CA, United States, 2Biophysics and Bioengineering, Loma Linda University,3Pharmaceutical Sciences and Basic Sciences, Schools of Pharmacy and Medicine, Loma Linda University, 4Biophysics and Bioengineering, Loma Linda University, Loma Linda, CA, United States

Diffusion tensor imaging (DTI) and visual evoked potential (VEP) recording were performed in mice with chronic experimental autoimmune encephalomyelitis (EAE), an animal model of optic neuritis. Correlation analysis showed that VEP amplitudes were significantly correlated with DTI indices of the optic nerves and optic tracts, providing the evidence that microstructural changes detected by DTI are associated with functional alteration.

2310.   lower case Greek alpha7 Nicotinic Receptor Mediation of CNS Inflammatory Response Examined by Magnetic Resonance Imaging and Bioluminescence Imaging 
Gregory H Turner1, Junwei Hao2,3, Alain R Simard4, Jie Wu2, Paul Whiteaker4, Ronald J Lukas4, and Fu-Dong Shi2
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, 2Neurology, Barrow Neurological Institute, Phoenix, AZ, United States, 3School of Medicine, Nankai University, Tianjin, China, People's Republic of, 4Neurobiology, Barrow Neurological Institute, Phoenix, AZ, United States

Nicotinic acetylcholine receptors (nAChRs) play critical roles throughout the brain and body by mediating cholinergic excitatory neurotransmission, modulating neurotransmitter release, and effecting gene expression and cellular interactions. Studies have shown that many immune cell types express nAChR subunits and that binding of nicotine or acetylcholine to α7-nAChR leads to a suppression of inflammation. This study used a combination of in vivo MRI and bioluminescence imaging to examine the effect of nicotine on EAE in an α7-nAChR knockout mouse. The results of this study indicate that cholinergic modulation of inflammation involves not only α7-nAChR but also likely involves several nAChR subtypes.

2311.   The Evolution of Traumatic Brain Injury in a Rat Model: Implications for Cell Tracking with MRI 
L Christine Turtzo1,2, Matthew D Budde1,2, Eric M Gold1,2, Bobbi K Lewis1, Lindsay E Janes1,2, William D Watson2,3, and Joseph A Frank1,2
1Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD, United States, 2Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, 3Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

The natural evolution of experimental traumatic brain injury is not fully characterized in the literature. The primary motor cortex of female Wistar rats was targeted with controlled cortical impact, and lesion evolution was monitored by serial MRI. Injuries that initially appeared similar on early MRI could be markedly different by Day 30. A high degree of hemorrhagic transformation of lesions was observed between days 2 and 9. The evolution of hemorrhage may complicate the interpretation of MRI cell tracking studies utilizing iron-labeled cells.

2312.   Tracking of Neuroprogenitor Cells in Association with Traumatic Brain Injury 
Jens Rosenberg1,2, Ali Darkazalli3, Cathy W. Levenson3, and Samuel Colles Grant1,2
1National High Magnetic Field Laboratory, The Florida State University, Tallahassee, FL, United States, 2Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States, 3Biomedical Sciences, The Florida State University, Tallahassee, FL, United States

This study investigates if magnetically labeled neuroprogenitor cells (NPC) from the subventricular zone (SVZ) will deviate from migration along the rostral migratory stream (RMS) to address neuronal damage resulting from traumatic brain injury (TBI). Results indicate that TBI did not impact the cellular uptake of micron sized magnetic particles but potentially slowed migration along the RMS and re-routed NPCs and their progeny to damaged areas. The necrotic cores of TBI lesions show dark contrast in the periphery, which partially represent cells migrating from the SVZ to the TBI as part of either inflammatory response or regeneration in the lesion penumbra.

2313.   Use of Endothelial Progenitor Cells as Gene Carrier and Multimodal Imaging Probes 
Nadimpalli RS Varma1, ASM Iskander1, Adarsh Shankar1, Branislava Janic1, Kenneth Barton2, Meser M Ali1, Hamid Soltanian-Zadeh1, Quan Jiang3, and Ali Syed Arbab1
1Radiology, Henry Ford Hospital, Detroit, Michigan, United States, 2Radiation Oncology, Henry Ford Hospital, Detroit, Michigan, United States, 3Neurology, Henry Ford Hospital, Detroit, Michigan, United States

Endothelial progenitor cells (EPCs) were collected from human cord blood and genetically modified to carry sodium human iodide symporter (hNIS) gene. Transgenic and control EPCs were magnetically labeled and administered systemically or locally in human glioma bearing rats. Migration and expression of hNIS in glioma were monitored by MRI and Tc-99m SPECT imaging, respectively. Both MRI and Tc-99-SPECT were able to track the migration and accumulation of systemically and locally administered EPCs in glioma. Expression of hNIS was detected by Tc-99m activity. EPcs can be used as imaging probe and gene carrier.

2314.   Image-Guided Stereotactic Biopsy System for Small Animal Experiments 
Jonathan Douglas Plasencia1, Kevin M. Bennett1, Gregory H. Turner2,3, Leland S. Hu4, and David H. Frakes1,5
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States, 2Keller Center for Imaging Innovation, Phoenix, Arizona, United States, 3Barrow Neurological Institute, Phoenix, Arizona, United States, 4Department of Radiology, Mayo Clinic Arizona, Phoenix, Arizona, United States, 5School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, Arizona, United States

Advances in physiologic and molecular MRI-based techniques have greatly improved the capability to monitor in vivo the pathophysiologic behavior of pre-clinical small animal tumor models and their response to novel drug therapies. A critical part to confirming the accuracy of imaging techniques is the correlation of MRI measurements with tissue analysis parameters. We propose an economically viable mechanical-based image-guided stereotactic biopsy system for small animal experiments that achieves sub-millimeter needle tip positioning accuracy. Methods are described in detail and validation results are presented.

Traditional Posters : Neuroimaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Clinical Application of Diffusion Tensor Imaging

Monday May 9th
Exhibition Hall  14:00 - 16:00

2315.   Voxel Based Analysis of Motor Neurone Disease using Apparent Fibre Density 
David Raffelt1,2, Stephen Rose3, J-Donald Tournier4,5, Robert Henderson6, Stuart Crozier2, Olivier Salvado1, and Alan Connelly4,5
1The Australian E-Health Research Centre, CSIRO, Brisbane, QLD, Australia, 2Biomedical Engineering, School of ITEE, University of Queensland, Brisbane, QLD, Australia, 3Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia, 4Brain Research Institute, Florey Neuroscience Institutes (Austin), Melbourne, VIC, Australia, 5Department of Medicine, University of Melbourne, Melbourne, VIC, Australia, 6Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia

Motor Neurone Disease (MND) involves progressive degeneration of the motor neurons and is typically fatal within 2-5 years; consequently there is considerable need for neuroimaging biomarkers to aid prognosis and pharmaceutical development. In this work we demonstrate the use of a recently developed measure called Apparent Fibre Density (AFD) to detect differences in MND within pathways related to the motor cortex. In addition to corroborating previous findings in MND, this study demonstrates the clear advantage of using AFD analysis in the context of multiple fibre orientations, by identifying not only the location, but also the orientations along which differences exist.

2316.   White matter differences between bilinguals and monolinguals revealed by diffusion tensor imaging (DTI) 
Seyede Ghazal Mohades1,2, Esli Struys1, and Robert Luypaert2
1VUB, Brussels, Brussels, Belgium, 2MRI, UZ Brussel, Brussels, Brussels, Belgium

This study is aimed to find differences in the structure of white matter of the brain between monolinguals and bilinguals. MR-DTI based tractography is used to track three sets of fibers in the areas that are of interest in linguistic studies (i.e. betwwenBroca’s and Wernicke’s areas, between broca’s area and corpus callosum and from anterior midbody of corpus callosum to primary motor cortex ). The results show that there is significant difference in FA value of fibers connecting Broca’s to Wernicke’s area and also the fibers that connect Broca’s area to corpus callosum between these two groups.

2317.   A diffusion spectrum tractography study on fiber integrity of fornix and correlation with clinical symptoms in schizophrenia 
Jhih-Wei He1, C-M Liu2, H-G Hwu2, C-C Liu2, F-H Lin1, and W-Y I Tseng3
1Institute of Biomedical engineering, National Taiwan University, Taipei, Taiwan, 2Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, 3Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

To understand the relationship between anatomical changes and clinical syndromes in schizophrenia, we used diffusion spectrum imaging (DSI) to compare the general fractional anisotropy (GFA) of the fornix between patients and controls, and explored the correlations between GFA values and PANSS subscores. Significant reduction of GFA in bilateral fornix was found in patients. We also found positive correlations between GFA of right fornix and subscore P7 (Hostility), G8 (Uncooperativeness), and a negative correlation between left fornix and subscore G10 (Disorientation). Our findings demonstrate the usefulness of DSI tractography to investigate the functional relevance of the white matter tracts in schizophrenia.

2318.   Temporal behavior of diffusion tensor properties in ex vivo human brain hemispheres 
Robert J. Dawe1, Julie A Schneider2, David A Bennett2, and Konstantinos Arfanakis1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, 2Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Diffusion tensor imaging (DTI) of ex vivo human brain specimens offers a unique opportunity for histopathologic verification of in vivo DTI findings. However, DTI data acquired ex vivo may be contaminated by postmortem changes to the tissue’s MR properties. In this work, human brain hemispheres were imaged with DTI over time up to one month postmortem. Mean diffusivity underwent a drastic reduction within one day postmortem. Postmortem fractional anisotropy was initially similar to antemortem values, but decreased substantially within one week postmortem.

2319.   Abnormalities in the Microstructure of the Fronto-Striatal Fiber Pathways in Children with Attention-Deficit/Hyperactivity Disorder: Preliminary Results Using Diffusion Spectrum Imaging Tractography 
Yi-Huan Wu1, Yu-Chun Lo2, Shur-Fen Susan Gau3, and Wen-Yih Isaac Tseng4,5
1School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, 3Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, 4Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, 5Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

Attention deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed neurodevelopmental disorders in childhood. Deficits in neural circuits linking regions of the prefrontal cortex and the striatum (caudate nucleus and putamen) have been postulated to account for the core symptoms in ADHD. Using diffusion spectrum imaging, we found that children with ADHD had lower generalized fractional anisotropy of the fronto-striatal fibers compared with healthy children. This finding implies a disruption in the normal pattern of structural and functional connectivity in fronto-striatal brain regions in children with ADHD.

2320.   Evidence for structural abnormality in the optic radiations in children with Optic Nerve Hypoplasia 
say Ayala-Soriano1, Emma Webb2, Kiran Seunarine3, Ruth Lions4, Tessa Mellow4, Michelle O'Reilly5, WK Chong6, Mehul Dattani7, Alki Liasis4, and C A Clark3
1Imaging and Physics, Institute of Child health,Department of Neurosurgery, Great Ormond Street Hospital, London, UK, United Kingdom, 2Imaging and Physics,Institute of Child Health, United Kingdom, 3Imaging and Physics, Institute of Child Health, London, United Kingdom, 4Opthalmology, Great Ormond Street Hospital, London, United Kingdom, 5Neurosciences, Institute of Child Health, London, United Kingdom, 6Neuroradiology, Great Ormond Street Hospital, London, United Kingdom, 7Endocrinology, Great Ormond Street Hospital, London, United Kingdom

Optic nerve hypoplasia (ONH) is a congenital abnormality characterised by an underdevelopment of the optic nerve and is the third most common cause of severe visual impairment in children. ONH is a clinical diagnosis only and conventional MRI fails to detect all the cases. Eleven children with ONH aged 2 to 11 and 22 controls were enrolled in the study. TBSS analysis revealed that fractional anisotropy (FA) within the optic radiations was lower bilaterally in patients with ONH compared to controls (p < 0.05). TBSS analysis provided evidence for structural abnormality in the optic radiations in paediatric patients with ONH.

2321.   Investigating the Relationship Between the Disruption of Primary Sensorimotor Pathways and Hand Function in Congenital Hemiplegia: An MRI Structural Connectivity Study 
Stephen Rose1, Kerstin Pannek1, Andrea Guzzetta2, and Roslyn Boyd3
1Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia, 2Department of Developmental Neuroscience, Stella Maris Scientific Institute, Pisa, Italy, 3Queensland Cerebral Palsy and Rehabilitation Research Centre, University of Queensland, Brisbane, Queensland, Australia

Unilateral periventricular brain lesions occurring early during the third trimester of pregnancy are a significant cause of congenital hemiplegia. However, little is known regarding the role of sensorimotor pathways that project directly into the primary motor cortex in controlling paretic hand function. In this study, we introduce an automated structural connectivity approach for correlating asymmetry indices derived for the corticospinal tracts and spinothalamic-corticothalamic pathways with clinical measures of paretic hand function. Our findings support the concept that preservation of afferent sensorimotor thalamic pathways has more influence on motor function control of the paretic hand than preservation of corticospinal tracts.

2322.   Identification and interpretation of microstructural abnormalities in motor pathways in adolescents born preterm 
Samuel Groeschel1, J.-Donald Tournier2, Gemma Northam3, Torsten Baldeweg3, John Wyatt4, Brigitte Vollmer5,6, and Alan Connelly2
1Experimental Pediatric Neuroimaging and Developmental Medicine & Child Neurology, University Children's Hospital, Tuebingen, Germany, 2Brain Research Institute, Melbourne, Australia, 3UCL Institute of Child Health, London, United Kingdom, 4UCL Hospitals, London, United Kingdom, 5Karolinska Institute, Stockholm, Sweden, 6University of Southampton, United Kingdom

The objective of the present study is to investigate diffusion parameters along motor pathways in adolescents born preterm. HARDI data of 45 preterm adolescents and 31 term-born controls were analysed using Constrained Spherical Deconvolution and a probabilistic tracking algorithm. The major finding in this study is that disruption of WM microstructure in a single fibre region with resulting higher radial diffusivity leads to lower FA, whereas selective disruption of one fibre population in a crossing fibre region may lead to higher FA. These findings challenge the common simplistic interpretation of FA as a measure of WM tract integrity.

2323.   Robust subdivision of the thalamus in children based on probability-distribution-functions calculated from probabilistic tractography. 
Philip Julian Broser1, Faraneh Vargha-Khadem2, and Chris A. Clark3
1Imaging and Biophysics Unit, UCL Institute of Child Health, London, London, United Kingdom, 2Developmental Cognitive Neuroscience Unit, UCL Institute of Child Health, 3Imaging and Biophysics Unit, UCL Institute of Child Health, London, United Kingdom

In this study we developed a new method to analyze the thalamus and its constituent substructures based on probabilistic tractography. Probabilistic tractography is an MRI technique that estimates the likelihood of connection between two points in the brain by sampling the distribution of greatest diffusion directions in each voxel of the brain image. In contrast to the previously published methods, which are applied at the group level, our method can be used to analyze the thalamic substructures in individual datasets. The method was applied to a MRI data set of 43 healthy children. Using this data set and our method we compiled a standard map of the thalamic substructures and compared this with existing atlases. We envisage in future that this standard map and the proposed method will be useful for studies of thalamic damage, particularly in children, which can be applied in individual cases. This should make possible future studies of thalamic connectivity with correlation to neurological dysfunction.

2324.   Structural Plasticity in Stroke Inferred by Probabilistic Tractography & MEG 
Monica Bucci1, Kelly Westlake1, Christopher Nguyen1, Bagrat Amirbekian1, Srikantan Nagarajan1, and Roland G Henry1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States

Structural remodeling of white matter may occur in motor recovery after stroke. We mapped the structural connectivity of the network of hand motor function, by combining magneto-encephalography, with HARDI diffusion MRI, in 4 controls and 4 stroke subjects before and after a robotic rehabilitation intervention. In 4 control subjects we successfully mapped the structural connectivity of the motor network. When tracking in stroke patients we observed improved structural connectivity for the ipsilesional M1 connections to contralateral M1 and to the ipsilesional ventral PMC in the patient with the best recovery score and different degrees of structural changes in the others.

2325.   Diffusion Tensor Metrics Changes in the White Matter of Systemic Lupus Erythematosus Patients 
Maria Luisa Mandelli1, Monica Bucci1, Eduardo Caverzasi1, Mehul Sampat1, Grace Yoon2, Patricia P Katz2, Laura Julian2, and Roland G Henry1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Department of Medicine, UCSF, San Francisco, CA, United States

Systemic Lupus Erythematosus is an autoimmune disorder affecting the central (CNS) nervous system often occurring in the subcortical white matter. Diffusion Magnetic Resonance Imaging is an imaging tool of choice to detect subcortical white matter damage. The purpose of this study is to investigate whether Mean Diffusivity (MD), Fractional Anisotropy (FA), and eigenvalues in the white matter of the brain of Systemic Lupus Erythematosus (SLE) patients differ from those of healthy controls. SLE patients showed a significant decrease on FA (P=0.010) and on Axial Diffusivity (λ1) (P=0.017) measures compared to control subjects in the normal appearing white matter.

2326.   Role of diffusion-tensor imaging in post-cardiac arrest patients still comatose 3-days post-resuscitation 
Ona Wu1, Leonardo M Batista2, Thomas Benner1, A Gregory Sorensen1, Karen L Furie2, and David M. Greer2,3
1Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 2Department of Neurology, Massachusetts General Hospital, Boston, MA, United States, 3Department of Neurology, Yale University, New Haven, CT, United States

Cardiac arrest survivors who were still comatose 3 days post-resuscitation were analyzed to investigate the utility of diffusion tensor imaging in identifying patients with a good chance of long-term recovery, defined by 6-month modified Rankin Scale score <=4. Imaging studies performed more than 72 hours from resuscitation showed significant differences in terms of good and poor outcome. Studies performed earlier than 72 hours were inconclusive between patients with good and poor outcome. For patients who are still in a comatose state, late imaging can provide useful information regarding the patient’s chances for recovery.

2327.   Evaluation of fractional anisotropy and apparent diffusion coefficient of Broca's area in Parkinson's disease using diffusion tensor imaging 
Jung-Hoon Lee1,2, Sang-Young Kim1, Kyung-Bae Lee1,2, Do-Wan Lee1, Youn-Bong Choi2, and Bo-Young Choe1
1Department of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea, Republic of, 2Department of Radiology, Kyunghee University Medical Center, Seoul, Korea, Republic of

The purpose of this study was to determine if changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of Broca's and Wernicke's areas could be observed in patients with Parkinson's disease (PD) by diffusion tensor imaging (DTI). The FA values in Broca's and Wernicke's areas of patients with PD were significantly decreased compared to controls. In addition, fiber-tractography helped to visualize the connection of nerve fibers in language areas of the left hemisphere. These results suggest that neurodegenerative changes occur in the language areas of patients with PD.

2328.   Diffusion Tensor Imaging of Normal and Pathological Human Optic Nerves using 2D ss-IVIM-DWEPI and a Custom Designed 20-channel Phase Array Coil at 3T System. 
Seong-Eun Kim1, John Rose2, Ji Kang Park3, Eun-Kee Jeong1, John Rock Hadley1, Emilee S Minalga1, and Dennis L Parker1
1Utah Center for Advanced Imaging Research, Department of Radiology, University of Utah, Salt Lake City, Utah, United States, 2Department of Neurology, University of Utah, 3Department of Radiology, Jeju National University Hospital, Jeju, Korea, Republic of

DT parameters measured by DTI, such as FA enable more sensitive and specific detection and monitoring of structural changes caused by pathology such as edema and inflammation which occurs in acute optic neuritis. However, in vivo DTI of the optic nerve (ON) using the conventional 2Dsingleshot EPI is generally very challenging because of its small size and the presence of magnetic susceptibility artifacts. In this work we present the measurement of DT parameters such as mean diffusivity (MD), fraction anisotropy (FA), axial and radial diffusivities of normal and pathological ONs obtained with 2D ss-IMIV DWEPI and a dedicated 20-channel coil.

2329.   Structural brain differences between patients with non hepatic liver cirrhosis and HCV-patients without liver cirrhosis 
Peter Raab1, Kathrin S Blum1, Anita B Tryc2, Annemarie Goldbecker2, Ali Tabesh3, Heinrich Lanfermann1, and Karin Weißenborn2
1Neuroradiology, Hannover Medical School, Hannover, Germany, 2Neurology, Hannover Medical School, Hannover, Germany, 3Radiology, New York University, New York, United States

Neuropsychological impairments in liver disease often present as deficits in attention, memory and higher executive function. Different liver diseases like HCV infection as well as liver cirrhosis can lead to similar symptoms. Diffusion Kurtosis Imaging and 1H-MR-Spectroscopy were used to look for structural brain differences in these two types of liver disease, compared to normal data. The results for cirrhosis patients are consistent with increased water content due to the altered ammonia metabolism, whereas in HCV patients results indicate consistency with the idea of increased microglial activation in the basal ganglia due to the known brain invasion by the hepatitis-C-virus.

2330.   Anatomical Organization of the Blind's Brain: Combined VBM and DTI Analysis 
Zhi Wang1, William FC Baar¨¦2,3, Ron Kupers2, Tim Dyrby2, Olaf Paulson2, Min Chen1, Cheng Zhou1, and Maurice Ptito2
1Radiology, Beijing Hospital, Beijing, Beijing, China, People's Republic of, 2Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark, 3Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark

We extended further our previous results by exploring here the whole brain white matter organization in a large cohort of congenital blindness(CB) compared to normal sight controls(NS) by combining VBM-DARTEL and DTI. All components of the visual system were reduced, especially the bilateral superior colliculi. All structures belonging to the visual system showed significant reductions of anatomical connectivity. Eleven of thirteen NS showed the entire visual-related fiber tracts. On the contrary, only 2 of 13 CB demonstrated the similar fiber tracts.

2331.   White matter network abnormalities are associated with cognitive decline in chronic epilepsy 
Maarten Vaessen1,2, Jacobus Jansen1,2, Marielle Vlooswijk3, Paul Hofman1,2, Marian Majoie3,4, Albert Aldenkamp2,4, and Walter Backes1,2
1Radiology, Maastricht University Medical Centre, Maastricht, Netherlands, 2School for Mental Health and Neurosciences, Maastricht University, Maastricht, Netherlands, 3Neurology, Maastricht University Medical Centre, Maastricht, Netherlands, 4Epilepsy Centre Kempenhaeghe, Heeze, Netherlands

The relation between white matter connectivity abnormalities and cognitive decline in chronic epilepsy was investigated using graph theoretical network analysis on tractography derived volumetric structural network. Clustering and path lengths appeared abnormal in epilepsy patients with cognitive impairment and were strongly correlated with IQ and IQ discrepancy scores. These results suggest that epilepsy interferes with structural networks that play a role in cognitive impairment.

2332.   Diagnostic prediction of language impairment in Autism Spectrum Disorder using joint MEG - DTI classification 
Madhura Ingalhalikar1, Drew Parker1, Timothy P.L. Roberts2, and Ragini Verma1
1Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Lurie Family Foundations MEG Imaging Center, Childerns Hospital of Philadelphia, Philadelphia, PA

This work presents a paradigm for generating a pathology based marker of language impairment (LI) in Autism Spectrum Disorder (ASD). This is achieved by combining MEG and DTI features in a pattern classifier. These classifiers, in addition to group separation have a potential to quantify the degree of LI by assigning an abnormality score to each subject. Furthermore, the ranking of features gives a physiological insight into the pathology. A 3-way classification between LI-ASD, non-LI-ASD and typically developing (TD) controls was achieved with an average accuracy of 71.69% providing better understanding of LI than just using individual modalities.

2333.   Fiber tracking of the Arcuate Fasciculus in Autism using High Angular Resolution Diffusion Imaging 
Harini Eavani1,2, Luke Bloy2,3, John Herrington1, Timothy L. Roberts4, Robert T Schultz1, and Ragini Verma2
1Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 2Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 3Department of Bioengineering, University of Pennsylvania, 4Lurie Family Foundations MEG Imaging Center

High Angular Resolution Diffusion Imaging(HARDI) is a new diffusion imaging protocol that can model complex white-matter better than Diffusion Tensor Imaging(DTI), which cannot delineate fiber-tracts across regions with fiber-crossings. In this study we establish the superiority of HARDI over DTI in identifying tracts by tracking the ArcuateFasciculus(AF) in a clinical population of children(8-18years) with autism. Results show that the AF is tracked significantly better in HARDI than DTI in all subjects and is closer to its anatomical definition. This establishes the feasibility of HARDI acquisition in clinical populations and can provide novel insight into the disease with subsequent tract-based analysis.

2334.   HARDI Fiber Tracking is Necessary to Delineate the Auditory Radiation 
Jeffrey I Berman1,2, and Timothy P. L. Roberts1,2
1Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States, 2Radiology, University of Pennsylvania, Philadelphia, PA, United States

It is necessary to develop robust methods of delineating the entire auditory radiation for quantitative studies in children with autism or language impairments. This work demonstrates the consistent ability of high angular resolution diffusion imaging (HARDI) fiber tracking to delineate the full length of the auditory radiation in a population of children. Diffusion MR was acquired from 6 children with autism spectrum disorder and 3 control children on a 3T Siemens scanner. The ability of HARDI and DTI fiber tracking to delineate the full auditory radiation were compared. HARDI fiber tracking successfully delineated the auditory radiation at a significantly higher rate than DTI fiber tracking.

2335.   Spatial analysis of diffusion tensor tractography depicts local white matter changes 
Johanna Mårtensson1,2, Markus Nilsson2, Christina Elfgren3, Maria Landqvist3, Freddy Ståhlberg2,4, Christer Nilsson3, Danielle van Westen1,4, and Jimmy Lätt1
1Center for Medical Imaging and Physiology, Lund University Hospital, Lund, Skane, Sweden, 2Department of Medical Radiation Physics, Lund University Hospital, Lund, Skane, Sweden, 3Geriatric Psychiatry, Department of Clinical Sciences, Lund University Hospital, Lund, Skane, Sweden, 4Department of Diagnostic Radiology, Lund University Hospital, Lund, Skane, Sweden

We present a method for spatial evaluation of MRI tractography data based on track co-registration using anatomical landmarks. The feasibility for clinical use was tested in a patient group suffering from semantic dementia. The analysis pinpointed specific areas of the track bundle where differences existed between the patient and healthy control group.

2336.   Traumatic Brain Injury: Abnormal fractional anisotropy in the corpus callosum and its association with injury severity. 
Cheuk Ying Tang1,2, Emily Lauren Eaves1, Kristen Dams-O'Connor3, Lap Ho4, David Carpenter1, Johnny Ng1, Wayne Gordon3, and Giulio M Pasinetti2,4
1Radiology, Mount Sinai School of Medicine, New York, New York, United States, 2Psychiatry, Mount Sinai School of Medicine, New York, New York, United States, 3Rehabilitation Medicine, Mount Sinai School of Medicine, New York, New York, United States, 4Neurology, Mount Sinai School of Medicine, New York, New York, United States

Atrophy of the corpus callosum (CC) observed after traumatic brain injury (TBI) was assessed using diffusion tensor imaging. Prior to scanning, subjects completed a series of questionnaires to assess their emotional and cognitive functioning. A single severity score was ascertained for each TBI subject. TBI subjects reported lower emotional and cognitive scores and had lower fractional anisotropy (FA) in the CC compared to controls. The severity score negatively correlated with CC FA in the TBI group. This study indicates atrophy of the CC following TBI is due to demyelination and FA may be useful as a biological marker for TBI.

2337.   A Diffusion Spectrum Imaging Study on Mirror Neuron System in Schizophrenia 
Chieh-En Jane Tseng1, Wei-An Wang1, Yu-Chun Arica Lo2, Yi-Huan Markus Wu3, Chih-Min Liu4, Hai-Gwo Hwu4, and Wen-Yih Isaac Tseng3,5
1Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, 3Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan, 4Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, 5Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

The mirror neuron system (MNS) has been hypothesized to be important in imitation and social cognition. Recent fMRI studies have reported MNS deficits in schizophrenia. The purpose of this study is to evaluate the white matter structure between the two areas in which mirror neurons have been identified, namely inferior frontal gyrus and inferior parietal lobule. As compared with the neurotypicals, patients showed no significant difference in generalized fractional anisotropy (GFA) bilaterally. In patients, however, positive correlations were found between the scores of social withdrawal and the GFA bilaterally.

2338.   Changes in Correlations of Regional Visual Cortical Thickness with Optic Radiation Tract in Anisometropic Amblyopia 
shun qi1, Hong Yin2, feng yun mu3, and Yi Huan3
1xijin hospital,the fourth military medical university, xi'an, shaanxi, China, People's Republic of, 2xijing hospital, China, People's Republic of, 3xijing hospital

Previous studies indicated that there were regional changes in the white matter and grey matter in amblyopia and that can be detected by the diffusion tensor imaging (DTI) and the high-resolution MRI image. However, the exact relationships between cortical thickness of visual cortex and integrity changes of optic radiation (ORs) fibers in anisometropic amblyopia are still unclear. The purpose of this study was to determine whether the changes of the visual cortex associate with integrity changes in the ORs fibers in amblyopia.

2339.   fMRI and diffusion tensor imaging biomarkers for assessing optic pathway structure and function in patients with pituitary tumours 
Andrew David Nichols1, Brad Moffat2, Helen Danesh-Meyer3, and Andrew H Kaye4
1Department of Surgery RMH/WH, The University of Melbourne, Parkville, Victoria, Australia, 2Radiology, University of Melbourne, Parkville, Victoria, Australia, 3Ophthalmology, University of Auckland, Auckland, New Zealand, 4Department of Surgery (RMH/WH), The University of Melbourne, Parkville, Victoria, Australia

Pituitary tumours represent a significant proportion of intracranial tumours. Growth of pituitary tumours superiorly may cause compression of the optic chiasm and lead to visual failure or visual field deficits. This is potentially avoidable or reversible with surgical intervention. We have performed fMRI and DTI tractography on 7 patients with pituitary tumours to investigate the effects of pituitary tumours on the visual pathway. We believe that there is potential for fMRI and DTI biomarkers to improve and individualise the management of patients with pituitary tumours and influence timing of surgical intervention.

2340.   Diffusion Abnormalities Detected by Tract-Based Spatial Statistics in Children with Sickle Cell Disease 
Richard Alan Jones1, Binjian Sun1, Robert Clark Brown2, and Laura Hayes1
1Radiology, CHOA, Atlanta, GA, United States, 2Hematology, CHOA, Atlanta, GA, United States

Children with sickle cell disease (SCD) whose brains are normal on conventional MRI often demonstrate neurocognitive impairments. This study uses diffusion tensor imaging to demonstrate differences in the white matter between controls, SCD subjects with radiologically normal brains and SCD subjects with mild gliosis. Extensive changes in the white matter were found for the mean diffusivity with these changes being more widespread in the gliosis group. The majority of the significant changes in the fractional anisotropy were confined to the corpus callosum of the gliosis group. DTI appears to be a sensitive biomarker for assessing the severity of SCD.

2341.   White Matter Alterations in Euthymic Bipolar I Disorder, a DTI Voxel-Based Analysis 
Louise Emsell1,2, Wim Van Hecke3,4, Camilla Langan1, Gareth Barker5, Alexander Leemans6, Stefan Sunaert3, Peter McCarthy1, Rachel Skinner1, Dara M Cannon1, and Colm McDonald1
1NUI Galway, Galway, Co. Galway, Ireland, 2Developmental & Functional Brain Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia, 3Dept of Radiology, University Hospital Leuven, Belgium, 4University of Antwerp, Belgium, 5Institute of Psychiatry, London, United Kingdom, 6Imaging Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

This study sought to identify trait related white matter microstructural abnormalities in 35 prospectively confirmed euthymic bipolar I disorder patients compared to 44 control subjects in a diffusion tensor imaging voxel-based analysis. The results reveal bilateral reductions in fractional anisotropy in the posterior cingulum, callosal splenium, corticospinal tract and cerebellum in patients, with no increases in FA. Illness duration was associated with FA increase in the posterior limb of the internal capsule, however there appeared to be no effect of lithium status on FA. Subtle WM alterations may be present in BD in remission and predispose to illness episodes.

2342.   Quality Assessment in a DTI Multicenter Study 
Amritha Nayak1, Lindsay Walker1, Carlo Pierpaoli1, and . the Brain Development Cooperative Group2
1NICHD, National Institutes of Health, Bethesda, MD, United States,

Multicenter DTI studies are becoming increasingly popular for their ability to improve the statistical power of a study by recruiting a large number of subjects. Data from multicenter studies can be heterogeneous in nature when no strict quality control requirements are enforced. We have designed quality assessment criteria to enable the identification of protocol errors and artifacts in multicenter DTI data, and described strategies to remediate the data to make it more compatible between sites.

2343.   Probabilistic tractography algorithms for tracking the optic radiation (OR): Are they ready for the Neurosurgeon? 
Bradford A Moffat1, Jeremy Lim1, Pramit Phal1, Christopher Kokkinos1, and Patricia M Desmond1
1Radiology, University of Melbourne, Parkville, VIC, Australia

The OR is a very important white matter structure that has proven to be problematic to track using DWI tractography algorithms. The aim of this research was to investigate whether diffusion weighted MRI (DWI) data acquired within a clinical neuroradiology MRI protocol could be used to accurately and robustly visualize the OR. The results of this study show constrained spherical deconvolution methods to have significant performance advantages over traditional tensor based tractography algorithms. Such comparative studies are necessary to validate tractography as clinical tool for neuronavigation and biomarker of axonal integrity.

2344.   MEG-guided diffusion kurtosis imaging in patients with refractory epilepsy 
Samuel Lapere1, Evelien Carrette2, Paul Boon2, Kristl Vonck2, Xavier De Tiège3, Els Fieremans4, Ali Tabesh4, Eric Achten1, and Karel Deblaere1
1Department of Radiology, Ghent University Hospital, Ghent, Belgium, 2Reference Centre for Refractory Epilepsy, Department of Neurology, Ghent University Hospital, Ghent, Belgium,3Laboratoire de Cartographie Fonctionnelle du Cerveau, ULB-Hôpital Erasme, Brussels, Belgium, 4Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY 10016, United States

In patients with refractory epilepsy, diffusion tensor imaging (DTI) can non-invasively provide valuable information on the microstructure and architecture of brain tissue in vivo and can be used to detect and evaluate microstructural alterations of white matter, even beyond the visually abnormal area. However, DTI has an important limitation because it incorrectly assumes that water diffusion in biological tissues occurs in an unrestricted manner and follows a Gaussian distribution, in which the diffusion weighted signal attenuatestion occurs monoexponentially with the strength and duration of the diffusion gradient (i.e. b-value). Diffusion kurtosis imaging (DKI) is an extension of the DTI technique which takes the deviation of restricted water diffusion in biological tissues from the Gaussian distribution (i.e. excess kurtosis characterizing the non-monoexponential signal decay) into account, thereby offering a more sensitive method of detecting subtle microstructural changes in neural tissue, both in the predominantly anisotropic white matter and the more isotropic grey matter . In this study, DKI was used in patients with refractory epilepsy with unknown seizure focus to examine both the region indicated by a preceding magnetoencephalography (MEG) exam (i.e. magnetic dipole cluster) and, if present, the grey matter abnormality visible on anatomical MRI scans. In patients with refractory epilepsy, preliminary results suggest that when using MEG to locate the potential seizure focus, diffusion kurtosis imaging is able to identify microstructural changes in both grey and white matter. Mean, radial and axial kurtosis values in the grey matter abnormality were significantly decreased with respect to the normal-appearing contralateral side.

2345.   Probabilistic Tractography in Patients with Recurrent Malignant Gliomas 
Patricia E. Litkowski1, Victor Liu1, Kyung Peck2, Zhigang Zhang3, Kathryn Beal4, and Robert J. Young1
1Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States, 2Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States,3Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States, 4Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States

Malignant gliomas are highly invasive tumors with poor clinical outcomes. Current treatment includes uniform radiation around the tumor region. Diffusion tensor imaging (DTI) is a promising modality that may more effectively inform radiation planning, particularly for local tumor growth. We used DTI to construct probabilistic maps based on seed ROI surrounding the tumors. The high-risk areas determined in our analysis showed a strong correlation with the locations of tumor progression, suggesting that DTI may be useful in planning targeted radiation therapy.

2346.   Abnormal White Matter Integrity in Adolescent Students with Internet Addiction Disorder Revealed by Tract-Based Spatial Statistics 
Fuchun Lin1, Yan Zhou2, Yasong Du3, Lindi Qin2, Zhimin Zhao3, Jianrong Xu2, and Hao Lei1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics & Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, People's Republic of, 2Department of Radiology, RenJi Hospital, Jiao Tong University Medical School, Shanghai, China, People's Republic of, 3Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Jiao Tong University, Shanghai, China, People's Republic of

Tract-based spatial statistics was used to investigate white matter (WM) integrity in adolescent students with Internet addiction disorder (IAD). Compared to healthy subjects, IAD adolescent students show has abnormalities in many white matter regions including the orbital frontal, superior temporal WM, together with several commissural, association, and projection fibers. Moreover, FAs in the left genu of corpus callosum and the left anterior corona radiation were negatively correlated with behavioral features. Our findings suggested that IAD has some common neurobiological mechanisms with substance addictions and diffusion tensor imaging might be valuable in providing data on neurological prognosis for IAD.

2347.   Altered Integrity and Asymmetry of Association White Matter Tracts in Epilepsy with Mesial Temporal Sclerosis: Preliminary Results Using Diffusion Spectrum Imaging 
Y-C. Shih1, H-H. Liou2, K-C. Chu3, P-Y. Chen4, W-M. Huang5, F-H. Lin1, and W-Y. I. Tseng4,6
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, 2Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan, 3Graduate Institute of Electrical Engineering, National Taiwan University, Taipei, Taiwan, 4Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, 5Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan, 6Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

In this study we investigated three association fibers including superior fronto-occipital fasciculus, cingulum bundles (CG) and uncinate fasciculus using diffusion spectrum imaging, and characterized the alteration in these association fibers in seven patients with left mesial temporal lobe epilepsy (mTLE) compared to controls. The patients showed increased structural connectivity in all association fibers except the inferior portion of the left CG. Furthermore, the CG changed its asymmetry from leftward to rightward. Our results suggest that the integrity of left CG ipsilateral to mTLE is affected directly. The increased structural connectivity in other tracts implies a mechanism of white matter plasticity.

2348.   Diffusion Abnormalities in Young Drug Naive ADHD Children 
Manzar Ashtari1, Carolyn Mcilree2, Melissa Naraine3, Laura Cyckowski4, Ruth Milanaik3, Li Kan3, Jeffrey Newcorn5, Josephine Elia1, and Andrew Adesman3
1Children's Hospital of Philadelphia, Philadelphia, PA, United States, 2University of Vermont Medical School, 3North Shore LIJ Health Systems, 4Children's Hospital of Philadelphia, 5Mount Sinai School of Medicine

This study is relevant to public health by further developing the science base regarding the white matter abnormalities underlying childhood ADHD as well as providing new insights into relationship between dopamine dysfunction and white matter development in ADHD children.

2349.   Validation of reduced Fractional Anisotropy measures in the Substantia Nigra of Parkinson's Patients using DAT Imaging 
Lorna Harper1,2, Edward Newman1,2, Donald Hadley1,2, and Donald Grosset1,2
1University of Glasgow, Glasgow, Scotland, United Kingdom, 2Institute of Neurological Sciences, Glasgow, Scotland, United Kingdom

This study aims to validate previous work demonstrating a reduction in fractional anisotropy (FA) measured in the substantia nigra (SN) of Parkinson’s Disease (PD) patients. DTI studies were acquired in twenty patients together with dopamine transporter (DAT) imaging. DAT imaging was used to confirm the clinical diagnosis of PD before correlation between the radioligand uptake in the striatum and FA measured in the SN was investigated. Two of the patients were found not to have PD; however they also demonstrated a reduction in FA. No correlation was found between FA measured in the SN and radioligand uptake in the striatum.

2350.   Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging 
Elin Haf Davies1, Kiran Seunarine2, Ashok Vellodi3, Tina Banks4, and Chris A Clark2
1Metabolics, Institute of Child Health, London, United Kingdom, 2Neuroimaging and Biophysics, Institute of Child Health, London, United Kingdom, 3Metabolic, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, 4Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom

Gaucher disease is a lysosomal storage disorder. Diffusion Tensor Imaging (DTI) examines brain white matter tracts - expressed as fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity. Tract-based spatial statistics was used to compare DTI parameters in Gaucher patients to age-sex matched controls. Decreased FA and increased MD was observed in Type III patients, primarily in the middle cerebellar peduncle, with increased axial and radial diffusivity. Despite small, diffuse changes in FA and MD throughout the Type I brain, no significant difference is observed in the cerebellar peduncles. This is the first brain DTI study in Gaucher patients.

2351.   Longitudinal Tract Atrophy in Normal Aging and Alzheimer's Disease Measured Using Probabilistic Tractography 
Hojjatollah Azadbakht1, David M. Morris1, Hamied A. Haroon1, Brandon Whitcher2, Julie Snowden3, and Geoff J Parker1
1Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, University of Manchester, Manchester, United Kingdom, 2Clinical Imaging Centre, GlaxoSmithKline, London, United Kingdom, 3Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, Manchester, United Kingdom

While current literature has mainly focused on measuring the atrophy of whole brain, global grey and/or white matter (WM), specific lobes or grey matter structures (e.g. the hippocampus), it is likely that atrophy caused by conditions such as Alzheimer’s also affects WM tracts via degenerative processes. If specific tract systems are more prone to atrophy than others, then tractography-guided atrophy measurements may be more sensitive biomarkers of degeneration than less targeted methods. For this purpose, in this work we apply a novel method for quantifying the progression atrophy in Normal-Aged and AD subjects undergoing serial diffusion MRI scans 1-year apart.

2352.   Robust detection of white matter injury in individual patients after mild traumatic brain injury 
Namhee Kim1, Miriam Hulkower1, Young Park1, Tova Gardin1, Jeremy Smith1, Craig Branch1, and Michael Lipton1,2
1Gruss Magnetic Resonance Research Center, Department of Radiology, Albert Einstein College of Medicine, Bronx, NY, United States, 2Departments of Psychiatry and Behavioral Sciences, The Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United States

Group-wise analyses of DTI show white matter abnormalities in mild traumatic brain injury (mTBI). Due to variation in mechanism of injury, an approach to identifying loci of brain injury in individual subjects is needed to fully understand mTBI pathology and allow clinical diagnostic use of DTI. We propose a refined Z-score analysis of single subject FA data, which accounts for the variance in inference for an individual subject due to potentially high dependence on the composition of the control group. Our results demonstrate the robustness of the technique and its utility in consistently identifying white matter pathology in mTBI.

2353.   Diffusion tensor imaging detects axonal degeneration and its extent is associated with disability in chronic spinal cord injury 
Torben Schneider1, Zoltan Nagy2, Claudia AM Wheeler-Kingshott1, Alan J Thomson3, and Patrick Freund2,3
1Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, 2Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom,3Department of Brain Repair & Rehabilitation, UCL Institute of Neurology, London, United Kingdom

We assessed the integrity of the axonal architecture in the spinal cord rostral to a traumatic cervical lesion and explored the relationship between diffusion tensor metrics and clinical disability. FA and AD were lower and MD and RD higher in the cervical cord rostral to the site of injury when compared to controls. In SCI subjects, FA in the cervical cord was positively associated with impaired motor and sensory function in the right lateral cortico-spinal tract. We conclude that spinal atrophy and clinical disability relate to spinal microanatomical sequel of traumatic injury in its chronic phase.

2354.   Parahippocampal and thalamic diffusion abnormalities correlate with disease duration in temporal lobe epilepsy with unknown cause 
Simon Sean Keller1, Tobias Ahrens1, Siawoosh Mohammadi2, Gabriel Möddel1, Harald Kugel3, Bernd Weber4, E Bernd Ringelstein1, and Michael Deppe1
1Department of Neurology, University of Münster, Münster, Germany, 2Wellcome Trust Centre for Neuroimaging, University College London, United Kingdom, 3Department of Radiology, University of Münster, Münster, Germany, 4Department of Epileptology, University of Bonn, Germany

In this diffusion tensor imaging study, we show that patients with temporal lobe epilepsy with unknown cause (TLEu) have significant diffusion abnormalities of temporal lobe structures ipsilateral and contralateral to the side of seizure onset relative to age and sex matched neurologically healthy controls. We further show that bilateral parahippocampal and thalamic abnormalities correlate with the duration of TLEu.

2355.   Cluster-Based Statistics Along White Matter Tracts 
Demian Wassermann1, Peter Savadjiev1, Yogesh Rathi1, Sylvain Bouix1, Marek Kubicki1, Ron Kikinis1, Martha Shenton1, and Carl-Fredrik Westin1
1Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts, United States

We present a method for cluster-based analysis along white matter tracts. The method shows increased sensitivity with respect to state-of-the-art methods while retaining mathematical soundness. We prove our method on a specific white matter bundle in a population of 18 schizophrenic subjects and 23 healthy controls.