Animal Model - Other

Monday 1 June 2015

Dara L Kraitchman^1,2, Larry Gainsburg³, Jan Fritz², Patrick R Gavin⁴, Nathan Pate⁵, Elizabeth Ihms⁵, Joseph Mankowski⁵, and Rebecca Krimins^1,2
1Center for Image-Guided Animal Therapy, Johns Hopkins University, Baltimore, MD, United States, ²Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ³Mid-Atlantic Veterinary Neurology and Neurosurgery, Catonsville, MD, United States, ⁴M.R. Vets, Sagle, ID, United States,⁵Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, United States

MRI of client-owned pets as a diagnostic tool in veterinary medicine is becoming more prevalent. As in human medicine, the vast majority of MRI studies are neurological or musculoskeletal. In this education e-poster, we will present several MRI studies where pathological correlation was obtained to confirm common interpretations of MRI studies. We will also present useful information for performing veterinary diagnostic MRI in an academic medical center.

Teodora-Adriana Perles-Barbacaru^1,2, Bruno Miguel de Brito Robalo^1,3, Emilie Pecchi^1,2, Georges Emile Raymond Grau⁴, Monique Bernard^1,2, and Angèle Viola^1,2
1Centre de Résonance Magnétique Biologique et Médicale, CRMBM UMR CNRS 7339, Marseille, France, ²Aix-Marseille Université, Marseille, France, ³University of Lisbon, Institute of Biophysics and Biomedical Engineering, Lisbon, Portugal, ⁴Department of Pathology, Sydney Medical School, The University of Sydney, Camperdown, Australia

Changes in brain tissue microstructure in murine cerebral malaria were investigated with DTI. Mice were imaged before disease and after infestation with Plasmodium Berghei ANKA. A segmented EPI technique was used for brain DTI acquisitions. S₀, FA, ADC, λ₁, λ₂ and λ₃ maps were generated. Early after infestation, FA was significantly deceased in specific white matter tracts, when the neurological signs were not yet detectable. Increases in ADC and radial diffusitivities occurred during the peak of the disease. Loss of tissue anisotropy is a new hallmark of the disease that may help improve our understanding of CM pathogenesis.

Joseph Guy^1,2, Pascal Sati¹, Steven Jacobson³, Afonso C Silva⁴, and Daniel S Reich^1
1Translational Neuroradiology Unit, Neuroimmunology Branch, National Institute of Neurologic Disorders and Stroke, Bethesda, MD, United States, ²Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ³Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurologic Disorders and Stroke, Bethesda, MD, United States, ⁴Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurologic Disorders and Stroke, Bethesda, MD, United States

MRI and histology are two very different but uniquely useful approaches to investigate diseases in cerebral tissues. However, due to the inherent differences between the methods (particularly image resolution), it is difficult to combine them together to investigate small-scale features/pathology. This can be overcome with the use of custom-fit, 3D-printed cradles/slicers that maintain alignment and orientation of brains between MRI and tissue cutting. We applied this method in marmoset brains and obtained a highly precise comparison between in vivo MRI, ex vivo MRI, and histology.

Novel Brain Methods

Monday 1 June 2015

Madhwesha Rao¹, Neil Stewart¹, Graham Norquay¹, Paul Griffiths¹, and Jim Wild^1
1University of Sheffield, Sheffield, South Yorkshire, United Kingdom

Hyperpolarized 129Xe when inhaled into the lungs, dissolves into the blood and is transferred to the brain by systemic circulation. The aim of this work was to demonstrate high-resolution spectroscopy and 2D gradient echo imaging of Hyperpolarized 129Xe dissolved in the human brain at 1.5 T for the first time. In this study, we demonstrate HP 129Xe as a safe, non-invasive contrast agent for imaging of xenon (blood) delivery to different compartments of the human brain in vivo.

Nils Noorman¹, Sebastian Hirsch², Jürgen Braun³, Peter R. Luijten¹, Ingolf Sack², and Jaco J.M. Zwanenburg^1
1Department of Radiology, University Medical Center, Utrecht, Utrecht, Netherlands, ²Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany,³Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany

The pulsating heart induces volumetric strain pulsations in the brain, which drive the interstitial transport of metabolites and waste products. This feasibility study mapped these volumetric strain rates for the first time with a time resolved 3-dimensional phase contrast (3D PCA) sequence (0.3 cm/s encoding velocity), over the entire brain and cardiac cycle (74 ms temporal resolution). The shapes of the strain rate curves obtained in four volunteers were similar to previous studies using different techniques. However, the magnitude was approximately 5 times larger, requiring further validation before using this technique as a tool for studying brain (patho)physiology.

Tie-Qiang Li¹, Rolf Hallin², and Jan-Erik Juto^3
1Department of Medical Physics, Karolinska University Hospital, Karolinska Huddinge, Stockholm, Sweden, ²Department of Neurophysiology, Karolinska University Hospital, Karolinska Huddinge, stockholm, Sweden, ³Department of CLINTEC, Karolinska Institute, Huddinge, stockholm, Sweden

Kinetic oscillatory stimulation (KOS) in the nasal cavity has been shown to be effective for treating acute migraine and inflammation. We aimed to better understand the neurological mechanisms underlying KOS treatment. We used a resting-state fMRI protocol that fits the treatment inside MRI scanners and a metric based on the number of significant functional connections to quantify BOLD response to KOS treatment. Our results demonstrate that migraine is associated with enhanced functional modulations within the control network of the autonomous nervous system and KOS treatment results in significantly different responses between normal controls and migraine patients.

Shinya Yamada¹, Yuichi Yamashita², Masao Yui², Cheng Ouyang³, Masao Nakahashi², and Mitsue Miyazaki^3
1Toshiba Rinkan Hospital, Sagamihara, Kanagawa, Japan, ²Toshiba Medical Systems Corp., Tochigi, Japan, ³Toshiba Medical Research Institute, Illinois, United States

The effect of respiration on CSF movement was investigated using a non-contrast time-spatial labeling inversion pulse (Time-SLIP) with balanced steady-state free precession (bSSFP) cine readout. CSF moved cephalic (16.4 ± 7.7 mm) during deep inhalation and caudal (11.6 ± 3.0 mm) during deep exhalation in the prepontine cisternal area. Small but rapid cephalic (3.0± 0.4 mm) and caudal (3.0 ± 0.5 mm) movement was observed in the same region during breath holding. Time-SLIP bSSFP cine presents for non-invasive visualization of CSF movement associated during deep expiration and expiration to a degree not previously reported.

Angelique Van Ombergen¹, Ben Jeurissen², Floris Vanhevel³, Dirk Loeckx⁴, Vincent Dousset⁵, Paul M. Parizel³, and Floris L. Wuyts^1
1Antwerp University Research centre for Equilibrium and Aerospace, University of Antwerp, Edegem, Antwerp, Belgium, ²iMinds/Visionlab, Department of Physics, University of Antwerp, Antwerp, Belgium, ³Department of Radiology, Antwerp University Hospital, Edegem, Antwerp, Belgium, ⁴icoMetrix, Leuven, Belgium,⁵Neuroradiology Department, CHU Pellegrin, Bordeaux, France

This study is a part of a larger study where we investigate for the first time ever the possible effects of gravity transitions on brain connectivity and morphology. We used voxel-based morphometry (VBM) to assess anatomical differences throughout the brain in 16 healthy and first-time parabolic flyers. MRI investigations were carried out before and immediately after the parabolic flight. Our results suggest that gravity shifts have an impact on brain morphology and possibly also connectivity, in regions that are know to play a pivotal role in the integration of neurosensory information (vestibular, visual and proprioceptive info).

Lisha Yuan¹, Jianhui Zhong¹, and Hongjian He^1
1Center for Brain Imaging Science and Technology, ZheJiang University, Hangzhou, Zhejiang, China

In addition to magnetic susceptibility, a potential source of motion artifact could be image-processing operations. As one of most typical image process, spatial resampling is demanded by head-motion correction of functional images. It deals with interpolation among neighboring voxels, and could be problematic when local signal is not homogeneous. The goal of this study was to evaluate the spatial resampling process during motion correction, and to verify that this artifact occurs at areas can be easily affected by the partial volume effect. In order to exclude the effect of motor-related neural activity, simulation experiments were designed and three types of data were created corresponding to common types of head motion.

Kazunobu Tsuji¹, Tatsuro Tsuchida¹, Yasuhiro Fujiwara^1,2, Masayuki Kanamoto¹, Tsuyoshi Matsuda³, R. Marc Lebel⁴, and Hirohiko Kimura^1
1Radiology, University of Fukui, Yoshida-gun, Fukui, Japan, ²Medical Imaging, Kumamoto University, Kumamoto, Japan, ³Global MR Applications and Workflow, GE Healthcare, Tokyo, Japan, ⁴Global MR Applications and Workflow, GE Healthcare, AB, Canada

Arterial spin labeling (ASL) signals reflect blood flow delivery to local brain tissue, but may be affected by arterial transit time (ATT). Low-resolution ATT pre-scan has been proposed as a means of reducing the ATT contribution1. Reproducibility studies have recently been reported from several groups using different ASL schemes, but no reports have described the reproducibility of ATT and ATT-corrected CBF. This study was to assess the reproducibility and reliability of ATT and ATT-corrected CBF maps compared with those of uncorrected CBF calculated using fixed transit time delay.

Steffi Dreha-Kulaczewski¹, Arun Jospeh^2,3, Klaus-Dietmar Merboldt², Hans Ludwig⁴, Jutta Gaertner¹, and Jens Frahm^2,3
1Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Goettingen, Germany, ²Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut fuer biophysikalische Chemie, Goettingen, Germany, ³partner site Goettingen, German Center for Cardiovascular Research, Germany,⁴Department of Neurosurgery, Division of Pediatric Neurosurgery, University Medical Center Goettingen, Germany

The mechanisms behind cerebrospinal fluid (CSF) flow in humans are still not fully known. We applied a novel real-time MRI technique at high spatial and temporal resolution in healthy subjects to study through-plane CSF flow in the third ventricle. Significant CSF flow was observed exclusively with inspiration (forced breathing protocol), whereas breath hold suppressed it. A small modulating flow component was ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow. This approach opens new opportunities to study the pathophysiology of various forms of hydrocephalus and to design appropriate therapeutic strategies.

Jean-Christophe Brisset¹, Riccardo Otazo¹, and Yulin Ge^1
1Department of Radiology, New York University School of Medicine, New York, NY, United States

Clinical imaging is always longing for increased image resolution to obtain superior details of biological structural changes at micro levels. SuperResolution is the process of reconstructing a High Resolution image from a Low Resolution image and has been predominantly used in digital photography and picture enhancement. Superresolution techniques have been proposed previously for MRI but with limited success due to scan time and SNR challenges. In this study, we propose to bring this idea to brain MRI for supersolved subvoxel microstructural diffraction. Coupled-sparsity superresolution may be very useful for identifying microstructures that are not well visualized with current MRI techniques.

Shunrou Fujiwara¹, Yoshichika Yoshioka², Tsuyoshi Matsuda³, Hideaki Nishimoto¹, Toshiyuki Murakami¹, Akira Ogawa¹, Kuniaki Ogasawara¹, Makoto Sasaki⁴, and Takaaki Beppu^1,5
1Department of Neurosurgery, Iwate Medical University, Morioka, Iwate, Japan, ²WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan, ³MR Applications and Workflow Asia Pacific, GE Healthcare Japan, Tokyo, Japan, ⁴Division of Ultrahigh Field MRI, Institu, Iwate Medical University, Yahaba, Iwate, Japan,⁵Hyperbaric Medicine, Iwate Medical University, Morioka, Iwate, Japan

We investigate the potential of cerebrospinal fluid (CSF) based DWI-thermometry measured in the subarachnoid space, where the CSF flow quietly changes comparing with the lateral ventricle, to estimate brain temperature (BT) in subacute carbon monoxide (CO) poisoned patients who show the strong imbalance between perfusion and metabolism in the brain. Our results suggested that the higher BT measured in the subarachnoid space by DWI than that measured in white matter by MRS might substantially reflect the brain metabolism in the subacute CO-poisoned patients because the CSF in the subarachnoid space directly lies on the cortex.

Fetal & Pediatric Neuroimaging: Clinical Studies

Monday 1 June 2015

Daphna Link^1,2, Michael Braginsky³, Leo Joskowicz³, Liat Ben Sira⁴, Gustavo Malinger⁵, Ariel Many⁶, and Dafna Ben Bashat^1,7
1Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ²Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ³School of Engineering and Computer Science, The Hebrew University of Jerusalem, Jerusalem, Israel, ⁴Division of Pediatric Radiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ⁵Obstetrics and Gynecology US Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ⁶Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ⁷Sackler Faculty of Medicine and Sagol school of neuroscience, Tel Aviv University, Tel Aviv, Israel

Accurate volumetric measurements of the fetal brain are clinically important to assess fetal development. In this study a novel semi-automatic segmentation method was used to extract and measure fetal brain volumes from high resolution MR images in fifteen typically developed and seven IUGR fetuses, and tested against manual segmentation validated by a senior neuro-radiologist. A good correlation was obtained between the algorithm and manual segmentation results (mean: 4.77% volume difference; 18.13% volume overlap difference) and with significantly reduced time taken (~99% less than manual segmentation). Furthermore, significant differences were detected between brain volumes of normal and IUGR fetuses.

Lillian Gabra Fam^1,2, Jeanie LY Cheong^1,3, Alexander Leemans⁴, Christopher L Adamson¹, Richard Beare¹, Marc L Seal^1,2, Peter J Anderson^1,2, Lex W Doyle^1,3, Alicia J Spittle^1,3, and Deanne K Thompson^1,5
1Murdoch Childrens Research Institute, Melbourne, Victoria, Australia, ²Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia, ³Royal Women’s Hospital, Melbourne, Victoria, Australia, ⁴Image Sciences Institute, University Medical Center Utrecht, Netherlands, ⁵Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia

Altered development of the white matter pathways linking the cerebellum and cerebrum may underlie some of the neurodevelopmental deficits in preterm infants. Few studies have reconstructed these tracts in the neonate brain. This study used probabilistic diffusion tractography to reconstruct the corticopontocerebellar and dentatothalamic tracts at term-equivalent age in 40 very preterm infants (<31 weeks’ gestation), 40 moderate and late preterm infants (32-36 weeks’ gestation) and 40 full-term controls (>37 weeks’ gestation). The corticopontocerebellar tracts were successfully reconstructed with clear delineation of their cortical projections. The dentatothalamic tracts were consistently reconstructed to the level of the superior cerebellar peduncle decussation.

J. Mitra¹, E. Conti^2,3, K-K. Shen¹, J. Fripp¹, O. Salvado¹, S. Calderoni², A. Guzzetta^2,3, and S. Rose^1
1Australian e-Health & Research Centre, CSIRO Digital Productivity Flagship, Herston, QLD, Australia, ²Dept. of Developmental Neuroscience, Stella Maris Scientific Institute, Pisa, Italy, ³University of Pisa, Pisa, Italy

Autism Spectrum Disorder (ASD) is a heterogeneous group of neuro-developmental diseases and is characterized by impairment in socio-communicative abilities, as well as restricted and stereotyped behaviours. There is a growing interest in identifying structural and functional neuro-anatomical correlates of the disorder that has the potential to predict early behavioural assessment impacting tailored rehabilitation intervention. In this study we analyse the diffusion MRI of ASD and developmental delay (DD) infants below 36 months of age and compare the differences in neural pathways using network based statistics. Further we analyse the asymmetry between the two cohorts from the obtained neural pathways.

Hye Jin Jeong¹, So-Yeon Shim², Dong Woo Son³, Mira Chung⁴, Sukyoung Park⁴, and Zang-Hee Cho^1
1Neuroscience Research Institute, Namdong-gu, Incheon, Korea, ²Ewha Womans University, Division of Neonatology, Seoul, Korea, ³Gachon University, Division of Neonatology, Incheon, Korea, ⁴Gachon University, Department of Early Childhood Education, Gyeonggi Province, Korea

Our aim was to compare serial diffusion tensor imaging (DTI) data from preterm infants on magnetic resonance imaging with those from term controls and to investigate the white matter (WM) region associated with neuromotor outcomes.

Chao-Ying Wang¹, Shih-Wei Chiang^2,3, Ping-Huei Tsai^4,5, Hua-Shan Liu^4,5, Hsiao-Wen Chung², Hung-Wen Kao³, Chun-Jung Juan³, and Cheng-Yu Chen^4,5
1Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, Taiwan, ²Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, Taiwan, ³Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan, Taiwan, ⁴Imaging Research Center, Taipei Medical University, Taipei, Taiwan, Taiwan, ⁵Department of Medical Imaging, Taipei Medical University, Taipei, Taiwan, Taiwan

To quantitatively investigate the perfusion characteristics of the adenohypophysis using DCE MR imaging in a group of ICCP children with normal pituitary morphology.

Zhiqiang Li¹, Houchun H Hu², Dinghui Wang¹, Jeffrey H Miller², John P Karis³, and James G Pipe^1
1Imaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²Radiology, Phoenix Children's Hospital, Phoenix, AZ, United States, ³Neuroradiology, Barrow Neurological Institute, Phoenix, AZ, United States

Cartesian SE or TSE sequence suffers from flow-related artifacts in post-contrast T1-weighted imaging. A spiral SE technique has been proposed to reduce the flow artifacts while providing faster scan speeds. In this preliminary study, the spiral SE sequence was evaluated and compared to Cartesian TSE mDixon in the pediatric group. Both independent radiologists rated spiral SE as superior to Cartesian TSE on flow artifact reduction and overall quality. Spiral SE also provides advantages such as fast scan speed and dark vascular signal. Therefore, spiral SE provides a viable alternative in post-contrast T1-weighted imaging.

Christopher G. Watson^1,2, Mathieu Dehaes³, Borjan A. Gagoski³, P. Ellen Grant^3,4, and Michael J. Rivkin^1,4
1Neurology, Boston Children's Hospital, Boston, MA, United States, ²Graduate Program for Neuroscience, Boston University, Boston, MA, United States, ³Newborn Medicine, Boston Children's Hospital, MA, United States, ⁴Radiology, Boston Children's Hospital, Boston, MA, United States

Arterial spin labeling (ASL) has not been extensively used in the acute stage of neonatal stroke. We aimed to establish whether acquiring ASL in neonatal stroke is feasible, and determine if distinct perfusion patterns are evident in arterial and venous stroke types. Of 23 neonates with acceptable ASL data, we found that hyperperfusion was more common in arterial stroke, and hypoperfusion was only present in venous stroke. Additionally, clinical seizures occurred only in arterial stroke. We conclude that ASL acquisition is feasible in neonates with acute stroke. Hyperperfusion may be due to reperfusion or to increased neuronal activity in seizures.

Tanya Poppe¹, Myra Leung¹, Anna Tottman², Jane Alsweiler³, Frank Bloomfield², Jane Harding², and Ben Thompson^1,4
1Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand, ²Liggins Institute, University of Auckland, Auckland, New Zealand,³Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand, ⁴Department of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada

This study revealed that a higher order visual pathway, thought to be sensitive to abnormal neurodevelopment, could be assessed using fMRI in seven-year-old children. Furthermore, the fMRI results were correlated with cortical thickness and performance of a visual task outside of the scanner environment. These findings are consistent with electrophysiology (in non-human primates), electroencephalography (EEG), and magnetoencephalography (MEG) studies in adults. fMRI of visual brain areas may provide a sensitive biomarker for abnormal neurodevelopment in children.

Normal Developing Brain

Monday 1 June 2015

Justin M Remer¹, Douglas C Dean III^1,2, Sara D'Arpino¹, Elise Croteau-Chonka¹, Holly Dirks¹, and Sean C.L. Deoni^1,3
1Advanced Baby Imaging Lab, School of Engineering, Brown University, Providence, RI, United States, ²Waisman Lab for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States, ³Department of Pediatric Radiology, Children's Hospital Colorado, Aurora, CO, United States

Cortical development is a rapid and dynamic process that has been shown been shown to be a predictive measure of cognitive development in adolescents. Longitudinal developmental trajectories of cortical thickness from 163 healthy, typically developing infants and children were characterized using non-linear mixed effects modeling and shown to exhibit both linear and non-linear behavior. In addition, differential cortical development based on early learning composite, a surrogate measure of IQ, was observed in three specific brain regions. Our results provide insight into the complexities behind cortical maturation and provide an important foundation for understanding typical cortical development.

Jessica Lebenberg¹, Cyril Poupon², Bertrand Thirion³, François Leroy¹, Jean-François Mangin⁴, Ghislaine Dehaene-Lambertz¹, and Jessica Dubois^1
1Cognitive Neuroimaging Unit U992, INSERM-CEA, Gif-Sur-Yvette, Essonne, France, ²UNIRS, CEA, Gif-Sur-Yvette, Essonne, France, ³Parietal, INRIA, Gif-Sur-Yvette, Essonne, France, ⁴UNATI, CEA, Gif-Sur-Yvette, Essonne, France

The human brain rapidly matures during the first post-natal weeks. Microstructural and physiological changes considerably affect MRI parameters offering the possibility to non-invasively follow brain maturation in healthy infants. Here, we propose to combine complementary quantitative parameters related to DTI and relaxation times to characterize maturation without spatial a priori across the brain, including both the cortex and white matter. We reproduced results obtained in post-mortem studies: the first mature regions included primary regions; the maturation progressed rapidly but differently depending on brain regions. In future analyses, we will propose new brain partitions based on such maturation patterns.

Douglas Dean ^1,2, Elise Croteau-Chonka², Holly Dirks², Andrew L. Alexander¹, and Sean Deoni^2,3
1Waisman Center, University of Wisconsin-Madison, Madison, WI, United States, ²Engineering, Brown University, Providence, Rhode Island, United States, ³Children’s Hospital Colorado, Dever, Colorado, United States

Myelination is a critical process of white matter development. While several neuroimaging techniques have been used to study white matter development, no prior studies have directly examine the microstructural properties of myelin. In this work, we present an alternative approach, combining multicomponent relaxometry and NODDI data, to measure the myelin g-ratio and for the first time present developmental trajectories of the myelin g-ratio during neurodevelopment.

Andrea S. Miele^1,2, Holly Dirks², Dannielle John Whiley², Terry Harrison-Goldman^1,3, Viren D'Sa³, and Sean Deoni^2,4
1Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, United States, ²Advanced Baby Imaging Laboratory, Brown University, Providence, Rhode Island, United States, ³Pediatrics, Neurodevelopmental Center, MHRI, Pawtucket, Rhode Island, United States, ⁴Pediatric Radiology, Children's Hospital Colorado, Colorado, United States

Dyslexia is a language-based learning disability characterized by deficits in phonological processing, a set of skills considered essential for reading acquisition. To our knowledge, no study has yet investigated the relationship between myelin maturation in toddlers and later phonological awareness skills. Participants were grouped by level of performance on a well-researched and validated measure of phonological awareness (PA), and mixed effects modeling utilized to plot MWF growth curves. Longitudinal trajectories revealed increasing MWF by age. High PA performers had greater myelin content (p<.05) in the temporal lobe but less myelin content (p<.05) in the frontal lobe compared to low performers.

Xi Tan¹, Jannine Cody², and Jack L Lancaster^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

18q- is a chromosomal disease. People with 18q- miss part of the long arm (q arm) of one copy of chromosome 18. Since people with 18q- are typically mental retarded and developmental delayed, this study investigated whole brain volume, grey matter volume and white matter volume development on the age rang 0-25 years old, and the linear effect of deletion size on the these volumes. It proved that deletion size have a negatively linear effect on these volumes, and 18q- volumes grow quicker to reach equilibrium volumes, but their equilibrium volumes are smaller than normally developed control subjects’.

Yiran Chen¹, Robert Bok¹, Subramanian Sukumar¹, Hosung Kim¹, Xin Mu¹, Ann Sheldon¹, A James Barkovich¹, Donna M Ferriero¹, and Duan Xu^1
1University of California San Francisco, San Francisco, CA, United States

In this study, we applied dynamic nuclear polarization (DNP) technique to investigate C1 labeled 13C pyruvate to lactate conversion and T2-weighted MRI for brain volume analysis across maturation in mice in vivo. Normal mice were scanned starting on postnatal day 18 and repeated every 10 days. Lactate level was significantly higher at younger ages, and decreased with increase in age. No significant global brain volume growth was observed after P18.

Ivan Tkac¹, Kathleen Czerniak², Lanka Dasanayaka², Biplab Dasgupta³, and Raghavendra Rao^2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States, ³Division of Hematology/Oncology, Cincinnati Children's Hospital, Cincinnati, OH, United States

Mouse models are often used in studies of the brain development. Rapid postnatal changes in neural cell populations, their size and their maturation result in major changes in metabolite levels. Therefore, the knowledge of regionally specific neurochemical changes in normal mouse brain development is required. In this study we use ¹H MRS at 9.4T to quantify neurochemical profiles of the midbrain and hippocampus in a common C57BL/6 mouse strain at postnatal days (P)10 and P28. These neurochemical profiles and their changes are distinctively different. Relatively high levels of urea were detected in the brain at P10.

Xiao-Qi Ding¹, Helen Maghsudi¹, Andrew A. Maudsley², Mohammad Sabati², Sulaiman Sheriff², Martin Schütze¹, Paul Bronzlik¹, and Heinrich Lanfermann^1
1Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Lower Saxony, Germany, ²Department of Radiology, University of Miami School of Medicine, Miami, FL, United States

Metabolite concentrations in multiple brain structures of 60 healthy adults (21 - 70 years) were measured by using a short TE (17.6 ms) whole brain MR spectroscopic imaging (wbMRSI). The distributions as well as the age-related changes of brain metabolites NAA, tCho, tCr, mI, and Glx were regional and metabolite dependent. The most age-related changes were observed in metabolite NAA with age-related decreases in seven of thirteen selected brain structures and the cerebrum revealed more local metabolic changes than that in cerebellum.

Bonnie Alexander¹, Andrea Murray¹, Jian Chen^1,2, Wai Yen Loh^1,3, Claire Kelly¹, Richard Beare¹, Lillian Gabra Fam^1,4, Peter Anderson^1,4, Lex Doyle^1,5, Alicia Spittle^1,5, Jeanie Cheong^1,5, Marc Seal^1,4, and Deanne Thompson^1,3
1Murdoch Childrens Research Institute, Melbourne, Victoria, Australia, ²Dept of Medicine, Monash University, Melbourne, Australia, ³Florey Institute of Neuroscience and Mental Health, Melbourne, Australia, ⁴Dept of Paediatrics, The University of Melbourne, Melbourne, Australia, ⁵Royal Women's Hospital, Melbourne, Australia

This project addresses the need for a high quality neonatal brain atlas attuned to accommodate tissue types and morphological subtleties characteristic of this developmental stage. T2 MRI scans of 3 healthy term-born neonates were used. Cortical gray matter was segmented using an in-house pipeline incorporating the unified segmentation process implemented in SPM8. 33 cortical areas per hemisphere were manually traced corresponding to those in the Desikan-Killiany adult brain atlas. A structural template was generated using symmetric diffeomorphic transformation, and structure probability maps were constructed. The atlas produced will be incorporated into a freely accessible infant segmentation and parcellation toolbox.

Thomas Alderliesten^1,2, Esben Thade Petersen³, Manon JNL Benders^1,2, Petra MA Lemmers², Alessandro Allievi⁴, Julia Wurie¹, Serena J Counsell¹, Etienne Burdet⁴, A. David Edwards^1,4, Jo V Hajnal^1,5, and Tomoki Arichi^1,4
1Centre for the Developing Brain, King's College London, London, London, United Kingdom, ²Department of Neonatology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ³Department of Radiology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ⁴Department of Bioengineering, Imperial College London, London, United Kingdom, ⁵Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom

Functional MRI (fMRI) is being increasingly used in infants. However, the underlying blood oxygen level dependent (BOLD) contrast is qualitative in nature, and its biophysical origins in this population are poorly understood. By measuring cerebral blood flow, Arterial Spin Labeling (ASL) can add a quantitative dimension to fMRI. We therefore aimed to simultaneously measure functional ASL and BOLD responses following somatosensory stimulation (passive wrist movement) in infants during their first year by using a dual echo pCASL sequence. Eight infants were studied; ASL responses largely overlaid BOLD responses, but were less diffuse and more localized to the cortex.

Jonathan O'Muircheartaigh^1,2, Douglas C Dean³, Lindsay Walker⁴, Nicole Waskiewicz⁴, Holly Dirks⁴, and Sean Deoni^4,5
1Department of Neuroimaging, King's College London, London, United Kingdom, ²Centre for the Developing Brain, King's College London, London, London, United Kingdom,³Waisman Center, University of Wisconsin-Madison, Wisconsin, United States, ⁴School of Engineering, Brown University, Rhode Island, United States, ⁵Department of Pediatric Radiology, Children's Hospital Colorado, Denver, Colorado, United States

We report on cross-sectional study interrogating coupling between functional networks using resting-state fMRI in a technically challenging group, infants and young children aged 3 months to 5 years. We investigate the relationship between coupling between these functional networks and maturity. In addition we also interrogate the relationship between cognitive ability and connectivity. We demonstrate extensive positive and negative relationships in coupling between resting state functional networks, the relationship with cognitive ability is subtle and restricted. These results add to the growing literature on functional network interactions during development.

Lara Lordier¹, Frédéric Grouiller², Dimitri Van de Ville^2,3, Ana Sancho Rossignol⁴, Maria Isabel Cordero⁴, François Lazeyras², François Ansermet⁴, and Petra S. Hüppi^1
1Division of Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Geneva, Switzerland, ²Department of Radiology and Medical Informatics, Geneva University Hospital, Geneva, Switzerland, ³Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁴Division of Child and Adolescent Psychiatry, Department of Pediatrics, University of Geneva, Geneva, Switzerland

Previous studies in adults reported that spontaneous brain activity can be modulated by learning, training, but also by behavioral states, which is supporting the idea that low-frequency BOLD signal fluctuations are modulated by recent experience. We mapped resting state networks (RSNs) in nine newborns and investigate if these low-frequency BOLD signal fluctuations were modified after a heel prick. We observed RSNs similar to those previously found in adults and infants. Furthermore, we showed an increased connectivity between basal ganglia and orbitofrontal components reflecting the integration and modulation of the pain experience.

Xiawei Ou^1,2, R.T. Pivik^1,3, Aline Andres^1,3, Mario Cleves^1,3, and Thomas Badger^1,3
1Arkansas Children's Nutrition Center, Little Rock, AR, United States, ²Radiology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States,³University of Arkansas for Medical Sciences, AR, United States

The aim of this study was to evaluate brain function in healthy 8-year-old children who were fed predominantly breast milk or cow’s milk formula during the first year of life. Our hypothesis was that infant diet has significant effects on brain functioning in school aged children. To test this hypothesis, we performed a visual perception/language fMRI to compare brain activation in these two diet groups. Our results showed that breastfed and milk formula-fed children utilize their brain differently when processing the visual perception and language tasks.

Autism & Neuro Development

Monday 1 June 2015

Nathalie Doorenweerd^1,2, Eve M Dumas², Eidrees Ghariq^1,3, Sophie Schmid^1,3, Chiara S.M. Straathof², Pietro Spitali⁴, Ieke Ginjaar⁵, Beatrijs H Wokke², Debby G.M. Schrans⁶, Janneke C van den Bergen², Erik W van Zwet⁷, Andrew G Webb¹, Mark A van Buchem¹, Mathias J.P. van Osch^1,3, Jan J.G.M. Verschuuren², Jos G.M. Hendriksen^6,8, Erik H Niks², and Hermien E Kan^1,3
1Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Zuid Holland, Netherlands, ²Department of Neurology, Leiden University Medical Center, Leiden, Zuid Holland, Netherlands, ³Leiden Institute for Brain and Cognition, Leiden, Zuid Holland, Netherlands, ⁴Department of Human Genetics, Leiden University Medical Center, Leiden, Zuid Holland, Netherlands, ⁵Department of Clinical Genetics, Leiden University Medical Center, Leiden, Zuid Holland, Netherlands, ⁶Department of Neurological Learning Disabilities, Kempenhaeghe Epilepsy Center, Heeze, Noord-Brabant, Netherlands, ⁷Department of Medical Statistics, Leiden University Medical Center, Leiden, Zuid Holland, Netherlands, ⁸Department of Neurology, Maastricht University Medical Center, Limburg, Netherlands

In addition to muscle weakness, Duchenne muscular dystrophy (DMD) is characterized by specific learning and behavioral disabilities. DMD is caused by mutations in the DMD gene leading to absence of one or more isoforms of the dystrophin protein, which is expressed in muscle, brain, vascular endothelial and smooth muscle cells. We used pCASL to show a reduction in cerebral blood flow in DMD patients compared to healthy controls. These changes were most profound in patients missing both full length dystrophin and Dp140, which suggests that full length and Dp140 play supplementary roles in the vascular involvement in DMD brain pathophysiology.

Yi-Shin Chang¹, Julia P Owen¹, Tony Thieu¹, Nicholas Pojman¹, Polina Bukshpun¹, Mari Wakahiro¹, Elysa Marco¹, Jeffrey Berman², John E Spiro³, Wendy Chung⁴, Randy Buckner⁵, Timothy Roberts², Srikantan Nagarajan¹, Elliott Sherr¹, and Pratik Mukherjee^1
1University of California in San Francisco, San Francisco, California, United States, ²Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, ³Simons Foundation, New York, New York, United States, ⁴Columbia University, New York, New York, United States, ⁵Harvard University, Boston, Massachusetts, United States

Copy number variants (CNVs) at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, and bipolar disorder. In this study, we demonstrate widespread and opposing white matter alterations in pediatric and adult human carriers of the 16p11.2 deletion versus the reciprocal duplication. We further show associations of cognitive and behavioral impairment with deviation in either direction from normative microstructural white matter values. These results support the view that specific genetic variations may be more strongly associated with changes in brain structure, including macrostructure and microstructure, than shared neuropsychiatric diagnoses.

Yu-Chun Lo¹, Yu-Jen Chen¹, Yung-Chin Hsu¹, Susan Shur-Fen Gau^2,3, and Wen-Yih Isaac Tseng^1,4
1Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ²National Taiwan University College of Medicine, Department of Psychiatry, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, ⁴Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

Impaired performance in social communication has been consistently found in autism spectrum disorder (ASD). We used diffusion spectrum imaging to measure white matter property of the social communication network, and investigated its relationships with social communication and social awareness for 56 ASD and 44 neurotypicals. ASD showed reduced white matter integrity of the social communication network as compared to neurotypicals. Unique correlations were found between white matter integrity and the social communication ability in ASD. Our results indicate altered functional and structural roles of cores of the social communication network in ASD.

Qi Liu¹, Lizhou Chen¹, Ying Chen², Xinyu Hu¹, Ming Zhou¹, Fei Li¹, Lanting Guo², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²Deptmeny of Psychiatry, West China Hospital of Sichuan University, P.R.China, Chengdu, Sichuan, China

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood. The present study aimed to explore the brain structural changes between medicated-naïve male ADHD and healthy controls. Finally, we found that subcortical volumes of bilateral putamen and amygdala were smaller in ADHD group, and those changes were significantly correlated with clinical measurements for behavioral problems and some specific executive domains. This suggested that putamen and amygdala may play key roles in ADHD.

Douglas Dean ¹, Brittany Travers¹, Erin Bigler², Molly Prigge³, Alyson Froehlich³, Nicholas Lange⁴, Janet Lainhart¹, and Andrew Alexander^1
1Waisman Center, University of Wisconsin-Madison, Madison, WI, United States, ²Brigham Young University, Provo, UT, United States, ³University of Utah, Salt Lake City, UT, United States, ⁴Harvard School of Medicine and McLean Hospital, Belmont, MA, United States

Brain imaging findings in children with autism spectrum disorder (ASD) suggest the disorder is associated with altered brain development and disrupted structural and functional brain “connectivity," which implies atypical white matter microstructure in at least some parts of the brain in ASD. However, it is unclear how homogeneous the structural organization of the white matter microstructure is within the brains of individuals with ASD at different ages. In this work, we examine correlations among the microstructure of different white matter tracts in childhood and adulthood in ASD compared to typical development.

Letizia Casiraghi^1,2, Fulvia Palesi^2,3, Gloria Castellazzi^2,4, Andrea De Rinaldis^2,4, Carol Di Perri⁵, Claudia AM Wheeler-Kingshott⁶, and Egidio D'Angelo^1,2
1Department of Brain and Behavioral Sciences, University of Pavia, Pavia, PV, Italy, ²Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, PV, Italy,³Department of Physics, University of Pavia, Pavia, PV, Italy, ⁴Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, PV, Italy,⁵Department of Brain and Behavioural Sciences, University of Pavia, Pavia, PV, Italy, ⁶NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom

Autism Spectrum Disorder (ASD) children present atypical brain functioning. We assessed the functional connectivity of altered grey matter (GM) regions. Areas of increased volume in ASD presented FC increments and reductions whereas reduced density areas presented FC reductions only. Correlations between FC and clinical scores indicate that the more extreme the FC the more severe the impairment. Our results support the idea that temporal and subcortical areas are responsible for the sensory integration and emotional deficits while occipital areas and insula are strongly involved in deficit linked to the integration of visual stimuli and self-awareness information.

Lizhou Chen¹, Ning He², Qi Liu¹, Xinyu Hu¹, Lanting Guo², Xiaoqi Huang¹, and Qiyong Gong^1
1Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, China

To explore the emotional network in children with Attention-deficit/hyperactivity disorder. We demonstrated abnormal functional connectivity which involved the amygdala, basal ganglia and cerebellum, providing new evidence to the pathophysiology of emotion dysregulation in this disorder.

Houshang Amiri^1,2, Amanda Jager², Sjaak J. A. van Asten¹, Arend Heerschap¹, and Jeffrey Glennon^2
1Department of Radiology, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands, ²Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands

Aggressive behaviour is a key symptom of conduct disorder (CD). Therefore, animal models of aggression could provide more knowledge about the neural substrates underlying CD and could provide new insights in possible treatments to treat or prevent this disorder. We first extensively phenotyped the BALB/cJ mice (as an aggressive model) in terms of aggression, anxiety, impulsivity, compulsivity and attention. Then, a multiparametric MR experiment including DTI, ASL, and MRS was performed. Our findings suggest that pathological aggression observed in the BALB/cJ mice is likely related to structural and neurochemical changes leading to inattention and anxiety.

Hsiang-Yun Sherry Chien¹, Susan Shur-Fen Gau², Yu-Jen Chen¹, Yu-Chun Lo¹, Hsiang-Yuan Lin², Yung-Chin Hsu¹, and Wen-Yih Isaac Tseng^1,3
1Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ²Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ³Molecular Imaging Center, National Taiwan University, Taipei, Taiwan, Taiwan

In the present study, we investigated the functional connectivity (FC) and structural connectivity (SC) within default mode network (DMN) simultaneously in normal adolescents and adolescents with autism spectrum disorder (ASD). We found that all the indices tended to be lower in adolescents with ASD compared to TD, especially in the SC of the right cingulum. Furthermore, the FC-SC correlation patterns showed opposite directions on both sides and were significantly different on the right side between the two groups. This might imply the abnormal DMN development in individuals with ASD during their adolescence.

Mohammed Syed¹, Zhi Yang², and Gopikrishna Deshpande^3,4
1Department of Computer Science and Software Engineering, Auburn University, Auburn, AL, United States, ²Key Laboratory of Behavioral Sciences, Institute of Psychology, Chinese Academy of Sciences, Beijing, China, ³Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States,⁴Department of Psychology, Auburn University, Auburn, AL, United States

Autism is a heterogeneous spectrum disorder, hence fMRI connectivity metrics derived from the autism group may not be highly reproducible within that group, leading to poor generalizability which in turn leads to lower classification accuracies. We hypothesize that functional brain networks that are most reproducible within autism and healthy control groups separately, but not when the two groups are merged, may possess the ability to distinguish effectively between the groups. We characterize reproducibility of networks using ‘generalized Ranking and Averaging Independent Component Analysis by Reproducibility’ (gRAICAR) algorithm and provide evidence in support of the above hypothesis.

Loredana Sorina Truica¹, Sarah Raza¹, J. Keiko McCreary¹, Ian Q. Whishaw¹, and Robbin Gibb^1
1Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada

Human neuroimaging studies have shown abnormal regulation of brain growth in autism spectrum disorders (ASD), suggesting that processes governing apoptosis and synaptic pruning are highly implicated. This study investigates brain tissue changes in the valproic acid (VPA) animal model of ASD and placental transfer of the drug. Brain and placental in vivo T2-relaxometry measurements were conducted. Results showed differences between VPA and control groups in the prefrontal cortex, suggesting that prenatal exposure to VPA altered the expected neuronal density. Placental transfer was evident in the T2 maps. This outcome supports the evidence that VPA impacts fetal development pre and post-natally.

Jacob Ellegood¹, Jan Scholz¹, Mark Henkelman^1,2, and Jason P Lerch^1,2
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, ²Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Current research has shown volumetric differences in 26 different mouse models related to autism. The purpose of this work is to use diffusion tensor imaging (DTI) to further examine the structural connectivity differences in 13 of those mouse models to further investigate the white matter differences. Surprisingly only 3 of the 13 models had differences in fractional anisotropy and mean diffusivity.

Manoj Kumar¹, Jeff T Duda¹, Sea-Young Yoon², Jessica Bagel³, Patricia O’Donnell³, Charles Vite³, Stephen Pickup¹, James C Gee¹, John H Wolfe², and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Research Institute of the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, ³School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States, Pennsylvania, United States

Alpha-mannosidosis is an autosomal recessively inherited lysosomal storage disorder, caused by deficiency of the enzyme alpha mannosidase. We performed ex-vivo diffusion tensor imaging (DTI) and in vivo DTI on AMD affected and wild type cat brains to assess brain abnormalities. A multi-atlas approach was used to generate a brain template and process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA) and mean diffusivity (MD) values from gray and white matters from whole brain. Region of interest based DTI data analysis was also from ex vivo and in vivo DTI from six gray and five white matter regions. Significantly reduced FA was observed from both the ex vivo and in vivo DTI data from all the white matter in AMD affected cats may be suggestive of gliosis or demyelination. Some of the analyzed gray matter also demonstrates significantly reduced FA in AMD affected cats.

Robert X Smith¹, Devora Beck-Pancer², Rosemary McCarron², Kay Jann¹, Leanna Hernandez², Mirella Dapretto², and Danny JJ Wang^1
1Neurology, UCLA, Los Angeles, CA, United States, ²Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United States

We investigate the relationship between local neural activity and network organization in a cohort of children with autism spectrum disorders (ASD) and typically developing children. We employ wavelet-based regularity analysis, a recently developed measure of resting-state functional MRI signal dynamics, in conjunction with seed-based functional connectivity. We find widespread regions across the prefrontal cortex in children with ASD that exhibit 1) increased signal irregularity, 2) bilateral decreases in long-range correlations to posterior areas, and 3) disorganized increases to local frontal regions. These results provide strong evidence implicating atypical neural activity in the disruption of long-range association pathways.

Normal Brain fMRI

Monday 1 June 2015

Adnan A.S. Alahmadi^1,2, Matteo Pardini^1,3, Rebecca S Samson¹, Karl J Friston⁴, Ahmed T Toosy^1,5, Egidio D’Angelo^6,7, and Claudia A.M. Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Department of Diagnostic Radiology, Faculty of Applied Medical Science, KAU, Jeddah, Saudi Arabia, ³Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy, ⁴Wellcom Centre for Imaging Neuroscience, UCL, Institute of Neurology, London, United Kingdom, ⁵NMR Research Unit, Department of Brain Repair and Rehabilitation, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom, ⁶C. Mondino National, Neurological Institute, Pavia, Italy, ⁷Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

We explored non-linear BOLD responses in the cerebellum using a grip task, with five grip forces. Linear responses were observed in the anterior lobules and non-linear responses were localized in the posterior lobules. Previous studies have shown that the cerebellum is involved in different non-motor functions and interestingly our findings confirm that the cerebellum behavior in response to a complex paradigm reflects the presence of an organized structure, similarly to what has been suggested by cortical fMRI studies. In particular, higher order effects are localized in the posterior of the cerebellum known to be involved in executive and sensory functions.

Jevin W. Zhang^1,2, Patrick P. Gao^1,2, Shu-Juan Fan^1,2, Dan H. Sanes³, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, ³Center for Neural Science, New York University, New York, NY, United States

The BOLD response in the inferior colliculus (IC) was stronger to the forward than to the inverted vocalizations despite their identical frequency spectrum, clearly demonstrating response selectivity. The selectivity was prominent in the external cortex of IC, but was not observed in the lateral lemniscus (LL). The response selectivity was nearly abolished following atropine injection. The results suggest that the auditory midbrain is the first place in the ascending auditory pathway to display response selectivity to vocalizations, and highlights the ability of fMRI in investigating the processing of behaviorally relevant sounds.

Yanlu Wang¹ and Tie-Qiang Li^1,2
1Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Stockholms Län, Sweden, ²Medical Physics, Karolinska University Hospital, Huddinge, Stockholms Län, Sweden

We have previously extracted functional connectivity networks from resting-state fMRI data using hierarchical clustering at voxel-level while retaining full-brain coverage. Hierarchical clustering algorithm is not only a data-driven analysis method, but also naturally stratifies data in a hierarchical structure. Using this inherent property of the algorithm, we investigated the intra-network hierarchical organization of the visual network and showed that the intra-network connectivity conforms to the two-stream hypothesis of visual processing. This suggests that functional sub-division of resting-state functional connectivity networks through hierarchical clustering reflects the intra-network organization of resting-state functional connectivity networks.

Andrea Duggento¹, Marta Bianciardi², Lawrence L. Wald², Luca Passamonti³, Riccardo Barbieri^4,5, Maria Guerrisi¹, and Nicola Toschi^1,2
1Medical Physics Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy, ²Department of Radiology, A.A. Martinos Center for Biomedical Imaging, MGH and Harvard Medical School, Boston, MA, United States, ³Institute of Bioimaging and Molecular Physiology, National Research Council, Catanzaro, Italy, ⁴Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA, United States, ⁵Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, United States

We use 7T fMRI with simultaneous physiological signals acquisitions to investigate the causal interactions between resting state brain activity and autonomic nervous system (ANS) outflow as quantified through a probabilistic heartbeat model. We demonstrate the existence of significant causal links between cortical/subcortical brain regions and ANS outflow for (para)sympathetic modulation as well as sympathovagal balance, with a prominent involvement of cerebellar regions and Sensory Motor, Default Mode, Left executive and Right executive networks. 7T functional imaging coupled with Granger causality estimates is able to quantify directed brain-heart interactions reflecting directed central modulation of ANS outflow.

Silvia Francesca Storti¹, Ilaria Boscolo Galazzo², Francesca Pizzini², Stefania Montemezzi², Paolo Manganotti³, and Gloria Menegaz^1
1Department of Computer Science, University of Verona, Verona, Italy, ²Department of Neuroradiology, AOUI of Verona, Verona, Italy, ³Department of Neurological and Movement Sciences, University of Verona, Verona, Italy

The recent dual-echo arterial spin labeling (DE-ASL) technique has been proposed for the simultaneous acquisition of cerebral blood flow and blood oxygenation level dependent (BOLD) responses to brain activation. In order to compare the performance of DE-ASL and conventional BOLD-fMRI sequences for identifying regions involved in active and imagery movement, single-subject, group and statistical analysis were computed on a group of volunteers. DE-ASL has shown to be suitable for mapping brain functions as well as the fMRI-BOLD both during the movement task and during the imagination of the movement.

Shu-Juan Fan^1,2, Jevin W. Zhang^1,2, Patrick P. Gao^1,2, Dan H. Sanes³, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, ³Center for Neural Science, New York University, New York, NY, United States

Binaural interaction is important for recognizing complex sound cues. This preliminary fMRI study probed such cortical modulation effect in the major auditory midbrain structure, inferior colliculus, in experimental rodents with unilateral primary AC ablation. BOLD response is significantly lower to binaural stimulation than to uniaural stimulation, and such decrease was more obvious in the right IC than in the left IC. These results provide further evidence of descending modulation of binaural interaction from AC. Further experiments will be pursued in normal animals and other auditory disorders to shine light on the understanding of cortical modulation of binaural midbrain sound processing.

João Jorge^1,2, Patrícia Figueiredo², Rolf Gruetter^1,3, and Wietske van der Zwaag^4
1Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Bioengineering, Instituto Superior Técnico, Lisbon, Portugal, ³Department of Radiology, University of Lausanne and University of Geneva, Lausanne, Switzerland, ⁴Biomedical Imaging Research Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Negative BOLD responses to stimulation are often found in various brain regions, and growing evidence supports their association with neuronal deactivation. The aim of this study was to characterize, in humans, positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation of varying contrast and duration, focusing on NBRs occurring in both visual and auditory cortical regions. Across subjects, visual PBRs and both visual and auditory NBRs were found to significantly depend on stimulus contrast and duration. Interestingly, for stimulation periods above 16s, visual and auditory NBRs tended to exhibit earlier returns to baseline than the visual PBR.

Normal Brain Spectroscopy

Monday 1 June 2015

Andrew Prescot¹, Xianfeng Shi², and Perry Renshaw^2,3
1Department of Radiology, University of Utah, Salt Lake City, UT, United States, ²Department of Psychiatry, University of Utah, Salt Lake City, UT, United States, ³VISN 19 MIRECC, Salt Lake City, UT, United States

Two-dimensional (2D) proton (¹H) magnetic resonance spectroscopy (MRS) techniques effectively enhance spectral resolution by separating metabolite resonances over a 2D surface. However, full uniform sampling (FUS) of the indirectly detected frequency dimension requires long measurement times thus rendering the methods unsuitable for many clinical applications. The present work investigates the combination of non-uniform sampling (NUS) strategies and iterative soft thresholding to reduce measurement times associated with 2D J-resolved ¹H MRS data acquired from human brain. A quantitative assessment of FUS and NUS situations is presented, and our preliminary data suggests that total measurement time can be reduced to 25%.

Hui Zhang¹ and Hao Lei^1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China

In this work, we measured metabolic profile in rat retrosplenial cortex (RSC) at preadolescence, adolescence and adulthood with in vivo 1H-MRS.We found that the changes for NAA, Tau, Ins and tPC levels were statistically significant across all three developmental ages. While the development-related changes of GABA, Glu and tCr levels were statistically significant only between adulthood and adolescence. The increased Glu and GABA levels from adolescence to adulthood, suggestive of that this developmental stage may be the critical period for the maturation of glutamatergic/GABAergic neurotransmission and/or dendritic stabilization in rat RSC

Hyeon-Man Baek^1,2, Youngjae Jeon¹, Jooyun Kim¹, Mirim Bang¹, Gyunggoo Cho¹, and Chaejoon Cheong^1
1Center for MR Research, Korea Basic Science Institute, Ochang, Chungbuk, Korea, ²Department of Bio-Analytical Science, University of Science & Technology, Yuseong-gu, Daejeon, Korea

In this study, in vivo 1H-MRS data and basis sets were acquired in-house on the same scanner. To test the performance of in-house basis sets, Cramer-Rao Lower Bounds (CRLB) were calculated. We also investigate how many and which metabolites can be reliably quantified in human prefrontal cortex using short-echo time (TE) 1H-MRS at 3T. LCModel with in-house basis sets reliably quantified 8 of 16 metabolites in the prefrontal cortex of healthy subjects at 3T. However, GABA and Tau showed relatively high CRLBs because these two peaks have low-concentration.This means that LCModel using in-house basis sets may be especially useful for short-TE and metabolites characterized by strongly coupled resonances, namely Ins, Glu, Gln, GSH, and Asp.

Chizuko Inui-Yamamoto^1,2, Tsuyoshi Shimura³, Izumi Ohzawa², and Yoshichika Yoshioka^1,2
1Laboratory of Biofunctional Imaging, WPI IFReC, Osaka University, Suita, Osaka, Japan, ²Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan,³Graduate School of Human Sciences, Osaka University, Suita, Osaka, Japan

The increases in the rBTs and neuronal activities in the IC are simultaneously induced by the intraoral stimulation. The intraoral stimulus-induced alterations in peak values of a chemical shift shown by MRS measurement indicate the changes in rBTs.

Anke Henning^1,2, Simone Grimm^3,4, Erich Seifritz³, and Milan Scheidegger^2,3
1Max Planck Institut for Biological Cybernetics, Tuebingen, Baden-Wuertemberg, Germany, ²Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Zurich, Switzerland, ³Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland, ⁴Clinic for Psychiatry and Psychotherapy, Charite Berlin, Berlin, Germany

In this work, we demonstrate that the cerebral Cho concentration is related to adaptive changes in neurotransmitter and more specifically glutamate secretion. To this we used the NMDA-receptor antagonist ketamine as a tool compound, which was previously shown by invasive methods to largely increase synaptic glutamate release.

Nicolaas AJ Puts^1,2, Stephanie Heba³, Ashley D. Harris^1,2, David J. McGonigle^4,5, C. John Evans⁵, Hubert Dinse⁶, Martin Tegenthoff³, Tobias Schmidt-Wilcke³, and Richard A. Edden^1,2
1Russell H. Morgan Dept. of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States, ²F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ³Dept. of Neurology, BG-klinikum Bergmannsheil, Ruhr - University, Bochum, Germany, ⁴School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom, ⁵CUBRIC/School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ⁶Neural Plasticity lab, Institute for Neuroinformatics, Ruhr - University Bochum, Bochum, Germany

Recent GABA MRS studies have shown links between brain GABA and behavior, brain activity, and disease. However, no studies to date have shown correlations in GABA concentration between regions, suggesting regional and functionally specificity. In this study, we measure GABA levels in left and right sensorimotor (SM1) cortex, two homologous regions known to be functionally connected. In two separate cohorts and sites, we found that GABA levels correlate significantly between left and right SM1. Although voxel tissue composition is highly correlated between sides, this does not explain significant variance in the GABA concentration or its bilateral correlation. This strongly supports the idea that individual differences in GABA reflect differences in tissue microstructure (e.g. density of GABAergic neurons) rather than bulk tissue properties. This work is important for understanding brain connectivity as well as brain plasticity.

Sanjeev Chawla¹, Yulin Ge¹, Hanzhang Lu², Olga Marshall¹, Ke Zhang¹, Brian J Soher³, and Oded Gonen^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ³Radiology, Duke University Medical Center, Durham, NC, United States

To ascertain the effect of mild hypercapnia (5%carbon dioxide) on whole brain N-acetylaspartate (WBNAA), and brain hemodynamics, twelve healthy male adults underwent non-localized whole-brain proton MR spectroscopy, T2-relaxation under spin tagging and pseudo continuous arterial spin labeling under both normocapnia and hypercapnia conditions. There was non-significant 0.2% change in WBNAA from normocapnia to hypercapnia condition. However, there was significant increase in global gray-matter cerebral blood flow (45.22±6.81 ml/100g/min vs 62.82±8.7 ml/100g/min) and venous oxygenation (56.31±7.33% vs 72.0±4.17%) from norcapnia to hypercapnia condition. Our study suggests that neuronal metabolism and vascular hemodynamics may have different response to mild hypercapnia.

Nicole D. Fichtner^1,2, Anke Henning^2,3, Niklaus Zoelch², Chris Boesch¹, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University Bern, Bern, Switzerland, ²Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

The upfield part of the spectrum has thus far been well-characterized using magnetic resonance spectroscopy; however, the downfield part at 5-10ppm remains less so, particularly in humans. This work aims to improve metabolite characterization by calculating the T₂’s of peaks downfield in grey matter at 7 T. We fitted downfield spectra to a heuristic model and obtained T₂’s for several peaks of interest; the T₂’s are all fairly similar, but significantly shorter than those reported for upfield peaks in the brain, which are approximately 70ms or longer depending on the structure.

Jeffrey A. Stanley¹, Ashley Burgess¹, Dalal Khatib¹, Karthik Ramaseshan¹, Noa Ofen¹, David R. Rosenberg¹, and Vaibhav A. Diwadkar^1
1Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, United States

Glutamate (Glu) plays a major role as an excitatory neurotransmitter in the hippocampus and the purpose of this study was to investigate whether Glu is modulated in the hippocampus during associative learning but not working memory (WM). Using ¹H fMRS study design, results provide the first ever evidence of neurochemical dynamics of the in vivo Glu signal in the hippocampus. Heightened hippocampal Glu signal was observed during associative learning followed by decreasing levels in response to learning proficiency. During the WM task, which is a predominantly PFC task, did not show any significant differences in hippocampal Glu compared to baseline.

Normal Aging Brain

Monday 1 June 2015

Thibo Billiet^1,2, Mathieu Vandenbulcke³, Burkhard Mädler^4,5, Ronald Peeters⁶, Thijs Dhollander^7,8, Hui Zhang⁹, Sabine Deprez^1,2, Bea RH Van den Bergh^10,11, Stefan Sunaert^1,2, and Louise Emsell^1,2
1Translational MRI, KU Leuven, Leuven, Belgium, ²Radiology, University Hospitals, Leuven, Belgium, ³Old Age Psychiatry, KU Leuven, Belgium, ⁴Philips Healthcare, Hamburg, Germany, ⁵Neurosurgery, University of Bonn, Bonn, Germany, ⁶University Hospitals, Leuven, Belgium, ⁷Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia, ⁸Elektrotechniek - ESAT, KU Leuven, Leuven, Belgium, ⁹Computer Science & Centre for Medical Image Computing, University College London, London, United Kingdom, ¹⁰Psychology, Tilburg University, Tilburg, Netherlands, ¹¹Health Psychology, KU Leuven, Leuven, Belgium

Using a combination of diffusion MRI (DTI/DKI/NODDI) and myelin water imaging, normal development of the brain can be assessed with increased specificity. This study explores signs of normal ageing between the age of 20 and 70.

Chandana Kodiweera¹, Andrew Alexander², and Yu-Chien Wu^3
1Dartmouth Brain Imaging Center, Dartmouth College, Hanover, NH, United States, ²Waisman Brain Imaging Lab, University of Wisconsin, Madison, Wisconsin, United States,³Center for Neuroimaging, Indiana University, Indianapolis, Indiana, United States

Fractional anisotropy (FA) may depend not only on the fiber orientation but also on the axonal density. In the case of a white matter disease, a change in either fiber orientation or axonal density will result a change in FA value. The orientation dispersion index and intra-cellular volume fraction, two tissue specific measures from NODDI model, can be used to study changes in fiber orientation and axonal density. In this study, aging data collected using a multiple shell acquisition scheme (HYDI) was analyzed using FA, odi and icvf to see how age and gender affect in these measures.

Muzamil Arshad^1,2, Jeffrey A. Stanley³, and Naftali Raz^4,5
1Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States, ²MD/PhD Program, Wayne State University School of Medicine, Detroit, MI, United States, ³Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, MI, United States, ⁴Psychology, Wayne State University, MI, United States, ⁵Institute of Gerontology, MI, United States

Age related reduction in myelin content of axons in white matter tracts connecting association cortices has been hypothesized as a potential substrate of age related cognitive decline in normal healthy aging. However, the most commonly used imaging methods to test this hypothesis are not specific to myelin content. Using multi-compartment T2 modeling we demonstrate Myelin Water Fraction Imaging is sensitive to age differences in myelin content in a healthy aging cohort.

Leonie Lampe^1,2, Alexander Schaefer^1,3, Christopher J. Steele¹, Katrin Arélin^1,2, Dominik Fritzsch⁴, Matthias L. Schroeter^1,2, Arno Villringer^1,2, and Pierre-Louis Bazin^1
1Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Leipzig Research Centre for Civilization Diseases & Clinic of Cognitive Neurology, University of Leipzig, Germany, ³Clinical Imaging Research Centre & Singapore Institute for Neurotechnology, National University of Singapore, Singapore, ⁴Department of Neuroradiology, University Hospital Leipzig, Germany

Here we adapted and validated a lesion segmentation algorithm previously aimed at MS lesions for white matter lesions (WML) segmentation within the general population. WML in the normal aging brain display diversity in pattern, intensity and extent. By means of iteratively re-normalising the contrast of the FLAIR images to better separate lesions from healthy tissue a dice coefficient of 0.63 was obtained. The validation was performed with 5 subjects with diverse lesions. The algorithm was applied to a large cohort study (age range 19-80 years) with approximately 1200 subjects.

PIN-YU CHEN^1,2, Yu-Ling Chang³, Yu-Jen Chen¹, Yu-Chun Lo¹, Yung-Chin Hsu¹, and Wen-Yih I Tseng^1,4
1Center For Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ²Department of Life Science, National Taiwan University, Taipei, Taiwan, Taiwan, ³Department of Psychology, National Taiwan University, Taipei, Taiwan, ⁴Molecular Imaging Center, National Taiwan University, Taiwan, Taiwan

Diffusion MRI is a powerful tool to probe the microstructural integrity of the white matter. This study used template-based diffusion spectrum imaging (DSI) tractography to analyze the microstructural integrity of 74 fiber tracts over the whole brain, and applied TFCW to evaluate the age effect on the tract integrity. Detailed investigation of the fiber tracts shows that the patterns of the white matter degeneration are heterogeneous. Our study supports some previous DTI literature that the microstructural integrity of the ageing brain decreases with age and the frontal part of the brain is the most severe region. In conclusion, our study provides detailed degenerative patterns of the white matter tracts in normal ageing which can serve as a useful reference for neurodegenerative diseases.

Shuzhong Chen¹, Vincent Mok², Yi-Xiang Wang¹, Ka Sing Wong², and Winnie CW Chu^1
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, ²Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

The apparent diffusion coefficient (ADC) is elevated and fractional anisotropy (FA) is reduced in age-related white matter changes (WMC) regions has been reported. This study is to determine the FA, relative anisotropy (RA), volume ration (VR) and ADC in the regions of WMC and the adjacent white matter tissue. A voxel expanded label map was created to detect the change of adjacent white matter tissue of the WMC regions. The FA, RA, VR and ADC shows progressively change as the region expands.

Jill Britt De Vis¹, Jaco J Zwanenburg¹, Jolanda M Spijkerman¹, Geert J Biessels¹, Jeroen Hendrikse¹, and Esben T Petersen^1
1University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

In this work we hypothesized that a fast and easy implementable volumetric cerebrospinal fluid (CSF) MRI sequence can be used as a surrogate for brain atrophy assessment. The obtained results were compared to clinically used atrophy rating scales and it was demonstrated that the CSF MRI sequence can be an alternative for brain atrophy assessment.

Marco Pagani^1,2, Debora Cutuli^3,4, Adam Liska¹, Paola Caporali^3,4, Daniela Laricchiuta^3,4, Francesca Foti^3,4, Cristina Neri⁴, Laura Petrosini⁴, and Alessandro Gozzi^1
1CNCS, Istituto Italiano di Tecnologia - IIT, Rovereto, TN, Italy, ²CIMeC - Center for Mind and Brain Sciences, UNITN - Università di Trento, Rovereto, TN, Italy, ³University “Sapienza”, Rome, Rome, Italy, ⁴Santa Lucia Foundation, Rome, Rome, Italy

Human studies have revealed a neuroprotective effect of omega-3 polyunsaturated acids (n-3 PUFA) in aging, with a positive correlation between peripheral n-3 PUFA levels and hippocampal volume. Consistently, higher dietary n-3 PUFA levels have been associated with delayed/reduced cognitive decline. To demonstrate a causal relationship between n-3 PUFA intake, cognition and brain morphology, we mapped gray-matter volume and recorded cognitive performance in aged mice upon 8-week-treatment with n-3 PUFA or control fatty acid. We show that n-3 PUFA treated-mice exhibit better cognitive performance and greater hippocampal and prefrontal volume, an effect that was strongly correlated with brain n-3 PUFA concentration.

Malgorzata Marjanska¹, J. Riley McCarten², Laura S Hemmy², Dinesh K Deelchand¹, and Melissa Terpstra^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Minneapolis VA Medical Center, Geriatric Research and Clinical Center, MN, United States

Oxidative stress occurs at an early stage of age related cognitive decline. Ascorbate (Asc, vitamin C) and glutathione (GSH) are key contributors to the antioxidant network. We utilized short echo time ¹H MRS at 7 T to reliably quantify these antioxidant concentrations in the aging brain in the occipital cortex and the posterior cingulate cortex, which is pertinent to the pathology of Alzheimer’s disease. Asc was higher and GSH lower in elder subjects in both brain regions. The Asc difference in the PCC were the most significant (p = 1.8 x 10^-5). This work has important implications for ongoing development of antioxidant based diagnosis, prevention and treatment of cognitive decline.

Bretta Russell-Schulz¹, Terri L Petkau², Blair R Leavitt^2,3, and Alex L MacKay^1,4
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²Centre for Molecular Medicine and Therapeutics, Child & Family Research Institute, Vancouver, BC, Canada, ³Medical Genetics, University of British Columbia, Vancouver, BC, Canada, ⁴Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada

Here we present ¹H-MRS results for the putamen over 6 years, 7 timepoints for healthy adult controls. There were no significant differences in the metabolite concentrations over the 7 visits, showing the validity of using these controls to compare to pathological data of the Huntington Disease over this timescale. The potential effects of age on metabolite concentration were also examined.

Karsten Mueller¹, Harald E Möller¹, Katrin Arelin^1,2, Jürgen Kratzsch³, Tobias Luck⁴, Steffi Riedel-Heller⁴, Arno Villringer^1,2, and Matthias L Schroeter^1,2
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Clinic for Cognitive Neurology, University of Leipzig, Germany, ³Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany, ⁴Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany

We investigated an interaction between plasticity processes, brain connectivity and healthy aging by measuring levels of serum BDNF and resting-state fMRI using eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in premotor and motor regions in elderly subjects in contrast to young subjects, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for elderly subjects. Our results might indicate that the amount of physical activity, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies.

Brittany Martinez¹, Jianli Wang¹, Prasanna Karunanayaka¹, Megha Vasavada², Paul J Eslinger³, and Qing X Yang^1,4
1Radiology, Penn State College of Medicine, Hershey, PA, United States, ²Neurology, UCLA, Los Angeles, CA, United States, ³Neurology, Penn State College of Medicine, Hershey, PA, United States, ⁴Neurosurgery, Penn State College of Medicine, Hershey, PA, United States

The purpose of this study was to quantitatively evaluate the effect of aging on olfactory system function using fMRI and to establish its relationship with olfactory behavior results. Younger and older subjects participated in an olfactory fMRI task and were asked to complete the UPSIT. Younger subjects had significantly greater activation in the POC and insula during odor conditions. Age was found to be negatively correlated with olfactory-related activation, while UPSIT scores were found to be positively correlated. The results support that olfactory fMRI is sensitive in the detection of age-related decline in olfactory function.

Wei Zhou^1,2, Eric R Muir^1,3, Jinqi Li¹, Crystal Franklin¹, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, United States, ²Radiology, University of Texas Health Science Center, San Antonio, Texas, United States, ³Ophthalmology, University of Texas Health Science Center, San Antonio, Texas, United States

The purpose of this study was to investigate the effects of age on retinotopic mapping measurements with a relatively wide view to include central and periphery vision areas. By setting up wide-view checkboard stimulation, the boundaries of visual fields were defined. Our results demonstrated that central visual areas of older subjects exhibited weaker BOLD responses for central stimulation (0°~45°) but stronger BOLD responses for periphery stimulation (45°~90°), compared to younger subjects. These findings indicated there are central vision loss and neural reorganization with age.

Toshiharu Nakai¹, Ayuko Tanaka¹, Mitsunobu Kunimi¹, Sachiko Kiyama¹, and Annabel SH Chen^2
1Neuroimaging & Neuroinformatics, National Center for Geriatrics and Gerontology, Ohbu, Aichi, Japan, ²Division of Psychology, School of Humanities and Social Sciences, Nanyang Technological University, Singapore, Singapore

In order to establish a classification of elderly with potential cognitive decline, we investigated the effect of introducing behavioral performance on extracting age-related change from resting state network (RSN) activities. Two types of covariates derived from one goal-oriented operation, but representing different steps were employed. The age-related change was differently affected in the anterior part of default mode network depending on the covariate, while such change was not observed in its posterior part. It may be suggesting that classification of RSN activities in elderly may be related to the performance level of the subjects.

Xueli Wang¹, Jin Xu¹, XiuFen Zhang¹, Xiaolong Peng¹, and Pan Lin^1
1Institute of Biomedical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

Default mode network(DMN) plays an important role in neural cognitive research. Previous studies have suggested that functional connectivity of DMN will decrease with age, which may also cause cognitive decline. However, there is still lack of studies on age-related changes in default mode sub-networks such as anterior default mode network (aDMN) and posterior default mode network (pDMN). The aim of this study was to investigate the age-related effects on functional connectivity between aDMN and pDMN during resting state.

Jack Knight-Scott^1
1Radiology, Children's Healthcare of Atlanta, Atlanta, Georgia, United States

Based on age-related differences in the response of animals to experimentally-induced water intoxication, we hypothesize that the degree of tissue swelling is an intrinsic, age-dependent property of brain tissue that we have named the expansion capacity, . The expansion capacity is a measure of the capability of tissue to accomodate osmotically induced volume increases in the CNS. This includes the effects of the osmotic regulatory systems (both local and systemic) and the biomechanical properties of the tissue. Here we introduce the basic concept of the expansion capacity and attempts to measure it in a group of healthy adults.

Thomas Walker¹, Christos Michaelides¹, Harry Parkes², William Crum¹, Tina Geraki³, Amy Herlihy⁴, and Po-Wah So^1
1Department of Neuroimaging, Institute Of Psychiatry, King's College London, London, United Kingdom, ²CR-UK, Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, United Kingdom, ³Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, United Kingdom, ⁴Agilent Technologies, Yarnton, Oxfordshire, United Kingdom

Brain iron accumulation with ageing may play a role in senescent processes, with age-related increases in basal ganglia R2 and R2* observed in man and associated with increased iron. Here, we show similar increases in R2 and R2* in the basal ganglia of ageing C57BL/6J mice. Quantitatively measured increased iron by synchrotron radiation X-ray fluorescence elemental iron mapping suggests the increased R2 and R2* values may indeed arise from higher iron concentrations. Thus, iron dyshomeostasis may play a role in ageing and MR relaxometry may be used to monitor these ageing processes.

Adam G Thomas^1,2, Andrea Dennis², Nancy B Rawlings², Charlotte J Stagg², Helen Dawes³, Heidi Johansen-Berg², and Peter A Bandettini^1
1NIMH, Bethesda, MD, United States, ²FMRIB, University of Oxford, Oxford, United Kingdom, ³Movement Sciences Group, Oxford Brookes University, Oxford, United Kingdom

Susceptibility shows a positive correlation with fitness measures.

Lukas Pirpamer¹, Edith Hofer¹, Paul Freudenberger², Stephan Seiler¹, Christian Langkammer³, Franz Fazekas¹, Stefan Ropele¹, and Reinhold Schmidt^1
1Department of Neurology, Medical University of Graz, Graz, Styria, Austria, ²Molecular Biology and Biochemistry, Medical University of Graz, Styria, Austria, ³MGH/HST Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, United States

This study analyzed R2* relaxomentry data from 314 healthy volunteers in various gray matter regions of the brain with the goal to find determinants for brain-iron accumulation. 18 factors were analyzed, which were related to lifestyle, cerebrovascular risk factors, serum levels of iron and iron-associated gene-snips. BMI seemed to be the most relevant determinant for increased R2* values, especially in the hippocampus. This finding stands in line with the hypothesis that BMI is an independent risk factor for dementia.

Valerie C. Anderson¹, Manoj K. Sammi¹, Yosef A. Berlow¹, Jeffrey A. Kaye², Joseph F. Quinn², and William D. Rooney^1
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Department of Neurology, Oregon Health & Science University, Portland, OR, United States

Brain iron concentration, [Fe], was quantified in 20 healthy subjects (63  9 yrs) based on 7T ¹H₂O R₁ and R₂ measurements and relaxivity models that incorporate terms for both macromolecular volume fraction and [Fe]. Pial surface iron maps were prepared and the extent and spatial distribution of iron in 6 functional networks was determined. We find that [Fe] varies throughout the cortex in older individuals and is highest in frontoparietal and default networks. These findings suggest that the vulnerability of age-related changes in these networks may be related to increased iron content.

Brain Resting State & Default Mode Network

Monday 1 June 2015

Vesa Kiviniemi¹, Xindi Wang², Vesa Korhonen¹, Tuija Keinänen³, Yu-Feng Zang⁴, Pierre LeVan⁵, and Shella Keilholz^6
1Diagnostic Radiology, MRC, Oulu University Hospital, Oulu, Oulu, Finland, ²Beijing Normal University, Beijing, China, ³Clinical Neurophysiology, MRC, Oulu University Hospital, Oulu, Oulu, Finland, ⁴Hangzhou Normal University, Hangzhou, China, ⁵University of Freiburg, Freiburg, Germany, ⁶Emory University, Atlanta, Georgia, United States

We imaged whole brain with magnetic resonance encpehalography using a 100 ms TR under-sampled k-space trajectory. This critical sampling enabled separation of cardiac pulse and respiratory effects from very low frequency BOLD signal sources. We show that physiological noise has a unique spatiotemporal patterns of noise propagation pattern throughout the brain. The results suggest that conventional averaged external estimates of physiological noise need to be replaced by critically sampled brain data.

Timo De Bondt^1,2, Dirk Smeets³, Pim Pullens^4,5, Wim Van Hecke³, Yves Jacquemyn^6,7, and Paul M Parizel^4,5
1Radiology, Antwerp University Hospital, Antwerp, Antwerp, Belgium, ²Radiology, University of Antwerp, Antwerp, Antwerp, Belgium, ³icoMetrix, Leuven, Belgium, ⁴Radiology, Antwerp University Hospital, Antwerp, Belgium, ⁵Radiology, University of Antwerp, Antwerp, Belgium, ⁶Gynaecology and Obstaetrics, Antwerp University Hospital, Antwerp, Belgium, ⁷Gynaecology and Obstaetrics, University of Antwerp, Antwerp, Belgium

Resting-state fMRI images were acquired in 18 women with natural menstrual cycle (NC) during the follicular phase. 19 Subjects using hormonal contraception (HC) were scanned during pill free week and during pill intake. Data were analyzed with spatially constrained ICA. We show long term alterations in bilateral cingulate gyrus due to HC use and short term effects in bilateral insula. Our results support previous, non-resting-state fMRI-based, literature. Importantly, HC-use is never corrected for in this and other MRI-subfields. Consequently, researchers introduce heterogeneity in their data, which will lead to loss of accuracy and precision.

Oleksii Omelchenko¹ and Zinayida Rozhkova^2
1Human and Animal Physiology, Taras Shevchenko National University of Kyiv, Kyiv, Kyiv, Ukraine, ²Radiology, Medical Clinic BORIS, Kyiv, Ukraine

Some regions of DMN remain active during the task execution. We propose TID and functional connectivity analysis under the execution of motor tasks with various complexities for DMN heterogeneity study. Motor task fMRI was done for DMN deactivation and connectivity analysis. Despite the unified pattern of brain activation across different motor tasks, deactivation pattern differ depending on the complexity of the movements and their cognitive demand. Nodes of DMN may function simultaneously in the TID and task independent regimes during the movements. Obligatory PCC involvement in TID and task independent patterns of DMN functioning supports its possible ‘hub’ function.

Hong Gu¹, Yuzheng Hu¹, Xi Chen¹, and Yihong Yang^1
1National Institute on Drug Abuse, NIH, Baltimore, MD, United States

The coupling between the salience network (SN) and the default mode network (assessed by the SN-PCC connectivity) was negatively correlated with the regional excitation and inhibition balance (expressed as ratio of glutamate over GABA R_Glu/GABA) in PCC. Both of the SN-PCC connectivity and the R_Glu/GABA predicted the working memory task-induced deactivation in the PCC. The mediation analysis showed the relationship between the SN-PCC coupling and PCC deactivation was completely mediated by the local balance of the excitation and inhibition R_Glu/GABA.

Don Marciel Ragot^1,2, Erin Mazerolle³, and J. Jean Chen^1,4
1Rotman Research Institute, Baycrest, Toronto, Ontario, Canada, ²Engineering Science, University of Toronto, Ontario, Canada, ³University of Calgary, Ontario, Canada,⁴Medical Biophysics, University of Toronto, Ontario, Canada

Recent studies have used BOLD to detect white-matter functional activation in the largest white matter structures in the brain while subjects are performing interhemispheric tasks. While these studies lay the foundation for white-matter fMRI, they also used custom acquisition techniques unavailable on most scanners. Also, they report focal brain activity, but do not assess functional connectivity. In this work, we investigate the feasibility of detecting white-matter activation using conventional gradient- or spin-echo EPI at 3 Tesla. Spin-echo EPI produced robust white-matter activation in the corpus callosum, but not gradient-echo. We also demonstrate task-related white-matter fMRI connectivity using spin-echo EPI.

Ricardo Ribeiro¹, Inês Neiva¹, and Hugo Alexandre Ferreira^1
1Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisboa, ., Portugal

An application for visualizing brain connectivity data was developed based on a virtual reality (VR) head-mounted display and a gesture recognition (GR) human-computer interface. The application makes uses of volumetric T1-weighted data and connectivity matrices (structural, functional or effective) to compute a brain graph that is superimposed on corresponding brain anatomy. Additionally, the application can import both imaging and connectivity metrics. The VR application is able to create an immersive experience in which the user can navigate outside and inside the brain graph and visualize global or region-specific imaging and connectivity metrics using nothing more than his/hers own gestures.

Karolina J Urban^1,2, Karen M Barlow^3,4, Laronna Sewell², Bradley G Goodyear^1,5, and Jeff F Dunn^1,5
1Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ²Neurosciences, University of Calgary, Calgary, Alberta, Canada, ³Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, ⁴Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada, ⁵Radiology, University of Calgary, Calgary, Alberta, Canada

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Zhixin Li¹, Chenxuan Li², and Christopher P Pawela^2,3
1Plastic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Plastic Surgery, Medical College of Wisconsin, Wisconsin, United States, ³Biophysics, Medical College of Wisconsin, Wisconsin, United States

was to reveal the region-specific effects of genetic differences between two inbred rat strains, Brown Norway (BN) and Dahl salt-sensitive (SS/Mcwi), on a biologic measure in brain using BOLD-fMRI under a well-established task paradigm

Won-Jin Moon¹, Hyeong Su An², Jae-Kyun Ryu³, Ju Yeon Park⁴, Won Sung Yun⁴, Jin Woo Choi⁴, Geon-Ho Jahng⁵, and Jang-Yeon Park^6
1Department of Radiology, Konkuk University School of Medicine, Seoul, Seoul, Korea, ²1. Department of Radiology, Konkuk University School of Medicine, Seoul, Korea, ³2. Department of Biomedical Engineering, Konkuk University, Seoul, Korea, ⁴Konkuk University School of Medicine, Seoul, Korea, ⁵Kyunghee University, Seoul, Korea, ⁶Konkuk University, Seoul, Korea

This study evaluated inter-vender reliability and inter-session reliability of rsfMRI by using temporal signal-to-noise ratio (tSNR) and connectivity of default-mode network (DMN).Although tSNR of rsfMRI was relatively good-to-excellent on three different 3-T MRI (from three different venders) on two different occasions, some inter-vender and inter-session differences in connectivity of the DMN were observed. Therefore, researchers using rsfMRI should be aware of these limitations especially in case of longitudinally designed multicenter studies.

Kayako Matsuo¹, Katsuaki Suzuki¹, Keisuke Wakusawa², Kiyokazu Takebayashi¹, Yasuo Takehara³, and Norio Mori^1
1Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan, ²Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan, ³Department of Radiology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

Task-induced deactivation (TID) is recently a focus of fMRI research. It typically demonstrates maps of the default mode network, showing relevance to cognitive impairments. We investigated the changes of the TID in the medial structures using visual, visuomotor and counting tasks and the combination of the tasks. Demands for cognitive processing affected the medial prefrontal cortex, whereas task types modulated the posterior cingulate cortex (PCC) and the precuneus. Hand action reduced the TID of the area adjacent to the parieto-occipital sulcus, which included the region frequently used as a “seed” in functional connectivity analyses of resting-state fMRI.

Hanbing Lu¹, Julia K Brynildsen¹, Li-Ming Hsu¹, Thomas Ross¹, Elliot A Stein¹, and Yihong Yang^1
1Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, United States

Proper choice of anesthetics is of critical importance for the success of an fMRI experiment. An anesthetic regime that uses low dose of dexmedetomidine in combination with low dose of isoflurane, permitted fMRI data acquisition for several hours. The rat default mode brain network has been successfully identified with this preparation, indicating that this protocol minimally disturbs brain network functions. However, medetomidine is known to cause peripheral vasoconstriction, respiratory suppression and bradycardia, confounding the fMRI signal. The goal of this study is to systematically characterize and to optimize physiological conditions for fMRI experiment under this anesthetic regimen.

Mood Disorders & Psychosis

Monday 1 June 2015

Arron W.S. Metcalfe¹, Benjamin I. Goldstein^2,3, David E. Crane¹, Antonette Scavone³, Hanzhang Lu⁴, and Bradley J. MacIntosh^5,6
1Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada, ²Psychiatry & Pharmacology, University of Toronto, Ontario, Canada, ³Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, ⁴University of Texas Southwestern Medical Center, Dallas, Texas, United States, ⁵Department of Medical Biophysics, University of Toronto, Ontario, Canada, ⁶Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada

Bipolar disorder (BD) is associated with both increased cardiovascular disease (CVD) risk and medial-frontal cortex dysfunction. Potential interaction between oxygen availability and blood oxygen level dependent (BOLD) signal during motor-inhibition was examined in BDs and healthy controls. Base-rate cerebral venous oxygen availability (Yv) was analyzed as a covariate. Yv group means were similar. Lower Yv should be associated with larger potential increase in task signal and this was supported in distributed regions for both groups. Importantly, a positive relationship emerged in task related medial cortex only for BDs, possibly suggesting dampened vascular response. Overall, model corrections for Yv were modest.

Leif Oltedal^1,2, Ute Kessler^1,3, Nathan S White⁴, Hauke Bartsch⁵, Bjarne Hansen³, Lars Ersland⁶, Renate Grüner², Joshua Kuperman⁴, Dominic Holland⁷, Kenneth Hugdahl^3,8, Ketil J Ødegaard^1,3, and Anders M Dale^4,5
1Department of Clinical Medicine, University of Bergen, Bergen, Norway, ²Department of Radiology, Haukeland University Hospital, Bergen, Norway, ³Division of Psychiatry, Haukeland University Hospital, Bergen, Norway, ⁴Department of Radiology, University of California, San Diego, California, United States, ⁵Multi-Modal Imaging Laboratory, University of California, San Diego, California, United States, ⁶Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway, ⁷Department of Neurosciences, University of California, San Diego, California, United States, ⁸Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway

Electroconvulsive therapy (ECT) is by many clinicians regarded as the most effective acute treatment of major depressive disorder. At the group level, ECT has been shown to induce structural changes in the hippocampus, supporting a neurotrophic hypothesis. Here we demonstrate that ECT-induced structural changes may be appreciated at the level of the individual patient after appropriate preprocessing and co-registration of longitudinal intra-individual images. At the group level (n=6; 3D T1 volumes at 3 time points) quantification with FreeSurfer and Quarc, suggests structural changes in various ROIs in the subcortical gray matter, in addition to the hippocampus.

Joanes Grandjean¹, Damiano Azzinnari², Aline Seuwen¹, Erich Seifritz², Christopher Pryce², and Markus Rudin^3,4
1Institute for Biomedical Engineering, ETH and University Zurich, Zurich, Switzerland, ²Psychiatric University Hospital Zurich, Zurich, Switzerland, ³Institute for Biomedical Engineering, ETH and University Zurich, Zurich, Select, Switzerland, ⁴Institute of Pharmacology and Toxicology, University Zurich, Zurich, Switzerland

A chronic social defeat (CSD) mouse model has demonstrated that chronic social stress induces depression-relevant behavior as well as changes related to the immune and dopamine systems. We have characterized the functional, metabolic, and structural changes occurring in mice following CSD using fMRI/MRS/MRI. We report alterations in the functional networks, in particular in the cingulate and prefrontal cortex. Fractional anisotropy was increased in the cingulum fibers of CSD mice compared to controls. Finally, inositol concentration was increased in the CSD mice. These reports compare well reports of functional alteration in the default mode network in humans with depressive disorders.

Zan Wang¹, Yonggui Yuan², Hao Shu¹, Feng Bai¹, Jiayong You³, and Zhijun Zhang^1
1Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, Jiangsu, China, ²Psychosomatics and Psychiatry, Affiliated ZhongDa Hospital of Southeast University, Nanjing, Jiangsu, China, ³Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China

Altered topographical organization of the default-mode network in first-episode remitted geriatric depression.

Casey P. Johnson¹, Lois A. Warren², Gary E. Christensen³, Jess G. Fiedorowicz², Vincent A. Magnotta¹, and John A. Wemmie^2,4
1Radiology, University of Iowa, Iowa City, IA, United States, ²Psychiatry, University of Iowa, Iowa City, IA, United States, ³Electrical and Computer Engineering, University of Iowa, Iowa City, IA, United States, ⁴Veterans Affairs Medical Center, Iowa City, IA, United States

Bipolar disorder is characterized by episodes of depressed and manic mood states. Little is known about what triggers and perpetuates these moods. We applied a new technique to study mood states in bipolar disorder: whole-brain quantitative T1ρ mapping. Average T1ρ maps were compared between groups of 9 depressed, 15 euthymic, 11 manic, and 25 control participants. Cerebellar T1ρ values were abnormally elevated in all three mood states compared to controls. Furthermore, putamen T1ρ values were reduced in depression compared to euthymia and controls. These findings point to both trait and mood-state-dependent abnormalities in bipolar disorder, possibly due to abnormal metabolism.

bian haiman¹, ji shengzhang², zhuo chunjun³, li gongying⁴, and ren junjie^2
1the Fourth Central Hospital of Tianjin, tianjin, tianjin, China, ²the Fourth Central Hospital of Tianjin, tianjin, China, ³Tianjin Anning Hospital, tianjin, China, ⁴Department of psychiatry, Jining Medical University, shandong, China

If negative stressful life events (NSLEs), such as bereavement, accidental disasters play a key role in the onset and maintenance of depression?Our experiment adopted a block pattern design and use a 3.0 T MRI system to obtain the fMRI data. Our study found that drug-naïve female patients with their first major depressive episode who had experienced NSLEs prior to the onset of depression had abnormal activation of several brain regions involved in emotional perception, memory, evaluation, and regulation.These results were consistent with the negative cognitive theory of depression, which proposes that negative stimulation is an important factor in the onset and maintenance of depression.

Harald Kugel¹, Udo Dannlowski^2,3, Dominik Grotegerd², Ronny Redlich², Janina Suchy², Nils Opel², Thomas Suslow^2,4, Carsten Konrad³, Patricia Ohrmann², Jochen Bauer², Tilo Kircher³, Axel Krug³, Andreas Jansen³, Bernhard T Baune⁵, Walter Heindel¹, Katharina Domschke⁶, Volker Arolt², Christa Hohoff², Marcella Rietschel⁷, and Stephanie H Witt^7
1Department of Clinical Radiology, University of Münster, Muenster, NRW, Germany, ²Department of Psychiatry, University of Münster, Muenster, NRW, Germany,³Department of Psychiatry, University of Marburg, Marburg, HE, Germany, ⁴Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, SN, Germany, ⁵Discipline of Psychiatry, University of Adelaide School of Medicine, Adelaide, SA, Australia, ⁶Department of Psychiatry, University of Würzburg, Würzburg, BY, Germany, ⁷Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, BW, Germany

Neurocan (NCAN) rs1064395 genotype is associated with psychiatric disorders as major depression, schizophrenia, and bipolar disorder. In risk allele (A) carriers, compared to carriers of the non-risk allele G, voxel based morphometry (VBM) revealed reduced gray matter volume in hippocampus and amygdala, in healthy volunteers as well as in major depression patients. We conclude that the increased risk for psychiatric disorder may be mediated by structural deficits in amygdala and hippocampus.

Hu Cheng¹, Rui Yang², Hongbo Zhang², Xiaoping Wu², Junle Yang², Mingyue Ma², Yanjun Gao², Hongsheng Liu², and Shengbin Li^2
1Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States, ²Xi’an Jiaotong University, Xi'an, Shanxi, China

In this study, we combined Independent Component Analysis (ICA) and seed based connectivity analysis to study the posterior DMN network between patients and normal controls, as well as pre-treatment and post-treatment conditions. Our results showed significant difference of the posterior default mode sub-network between major depression patients and normal controls. Specifically, normal controls exhibited higher connectivity between PCC and frontal/temporal regions. The treatment does improve the connectivity strength of patients, especially in the anti-correlated network. These differences were unlikely induced by difference in head motion.

SENTHIL S KUMARAN¹, BHOOMIKA R KAR², SUNITA GUDWANI¹, and ANKEETA SHARMA^1
1DEPARTMENT OF NMR AND MRI FACILITY, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, New Delhi, Delhi, India, ²Centre of Behavioural and Cognitive Sciences, UNIVERSITY OF ALLAHABAD, Allahabad, Uttar Pradesh, India

In today’s world of stress induced impairments regulation of the emotions is essential demand. The demands comparative to habits need selective attention, planning, response suppression and response selection for decision making. A central interest in the study of emotions is the interplay between emotional expressions, inhibitions and cognitive regulations. There is little corresponding literature on facial emotion perception so the study was planned to observe the interference and inhibition during facial (happy, sad and neutral) expressions. The results indicate that suppression of automatic action in favor of controlled less automatic facial expression required higher order visual processing system including occipito-temporal-parietal neural pathway.

Subechhya Pradhan¹, Joseph S Gillen^1,2, S. Andrea Wijtenburg³, Ashley D Harris¹, Laura M Rowland³, and Peter B Barker^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²Kennedy Krieger Institute, Baltimore, Maryland, United States, ³Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States

MR spectroscopy is an important tool for the non-invasive measurement of brain metabolite levels in various neuropsychiatric disorders. Knowledge of the reproducibility of metabolite measurements in patients is important in studying metabolite changes due to disease progression and/or treatment. In this study, we assess the 1-week reproducibility of the metabolite concentration measurements made at 7 Tesla using the semi-LASER and STEAM sequences, in a cohort of subjects with stable, chronic schizophrenia.

Ekkehard Küstermann¹, Vani Thimmashetty¹, Jannis Gundelach², and Lena Wischhof^2
1"In-vivo-MR" AG, FB2, Universität Bremen, Bremen, Bremen, Germany, ²Department of Neuropharmacology, Brain Research Institute, University of Bremen, Bremen, Bremen, Germany

Maternal exposure to infection during mid-gestation increases the risk for the offspring to develop schizophrenia. Resting-state fMRI was performed with adult rats from the offspring and analysed by ICA. The average power spectrum over all estimated ICs collected from the entire brain was calculated and revealed highly condition specific characteristics. The observed differences of these signals may reflect altered network connectivities in the offspring. Our study supports the notion that rsfMRI provides an attractive tool for defining biomarkers of neuropsychiatric disorders in preclinical animal models as it is non-invasive, undemanding and limited in scanning time.

Anxiety & PTSD

Monday 1 June 2015

D Rangaprakash¹, Gopikrishna Deshpande^1,2, D Narayana Dutt³, Thomas A Daniel², Adam Goodman², Jeffrey S Katz^1,2, Nouha Salibi^1,4, Thomas S Denney Jr^1,2, and MAJ Michael N Dretsch^5,6
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Department of Psychology, Auburn University, Auburn, AL, United States, ³Department of Medical Electronics, Dayananda Sagar College of Engineering, Bangalore, Karnataka, India, ⁴MR R&D, Siemens Healthcare, Malvern, PA, United States, ⁵National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States, ⁶U.S. Army Aeromedical Research Laboratory, Fort Rucker, AL, United States

Global characterization of functional segregation and integration were obtained by estimating transitivity and global efficiency values from directional connectivity networks obtained from resting state fMRI data acquired in Soldiers with PTSD, with both post-concussion syndrome (PCS) and PTSD, and matched military controls. These measures were higher in controls compared to both PTSD and PCS+PTSD groups, suggesting abnormalities in functionally specialized modular structures as well as integration between such units in PTSD. However no significant differences were found between PTSD and PCS+PTSD groups, suggesting that there is localized impact on only certain brain regions in individuals with PCS.

Yawen Sun¹, Yan Zhou¹, Wang Zhen², Zhenyu Zhou³, Yong Zhang³, Jieqing Wan⁴, and Jianrong Xu^1
1Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, China, ²Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³GE Healthcare, Shanghai, China, ⁴Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

In this manuscript, we report the current study to identify the possible alteration in inter-hemispheric interactions in trauma-exposed victims who went on to develop PTSD before diagnosis using resting-state fMRI and diffusion tractography techniques. The victims with PTSD exhibited an abnormal homotopic pattern with decreased voxel-mirrored homotopic connectivity (VMHC) in the superior/middle frontal gyrus before diagnosis. Structural connectivity changes were in accordance with the alterations in functional connectivity in corpus callosum genu. Our results may be potential markers showing predisposition towards developing PTSD.

Fawzi Boumezbeur¹, Riccardo Magalhães², Ashley Novais², Sébastien Mériaux¹, Michel Bottlaender¹, Arnaud Cachia³, Thérèze Jay³, and Nuno Sousa^2
1NeuroSpin, DSV/I2BM, Commissariat à l'Energie Atomique, Gif-sur-Yvette, France, ²ICVS/3B's-PT, School of Health Sciences, University of Minho, Braga, Portugal, ³Inserm U894, Center for Psychiatry and Neurosciences, University Paris-Descartes, Paris, France

In this study, stress-induced neurochemical alterations were explored in the hippocampus of chronically stressed rats using in vivo ¹H MRS at 11.7 T; concomitantly potential correlations with the plasma level of corticosterone as a biomarker of stress were investigated. Our observations are consistent with a moderate neuronal metabolic stress (NAA: -3%) and the up-regulation of GABAergic neurotransmission (GABA: +14%) to limit the HPA axis hyperactivation due to our 3 week-long chronic stress paradigm. Notably, resilience to longitudinal stress (i.e. low corticosterone) in stressed rats is associated to a likely “neuroprotective” glial activity (Glu/Gln: -27% and Ins: +7%).

Raquel Phillips¹, Vadim Zotev¹, Kymberly Young¹, Chung Ki Wong¹, Brent Wurfel¹, Matthew Meyer^1,2, Frank Krueger^1,3, Matthew Feldner^1,4, and Jerzy Bodurka^1,5
1Laureate Institute for Brain Research, Tulsa, OK, United States, ²Laureate Psychiatric Clinic and Hospital, Tulsa, OK, United States, ³Dept. of Psychology, George Mason University, Fairfax, VA, United States, ⁴Dept. of Psychological Science, University of Arkansas, Fayetteville, AR, United States, ⁵College of Engineering, University of Oklahoma, Tulsa, OK, United States

We performed emotion regulation training in veterans with combat-related PTSD using real-time fMRI neurofeedback (rtfMRI-nf). Seven subjects in the experimental group learned to upregulate left amygdala activity using rtfMRI-nf based on retrieval of happy autobiographical memories, while seven subjects in the control group performed the rtfMRI-nf task with feedback from the left horizontal segment of the intraparietal sulcus. Functional connectivity analysis showed that for the experimental group activity in the left amygdala was more correlated with other regions of the brain during positive memory recall following three sessions of neurofeedback than it was in the control group.

Simon Schwab¹, Leila M Soravia¹, Yosuke Morishima^1,2, Masahito Nakataki^1,3, Thomas Dierks¹, Thomas E Nichols⁴, and Andrea Federspiel^1
1Dept. of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Bern, Switzerland, ²Japan Science and Technology Agency, PRESTO, Japan,³Department of Psychiatry, The University of Tokushima, Tokushima, Japan, ⁴Department of Statistics & WMG, University of Warwick, Coventry, United Kingdom

In the present work we presented spider pictures during an event-related fMRI experiment to nine patients with spider phobia. We implemented multivoxel pattern analysis (MVPA) using the searchlight procedure, and a Gaussian Naive Bayes classifier to decode brain areas predicting phobic content. We found significant positive classification accuracies across subjects in the cingulate gyrus, the insula, and the postcentral gyrus. A region in the middle cingulate gyrus demonstrated the highest mean classification accuarcy across subjects. Thus, the present study shows that MVPA seems to be a sensitive approach to find brain areas predicting phobic content.

Gwang-Won Kim¹, Jong-Chul Yang², and Gwang-Woo Jeong^1,3
1Research Institute of Medical Imaging, Chonnam National University Medical School, Gwang-ju, Korea, ²Psychiatry, Chonbuk National University Hospital, Jeong-ju, Korea,³Department of Radiology, Chonnam National University Medical School, Gwang-ju, Korea

Patients with obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD) are associated with abnormalities in the processing and regulation of anxiety as well as cognitive deficits. The purpose of this study was to discriminate the brain activation patterns associated with the anxiety-provoking distracter during the working memory (WM) maintenance for the human faces between patients with OCD and GAD, and healthy controls by using a function magnetic resonance imaging (fMRI).

Chung-Man Moon¹ and Gwang-Woo Jeong^1,2
1Radiology, Research Institute for Medical Imaging, Gwangju, Gwangju, Korea, ²Radiology, Chonnam National University Hospital, Chonnam Natioanl University Medical School, Gwangju, Korea

Generalized anxiety disorder (GAD) is characterized by excessive, pervasive and uncontrollable anxiety in daily life. Recent studies demonstrated that the symptoms of GAD are associated with neural dysfunction related with cognition and emotional regulation. However, it is unclear how the white matter (WM) volume and cerebral metabolites are associated with the typical symptoms of GAD without other comorbid psychiatric disorders. The purpose of this study was to investigate the abnormalities in WM volumes and cerebral metabolite concentrations in patients with GAD using the voxel-based morphometry (VBM) and localized 1H-MR spectroscopy (1H-MRS).

Wenjing Zhang¹, Xun Yang¹, Su Lui¹, Yajing Meng², Li Yao¹, Yuan Xiao¹, Wei Zhang², and Qiyong Gong^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, China

A multivariate pattern analysis was used to characterize local coherence of fMRI bold signals implicated in individuals with social anxiety disorder (SAD). By identifying the inter-group differences in whole brain ReHo pattern with high classification accuracy at the individual level, the present study suggests local connectivity and synchronization extracted from fMRI bold signal could be a potential biomarker to identify SAD patients. On this condition, future studies with the integration of ReHo with other different imaging modality measurements may give a better insight into the imaging biomarkers of the condition.

Shin-Eui Park¹ and Gwang-Woo Jeong^1,2
1Interdisciplinary Program of Biomedical Engineering, Chonnam National University, Gwangju, Jeollanamdo, Korea, ²Department of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea

this study utilized 1H MRS and VBM analysis to investigate the brain volume and metabolite changes in the patients with OCD.

Vadim Zotev¹, Raquel Phillips¹, Masaya Misaki¹, Chung Ki Wong¹, Brent Wurfel¹, Matthew Meyer^1,2, Frank Krueger^1,3, Matthew Feldner^1,4, and Jerzy Bodurka^1,5
1Laureate Institute for Brain Research, Tulsa, OK, United States, ²Laureate Psychiatric Clinic and Hospital, Tulsa, OK, United States, ³Neuroscience Dept., George Mason University, Fairfax, VA, United States, ⁴Dept. of Psychological Science, University of Arkansas, Fayetteville, AR, United States, ⁵College of Engineering, University of Oklahoma, Tulsa, OK, United States

We have performed emotion regulation training in veterans with combat-related PTSD using real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG. Six PTSD patients learned to upregulate their left amygdala activity using rtfMRI-nf during a positive emotion induction task based on retrieval of happy autobiographical memories. We observed task-dependent variations in frontal EEG asymmetry (FEA) in the upper alpha band that correlated with PTSD severity (CAPS). Individual changes in CAPS ratings significantly correlated with changes in FEA variations. The results suggest that variations in FEA during rtfMRI-nf training may provide a sensitive measure of PTSD severity and individual response to treatment.

Subash Khushu¹, Shilpi Modi¹, Poonam Rana¹, and Richa Trivedi^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, Delhi, India

Trait anxiety affects brain functioning and cognition as suggested by various neuroimaging and behavioural studies. In order to identify individuals that are at risk for the development of clinical anxiety disorders and depression, identifying hallmarks of trait anxiety becomes important, to fascilitate timely preventive interventions. Based on our invivo 1H MRS and diffusion tensor Tractography findings we suggest that the alterations in neurometabolite levels in Anterior Cingulate Cortex and strength of the two major white matter fibres of the limbic system namely uncinate fasciculus and fornix, in relation with the trait anxiety levels may be possible markers of trait anxiety.

Ahmad Raza Khan¹, Andrey Chuhutin¹, Brian Hansen¹, Ove Wiborg², Christopher D Kroenke³, and Sune Nørhøj Jespersen^1
1Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark, ²Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark,³Advanced Imaging Research Center, Oregon Health & Science University, Beaverton, Oregon, United States

CMS is one of the leading causes of depression, but the underlying pathology can be verified only by microscopy. This study was performed on CMS model of rat to explore sensitivity of diffusion weighted MRI to microstructural alterations in different brain regions. We utilized biophysical modelling and diffusion kurtosis (DKI) imaging to characterize microstructural aberrations in CMS brains. The study reveals significant increases in neurite density and mean kurtosis, and significant decreases in MD and extracellular diffusivity in the prefrontal cortex. We conclude that biophysical modelling and DKI modalities are able to detect preclinical alterations in CMS brains.

Epilepsy

Monday 1 June 2015

Jie Zheng¹, Rushi Rajyaguru¹, Jeffery Riley¹, Gultekin Gulsen¹, Bruce Hermann², and Jack Lin^1
1University of California, Irvine, Irvine, California, United States, ²University of Wisconsin School of Medicine and Public Health, Wisconsin, United States

Our structural brain network will change topologically with time. Our study focuses on revealing the difference between growing teenagers from healthy group and epilepsy group during brain network shaping procedure. A control study has been set up over the first two years after epilepsy onset among children with localization related epilepsy (LRE) group and idiopathic generalized epilepsy (IGE) group. Then we introduced graph theory method to demonstrate the difference of global graphical properties alternation among three groups. Based on our results, the new-onset pediatric epilepsy leads to abnormal neurodevelopment structural trajectories with less network efficiency and less optimal small world configuration.

Eun Kyoung Lee¹ and Eun Ja Lee^1
1Radiology, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Korea

Nonketotic hyperglycemia (NKH) have been reported to induce seizures, and may cause transient signal changes on MRI. The aim of our study was to describe the characteristic MRI abnormalities in patients with NKH complicated with seizures and to evaluate the diagnostic value of CE-FLAIR. We retrospectively studied MRI abnormalities in 10 patients with seizures associated with NKH. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2WI/FLAIR imaging in all patients with overlying cortical hyperintensities in 2 patients. Focal overlying cortical or leptomeningeal enhancement on CE-T1WI or CE-FLAIR was observed in all patients. CE-FLAIR was superior to CE-T1WI for detecting characteristic leptomeningeal enhancement. Although these MRI abnormalities pose a broad differential diagnosis, recognition of these radiologic abnormalities in NKH is important in restricting unwarranted investigations and to institute early therapy.

Megan L. McGill¹, Orrin Devinsky², Xiuyuan Wang², Brian T. Quinn², Heath Pardoe², Chad Carlson², Tracy Butler², Ruben Kuzniecky², and Thomas Thesen^2
1Radiology, New York University School of Medicine, New York, NY, United States, ²Comprehensive Epilepsy Center, Neurology, New York University School of Medicine, New York, NY, United States

This study employs functional and anatomic analysis of MRI scans to detect focal and network abnormalities in Idiopathic Generalized Epilepsy (IGE), a diffuse neurologic disorder characterized by normal appearing clinical MRI scans. Analysis of resting state functional MRI, diffusion tensor imaging, and quantitative morphometric analysis shows that focal functional differences can be detected in the thalamo-prefrontal network, though no morphometric differences were detected between IGE subjects and normal controls. Our results both point to underlying functional abnormalities in IGE and highlight the power of MRI to better characterize neurological disease.

Xiaoqin GUO^1,2, Shangchen XU³, Guangbin WANG¹, Yi ZHANG⁴, Lingfei GUO¹, and Bin ZHAO^1
1MRI, Shandong Medical Imaging Research Institution, Jinan, Shandong, China, ²Medicine, Shandong University, Jinan, Shandong, China, ³Neurosurgery, Shandong Provincial Hospital, Shandong, China, ⁴Medical Imaging Processing Center, Shandong Medical Imaging Research Institution, Shandong, China

Structural MRI contributes a lot in the lateralization of temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS), especially FLAIR sequence. However, 1/3 TLE patients appear normal on structural MRI. MRI perfusion and DWI have been reported helpful for lateralization of non-MTS TLE patients. Our study aims to explore their performance of lateralization in TLE using ASL and DWI techniques by calculating asymmetry indices of regional cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values. The sensitivity/specificity of lateralization in TLE is 55.6%/100% by only FLAIR images, and can reach to 85.2%/100% and 70.4% /100% by adding asymmetry indices of CBF and ADC values as covariates for ROC curves respectively. We concluded that ASL and DWI can help for lateralization in TLE and ASL is better.

Yao-Chia Shih^1,2, Yu-Jen Chen², Yung-Chin Hsu², Yu-Chun Lo², Hong-Huei Liu³, and Wen-Yih Issac Tseng^2,4
1Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taipei, Taiwan, ²Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taipei, Taiwan, ³Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taipei, Taiwan,⁴Molecular Imaging Center, National Taiwan University, Taipei, Taipei, Taiwan

Unilateral mesial temporal lobe epilepsy (MTLE) with HS was regarded as a network disorder. In the present study, we proposed a surface-based analysis and a tract-specific analysis over the whole brain to detect, respectively, the GM and WM alterations in unilateral MTLE with HS. Since the sclerotic hippocampus may generate epileptic activities and spread via the WM tracts to other extratemporal regions, we hypothesized that the WM alterations due to MTLE with HS might affect the averaged cortical thickness of the connected GM regions. In addition, we assumed that left and right MTLE with HS should exhibit different epileptic networks. Using the surfaced-based analysis and TBAA method to assess, respectively, the WM and GM alterations over the whole brain, this work demonstrated different epileptic brain networks between left and right MTLE with HS.

Clarissa Gillmann¹, Roland Coras², Michael Uder¹, Ingmar Blümcke², and Tobias Bäuerle^1
1Institute of Radiology, University Hospital Erlangen, Erlangen, Germany, ²Institute of Neuropathology, University Hospital Erlangen, Erlangen, Germany

Purpose of this study was to investigate whether sclerotic and non-sclerotic hippocampal subfields can be discriminated by high-resolution, multiparametric MR-microscopy at 7T ex vivo. T1-, T2- and T2*-relaxation times, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were determined in hippocampal subfields CA1-CA4 for both, a resected non-sclerotic and a resected sclerotic hippocampus. On morphologic images, distinct differences in the pyramid cell layer between both hippocampi are clearly visible. With respect to multiparametric imaging, ADC is most promising for differentiation of sclerotic and non-sclerotic subfields.

Kouhei Kamiya¹, Yuichi Suzuki², Shiori Amemiya¹, Naoto Kunii³, Kensuke Kawai⁴, Harushi Mori¹, Akira Kunimatsu¹, Nobuhito Saito³, Shigeki Aoki⁵, and Kuni Ohtomo^1
1Department of Radiology, The University of Tokyo, Bunkyo, Tokyo, Japan, ²Department of Radiological Technology, The University of Tokyo Hospital, Bunkyo, Tokyo, Japan, ³Department of Neurosurgery, The University of Tokyo, Bunkyo, Tokyo, Japan, ⁴Department of Neurosurgery, NTT Medical Center Tokyo, Shinagawa, Tokyo, Japan,⁵Department of Radiology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan

This study aimed to investigate the utility of machine learning approach with DTI structural connectome for lateralization of epileptogenicity in TLE. DTI (b=0, 1000 s/mm2; 13 MPGs; 3mm iso-voxel) and 3D-T1WI were obtained in 41 patients with TLE (right/left 13/28). For each patient, an 83x83 connectome matrix was generated and graph theoretic regional network measures (degree, clustering coefficient, local efficiency, and betweeness centrality) were calculated. The regional measures were used to train the classifier using the sparse linear regression and support vector machine (SVM). SVM demonstrated excellent discrimination between left and right TLE, with 92.7% accuracy in leave-one-out cross validation.

Mojdeh Zamyadi¹, Carter Snead¹, Sam Doesburg¹, Mary Lou Smith¹, and Elysa Widjaja^2
1Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada, ²Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada

The aims of this study were to investigate the structural whole brain networks using graph theoretical measures in children with localization-related epilepsy, including subgroups with frontal and temporal lobe epilepsy relative to healthy controls. We also assessed the relation between graph measures of structural connectivity with and intelligence quotient (IQ) as well as other clinical parameters. We found disruption in global and regional networks, and reduced connectivity between multiple lobes in children with localization-related epilepsy. No associations was found between global network properties, IQ and clinical parameters.

Niels Leonard Schwaderlapp¹, Philipp Janz², Jochen Leupold¹, Ute Häussler², Thomas Lange¹, Dominik v. Elverfeldt¹, Carola Haas², Jürgen Hennig¹, Laura-Adela Harsan¹, and Pierre LeVan^1
1Medical Physics, University Medical Center Freiburg, Freiburg, BW, Germany, ²Exp. Epilepsy Research, University Medical Center Freiburg, Freiburg, BW, Germany

Epileptogenesis involves metabolic and micro structural alterations within subfields of the brain. Non-invasive in-vivo monitoring of these processes provide deeper insights and might reveal MR biomarkers for epilepsy. In this longitudinal study, we employed 1H MR spectroscopy and high-resolution diffusion imaging in combination with tractography to monitor the developments during epileptogenesis in a mouse model of temporal lobe epilepsy. We identified early changes of relevant metabolites (GABA, Glu, Lac, NAA, Ins) and tracked the progression of structural changes (gliosis) in hippocampal subfields which were validated by subsequent in-vivo EEG recordings and immunohistochemistry.

Yijen Lin Wu^1,2, Patrice Pearce¹, Amedeo Rapuano³, T. Kevin Hitchens⁴, Nihal deLanerolle³, and Jullie W Pan^1,5
1Neurology, University of Pittsburgh, Pittsburgh, PA, United States, ²Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States, ³Neurosurgery, Yale University, New Haven, CT, United States, ⁴Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, ⁵Radiology, University of Pittsburgh, Pittsburgh, PA, United States

The development of spontaneous recurrent seizures (epilepsy) is a complex process that commonly ensues after an initial cerebral insult. We used MR spectroscopy and T2 relaxometry in a rodent model to understand how moderate variability in status epilepticus influences such metabolic injury in early epileptogenesis. The nature of the injury can be considered to be classified as neuronal, glial or joint pathophysiological processes. The MR spectroscopic and imaging can be informative towards individual identification of injury severity and may enable identification of a MR based biomarker to predict the development of epilepsy.

Marisa Blitstein¹, Sandra Rincon¹, Paul Caruso¹, Ronald Thibert², Ramon Gilberto Gonzalez^1,3, and Eva-Maria Ratai^1,3
1Department of Radiology, Neuroradiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ²Neurology / Pediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ³A. A. Martinos Center for Biomedical Imaging, MA, United States

The purpose of our study was to retrospectively evaluate MRI, MRS, and clinical data to determine how often MRS added information to conventional MRI for evaluation of seizure in pediatric patients. A database search between 1/1/2011 and 12/31/2013 to identify patients <18 years old with both MRI and MRS for evaluation of seizure resulted in 241 cases. In our series, MRS yielded additional information for 40% (96/241) of all patients. The largest subsets of patients that had MRS exams yielding additional information were patients with hypoxic ischemic injury, distinguishing dysplasia from neoplasm, and prompting metabolic or genetics workup.

Helen Wu^1,2, Danielle Senador³, Matthew Galloway⁴, Jeffrey Loeb⁵, and Jeffrey Stanley^4
1Wayne State University School of Medicine, Detroit, MI, United States, ²MD/PhD Program, Wayne State University School of Medicine, Detroit, MI, United States, ³Wayne State University School of Medicine, MI, United States, ⁴Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, MI, United States,⁵Neurology and Rehabilitation Medicine, University of Illinois at Chicago, IL, United States

We used a chronic tetanus toxin rat model of interictal spiking as a platform to investigate longitudinal metabolite changes associated with epileptogensis. Our 1H MRS performed in vivo at 7T provides the opportunity to examine neocortical metabolite changes associated with the epileptogenic process in context of concurrent long term EEG changes. The goal of this study is to identify key noninvasive biomarkers associated with epileptogensis in the neocortex and characterize the potential interplays between metabolite and electrophysiologic changes during epilepsy development.

Stefania Evangelisti¹, Laura Ludovica Gramegna¹, Claudia Testa¹, David Neil Manners¹, Stefano Zanigni¹, Claudio Bianchini¹, Francesca Bisulli^2,3, Laura Licchetta², Ilaria Naldi², Lorenzo Ferri², Paolo Tinuper^2,3, Caterina Tonon¹, and Raffaele Lodi^1
1Functional MR Unit, Policlinico S.Orsola-Malpighi, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy, ²Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy, ³IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy

Nocturnal frontal lobe epilepsy (NFLE) is a heterogeneous disorder characterized by sleep-related motor events of various semiology, intensity and duration. The pathophysiology of the seizures has not yet been completely elucidated. This study evaluated fMRI resting state functional connectivity in NFLE patients compared to controls. NFLE patients showed greater functional connectivity between precuneus, superior parietal lobe, primary and supplementary motor areas, and thalamus. The thalamus is a structure involved in non-REM spindles and the generation of k-complexes. Our results may suggest an alteration of the arousal regulatory system, with a particular excitability of the cortex during non-REM sleep.

Jianzhong Yin^1,2, Bofeng Zhao¹, Zhijuan Chen³, Weidong Yang³, Yu Qing⁴, Li Cai⁵, Panli Zuo⁶, Hongyan Ni^1,2, and Wen Shen^1,2
1Radiology Department, Tianjin First Central Hospital, Tianjin, Tianjin, China, ²Tianjin Medical Imaging Institution, Tianjin, China, ³Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China, ⁴Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China, ⁵Clinical PET-CT Center, Tianjin Medical University General Hospital, Tianjin, China, ⁶MR Collaboration, Siemens Healthcare China, Beijing, China

We made systematic comparison of the findings of resting state fMRI with other localization techniques, including VEEG, PET, and MRI, for epileptogenic zone. It revealed that RS-MRI based on those analysis methods has almost the same sensitivity of PET, and almost the same specificity of VEEG for localization of epileptogenic zone. Although there are still some way off for routine usage, our findings suggest that RS-fMRI, which has the advantages of non-invasiveness, fairly high spatial resolution and easy implementation, could be a powerful and efficient tool for further clinical application.

Multiple Sclerosis

Monday 1 June 2015

Sneha Pandya¹, Elizabeth Monohan², Michael Dayan¹, Susan A. Gauthier², and Ashish Raj^1
1Radiology, Weill Cornell Medical College, New York, NY, United States, ²Neurolgy, Weill Cornell Medical College, New York, NY, United States

Myelin water fraction (MWF) can be measured using multi-echo MR T2 relaxometry. MWF was shown to correspond closely with the integrity of myelin in white matter tissue, and is a sensitive marker of demyelination. However, whole brain MWF quantification in a routine clinical setting does not account for acute events accompanied by new lesions, including inflammation and edemation, and is therefore rather sensitive to those effects in addition to measuring myelin loss.We have developed a sensitive measure of these effects by computing the first and second moments of the intra/extra-cellular T2 distribution obtained from the fitted T2 spectrum.

Elisabetta Pagani¹, Maria A. Rocca^1,2, Paolo Preziosa^1,2, Sarlota Mesaros³, Massimiliano Copetti⁴, Melissa Petrolini¹, Jelena Drulovic³, and Massimo Filippi^1,2
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ³Neurology Clinic, Clinical Centre of Serbia, University of Belgrade, Belgrade, Yugoslavia, ⁴Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

The identification of imaging biomarkers for monitoring disease progression in multiple sclerosis is an unmet need. In this study, we assessed the value of conventional and quantitative MRI measures of brain and spinal cord in predicting disability and cognitive worsening in multiple sclerosis patients after 5 years. A random forest analysis was performed to identify predictors of neurologic deterioration, phenotype modification and cognitive worsening at followup. The results showed that, while disability deterioration seems mainly due to disruption of white matter integrity, cognitive dysfunction is the result of a complex interplay between white matter and grey matter damage.

Refaat E Gabr¹, Xiaojun Sun¹, Amol S Pednekar², and Ponnada A Narayana^1
1Department of Diagnostic and Interventional Imaging, The University of Texas Health Science Center at Houston, Houston, TX, United States, ²Philips Healthcare, Cleveland, OK, United States

Optimization of double inversion recovery protocols is usually performed based on the expected relaxation times in a certain class of patients. Natural and disease-related variations in tissue relaxation cause inconsistent tissue suppression and suboptimal contrast across studies. In this work we explore a patient-specific approach for maximizing tissue contrast based on fast relaxation scout and pseudo-real-time image processing pipeline integrated into a clinical scanner. Experiments in healthy subjects show that subject-specific optimizations produce large gains in tissue contrast without scan time penalty, with only one minute of processing time.

Govind Nair¹, Danish Ghazali¹, Blake Snyder¹, Joan Ohayon¹, Daniel S Reich¹, Irene Cortese¹, and Bibiana Bielekova^1
1NINDS, National Institutes of Health, Bethesda, MD, United States

Quantitative MRI (qMRI) markers of disease progression such as tissue volume, DTI, and quantitative T1 (qT1) from the brain and cervical spinal cord were assessed for their sensitivity to disease progression in primary progressive multiple sclerosis (PPMS). Thirty-one PPMS patients were assessed twice longitudinally using qMRI and clinical scores. Among the qMRI parameters that showed change at 1 year were qT1 from the upper cervical spinal cord, thalamic and ventricular volumes, FA from the corpus callosum, and MD from caudate. A majority of the qMRI from brain did not show any changes, probably reflecting the pathophysiology of PPMS.

Thanh D Nguyen¹, Kofi Deh¹, Sneha Pandya¹, Elizabeth Monohan¹, Ashish Raj¹, Yi Wang¹, and Susan A Gauthier^1
1Weill Cornell Medical College, New York, NY, United States

The objective was to develop fast and reproducible whole brain myelin water mapping for longitudinal study of multiple sclerosis. A 4 min Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) sequence together with a robust multi-voxel Spatially constrained Nonlinear (SPAN) data fitting algorithm enabled highly reproducible myelin water fraction measurements between repeated scans (negligible bias with 2% limits of agreement on a per voxel basis).

Barbara Basile^1,2, Laura Serra¹, Barbara Spanò³, Valeria Studer⁴, Silvia Rossi⁴, Diego Centonze⁴, Carlo Caltagirone⁵, and Marco Bozzali^1
1Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, ²Association of Cognitive Psychotherapy, School of Cognitive Psychotherapy, Roma, Italy, ³Neuroimaging Laboratory, Santa Lucia Foundation, Roma, Italy, ⁴Department of Neuroscience, University of Rome ‘Tor Vergata’, Rome, Italy, ⁵Institute of Neurology, Università Cattolica, roma, Italy

"Cognitive Reserve" (CR) postulates the existence of functional brain mechanisms that are able to cope with cerebral damage. Cognitive functioning is impaired in multiple sclerosis (MS), but some patients are able to withstand considerable disease burden, without cognitive impairment. The aim of this study was to investigate the association between functional connectivity (FC), measured with Resting-state-(RS)fMRI method, and levels of CR, in patients with MS. Correlation analyses between levels of CR and those RS-networks that are likely to be affected in MS (i.e., Sensory-Motor and Default-Mode) revealed specific significant associations, suggesting the relevance of CR in modulating impairment in MS.

AmirHussein Abdolalizadeh^1,2, Arash Nazeri², Tina Roostaei², Mohammad Ali Sahraian², Shokufeh Sadaghiani², Bahram Mohajer¹, and Mohammad Hadi Aarabi^1
1Interdisciplinary Neuroscience Research Program (INRP), Tehran, Tehran, Iran, ²Multiple Sclerosis Research Center (MSRC), Tehran, Iran

Multiple Sclerosis (MS) is an autoimmune disease causing neuronal injury. Diffusion Weighted Imaging have been used to investigate different aspects of MS, and structural connectivity studies have shown alterations in brain connectivity parameters of MS patients. We used Network Based Statistics to investigate changes in white matter structural networks of Relapsing Remitting MS patients using diffusion tensor imaging and graph theories. It has been shown that, compared to healthy controls, MS patients have significantly lower linear anisotropy, number of tracts, average tract length and tract volume. Supplementary Motor Areas (Right and Left) and Right Precuneus were the main regions involved.

Lesley M Foley¹, Shinjini Kundu², Wendy Fellows-Mayle³, T Kevin Hitchens^1,4, Gustavo K Rohde², Ramesh Grandhi³, Christopher M Bonfield³, and Mark P Mooney^5
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, ²Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States, ³Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States, ⁵Department of Anthropology, University of Pittsburgh, Pittsburgh, PA, United States

Craniosynostosis is where one or more of the calvarial sutures fuse prematurely. This work examines microstructural integrity of white matter, using DTI. Rabbits were assigned to one of nine groups, wild type (WT), complete fusion of the coronal suture (BC), and surgically corrected (BC-SU) at 12, 25 or 42 days. As age increased neurophysiological differences between WT, BC, and BC-SU groups become more pronounced, especially in the corpus callosum, cingulum and fimbriae. Using a linear support vector machine classifier, classification into WT, BC, and BC-SU groups was possible with high accuracy. DTI revealed differences between craniosynostotic and surgically corrected animals.

Louise Pape¹, Artem Mikheev¹, Jeffrey Huang¹, Joseph Herbert¹, Henry Rusinek¹, and Yulin Ge^1
1Radiology/Center for Biomedical Imaging, NYU Langone Medical Center, New York, NY, United States

Cortical atrophy is a key imaging hallmark of multiple sclerosis (MS). The aim of this study was to investigate the differences in sulcal volume, width and depth of the central sulcus as well as pericentral cortical gray matter (Pc-CGM) thickness between MS patients and healthy controls. Results showed increased volume and width of the central sulcus and decreased Pc-CGM in patients. The sulcal changes correlated with the local atrophy measure of Pc-CGM in patients. Since CS metrics are correlated with clinical disability measure, there is potential to use them as quantitative markers of progression.

Mark J. Lowe¹, Katherine A. Koenig¹, Xiaopeng Zhou¹, Wanyong Shin¹, Robert Bermel², Lael Stone², and Micheal D. Phillips^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Neurologic Institute, Cleveland Clinic, Cleveland, OH, United States

It is known that multiple sclerosis results in decreased cerebral metabolic rate of oxygen and blood flow. Both of these are critical elements in cerebrovascular reactivity to neuronal activation. It has been shown that resting state fluctuation amplitude (RSFA) can be a surrogate to hypercapnic challenge as a measure of cerebrovascular reactivity. We show that the correlation between BOLD activation and RSFA is much weaker in MS patients than in healthy controls, indicating that cerebrovascular reactivity may be compromised in MS populations.

Alberto De Luca^1,2, Marco Castellaro¹, Stefania Montemezzi³, Massimiliano Calabrese⁴, and Alessandra Bertoldo^1
1Department of Information Engineering, University of Padova, Padova, PD, Italy, ²Department of Neuroimaging, Scientific Institute, IRCCS "Eugenio Medea", Bosisio Parini, LC, Italy, ³Radiology Unit, Azienda Ospedaliera di Verona, Verona, Italy, ⁴Neurology Section, Department Of Neurological and Movement Sciences, University Hospital of Verona, Verona, Italy

Multiple Sclerosis (MS) population presents higher prevalence of temporal lobe epilepsy than the healthy population. In this work we investigate if the combination of a multi-shell diffusion weighted acquisition with the NODDI model can provide insights of the differences between the hippocampi of epileptic and non-epileptic subjects in a MS population. Results show that while the fractional anisotropy index is not statistically different, the NODDI derived quantities ODI and Kappa reveal statistical differences in both the left and right hippocampi, that appear to link epileptic episodes with alterations of the fibers in these areas.

Courtney A Bishop^1,2, Emma McCarthy³, Richard Nicholas², Lesley Honeyfield⁴, Paolo A Muraro^2,5, Adam D Waldman^2,4, and Rexford D Newbould^1,6
1Imanova Centre for Imaging Sciences, London, United Kingdom, ²Division of Brain Sciences, Imperial College London, London, United Kingdom, ³University of Warwick, Coventry, United Kingdom, ⁴Department of Imaging, Imperial College Healthcare NHS Trust, United Kingdom, ⁵Department of Clinical Neurosciences, Imperial College Healthcare NHS Trust, United Kingdom, ⁶Division of Experimental Medicine, Imperial College London, United Kingdom

T1-weighted volumes covering the entire cervical cord were acquired on 162 RRMS patients with an average EDSS of 3.5 and average disease duration of 4.4 years, but separated as two age groups (mean difference of 13.8 years). Semi-automated delineation of the spinal cord along the C2-C5 region revealed mean cross-sectional area (CSA) measures were significantly smaller in the older MS patients compared to the young (P=0.007) after accounting for clinical covariates, and correlated moderately well with disability (R=-0.37-0.38).

Blessy Mathew¹, Mark J. Lowe¹, and Rob Bermel^1
1Cleveland Clinic, Cleveland, OH, United States

ON affects almost 50% of MS patients. It involves inflammatory demyelination of the optic nerve leading to partial or complete loss of vision. Recovery from ON is variable, and a minimum of six months were required to have passed after onset of unilateral ON for recovery to have reached a plateau. In our study we explored the application of fcMRI in MS patients with ON, between LGN and V1 correlation to visual acuity. We show that visual acuity is related to LGN-V1 functional connectivity using fcMRI. This relationship appears to be reduced or non-existent when visual acuity is very poor.

Guillaume Bonnier^1,2, Bénédicte Mortamet^1,2, Jean-Philippe Thiran², Gunnar Krueger^1,2, Tobias Kober^1,2, and Cristina Granziera^1
1Siemens ACIT – CHUV Radiology, Siemens Healthcare IM BM PI & Department of Radiology CHUV, Lausanne, Vaud, Switzerland, ²LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

Conventional magnetic resonance imaging of patients with multiple sclerosis provides only limited insights into the nature of brain tissue damage with modest clinical-radiological correlations. In this study, we evaluated the 2 years longitudinal evolution of conventional and non-conventional markers of MS disease, in a cohort of patients with relapsing-remitting multiple sclerosis. Our cohort of patients did not show any longitudinal evolution of microstructural properties in brain normal-appearing tissue and no correlation was found between individual plaques changes and microstructural properties of brain. Our study provides evidence of the complementary nature of conventional and unconventional MRI measures for proper MS patients follow-up.

Jan-Mendelt Tillema¹, John Port², Pascal Atanga¹, Yunhong Shu^2,3, Claudia Lucchinetti¹, and Istvan Pirko^1
1Neurology, Mayo Clinic, Rochester, MN, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States, ³Biomedical Engineering and Medical Physics, Mayo Clinic, Rochester, MN, United States

In this study, a novel double inversion recovery pulse sequence was applied in patients with Multiple Sclerosis, suppressing signal from CSF and gray matter. We show a new ring pattern of signal change surrounding WM lesions that is not seen on standard DIR. Approximately 50% of the identified lesions reveal this rim pattern of hypo-intense signal change, most prominent in larger and periventricular lesions.

Lijie Tu^1,2, Cynthia Wisnieff³, Susan Gauthier⁴, David Pitt⁵, Yi Wang¹, and Tian Liu^6
1Radiology, Weill Cornell Medical College, New York, NY, United States, ²Applied & Engineering Physics, Cornell University, Ithaca, NY, United States, ³Tufts University, MA, United States, ⁴Weill Cornell Medical College, New York, NY, United States, ⁵Neurology, Yale University, New Haven, CT, United States, ⁶Medimagemetric, LLC, New York, NY, United States

To image multiple sclerosis lesions in white matter, a tensor model may be needed to account for the anisotropic susceptibility effect. In this study, we applied a vector model for quantitative susceptibility mapping in human brain, which only requires a single scan. Comparison with histology confirmed that this method is able to detect spatial changes of susceptibility anisotropy. In vivo results suggest that the susceptibility observed in multiple sclerosis lesions arise primarily from iron instead of demyelination.

Rebecca Sara Samson¹, Manuel Jorge Cardoso^2,3, Nils Muhlert¹, Varun Sethi¹, Oezguer Yaldizli¹, Maria A Ron¹, Sebastian Ourselin^2,3, David H Miller¹, Claudia A M Wheeler-Kingshott¹, and Declan T Chard^1,4
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Centre for Medical Image Computing, UCL Department of Computer Sciences, London, England, United Kingdom, ³Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, England, United Kingdom, ⁴NIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom

Outer cortical magnetization transfer ratio (MTR) has the potential to be a sensitive measure of pathology linked to clinical disease progression in relapse-onset multiple sclerosis (MS). We investigated whether inner and outer cortical grey matter (GM) magnetization transfer ratio (MTR) changes are associated with MR-visible lesions, normal-appearing GM (NAGM) abnormalities, or both, in MS patients, by examining the co-localisation of cortical lesions marked on phase sensitive inversion recovery images with inner and outer cortical bands. Our findings indicate that reductions in outer cortical MTR are mostly due to changes beyond MR-visible lesions.

Xiaozhen Li^1,2, Peter van Gelderen¹, Pascal Sati³, Jacco de Zwart¹, Daniel Reich³, and Jeff Duyn^1
1Advanced MRI Section, LFMI, NINDS, National Institutes of Health, Bethesda, Maryland, United States, ²Dept. NVS, Karolinska Institutet, Huddinge, Stockholm, Sweden,³Translational Neuroradiology Unit, DNN, NINDS, National Institutes of Health, Bethesda, Maryland, United States

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by the formation of focal demyelinated (‘plaques’, or ‘lesions’). To detect this ongoing demyelination in MS patient brains in newly forming (Gadolinium-enhancing) lesions, we studied changes in T2* relaxation over serial scans covering a 6-month time span. Use of a three-component model-fit to the data allowed us to monitor changes in myelin water (and thus indirectly myelin content), axonal water and interstitial water. Our results showed the changes for R2* (1/T2*) of axonal water at different lesion evolution stages, which may help further understand the disease evolution in MS.

Victoria M Leavitt¹, Alayar Kangarlu², Feng Liu², Claire S Riley³, and James F Sumowski^4
1Columbia University Medical Center, New York, New York, United States, ²New York State Psychiatric Institute, New York, New York, United States, ³Columbia University Medical Center, New York, United States, ⁴Kessler Foundation, New Jersey, United States

We hypothesize that elevated body and brain temperature in patients with relapsing-remitting multiple sclerosis (RRMS) indicates clinically-silent disease activity, i.e., inflammatory processes. MRS thermometry was used to measure brain temperature in RRMS and progressive-type MS patients. Brain temperature was elevated in RRMS patients relative to progressive-type patients. Monitoring brain and body temperature may allow us to detect clinically-silent inflammatory processes in patients with RRMS.

Mara Cercignani¹, Giovanni Giulietti², Barbara Spano'², and Marco Bozzali^2
1CISC, Brighton and Sussex Medical School, Brighton, East Sussex, United Kingdom, ²Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy

The g-ratio is a reliable index of axonal myelination, and can be related to the physiology and function of an axon. Here we combine diffusion and magnetization transfer to map the MS lesion g-ratio and relate it to variable pathological substrates.

Bing Yao^1,2, Sarah Wood^1,3, Zhiguo Jiang⁴, Glenn Wylie^1,2, and John DeLuca^1,2
1Rocco Ortenzio Neuroimaging Center, Kessler Foundation, West Orange, NJ, United States, ²Department of Physical Medicine & Rehabilitation, Rutgers University, Newark, NJ, United States, ³Psychology Department, Montclair State University, Montclair, NJ, United States, ⁴Human Performance Engineering Lab, Kessler Foundation, West Orange, NJ, United States

Hypointensity of deep brain gray matter structures in T2*-weighted images (T2WI) of multiple sclerosis (MS) patients has been reported and suggested to represent increased iron deposition. However, these findings are difficult to generalize as the contrast in T2WI depends on several MR parameters including TE, TR, and others. Here, we explored using quantitative susceptibility contrast imaging including R2* and quantitative susceptibility map to identify characteristic regions suggestive of increased iron deposition in MS patients.

Sourajit Mitra Mustafi¹, Chandana Kodiweera², Jennifer S Randolph³, James C Ford³, Heather A Wishart³, and Yu-chien Wu^1
1Center for Neuroimaging, Indiana Univeristy, Indianapolis, Indiana, United States, ²Dartmouth College, NH, United States, ³Dartmouth Medical School, Lebanon, NH, United States

Conventional MR imaging, including T1-weighted (pre-/post- contrast), T2-weighted, and T2-weighted fluid-attenuated inversion recovery scans, are used in the diagnosis and monitoring of MS but leave the underlying micromechanisms of tissue damage unclear. Diffusion MRI measures water diffusion behaviors in biological systems, and is sensitive to microstructural white matter (WM) changes in MS. In this study, we used neurite orientation dispersion and density imaging (NODDI) to study the brain in humans with MS. NODDI hypothesizes WM microstructures in three compartments: extracellular, intracellular and cerebrospinal fluid compartment. NODDI information may help explain the microstructural changes in MS at cellular level.

Thomas Martin Doring¹, Vanessa Granado², Gustavo Tukamoto³, Fernanda Rueda³, Andreas Deistung⁴, Juergen Reichenbach⁵, Emerson Gasparetto⁶, and Ferdinand Schweser^7
1Radiodiagnostic Imaging, DASA, Rio de janeiro, Rio de Janeiro, Brazil, ²Radiologia, CDPI, Rio de Janeiro, Brazil, ³CDPI, Rio de Janeiro, Brazil, ⁴Medical Physics, Uni Jena, Thueringen, Germany, ⁵Medical Physics Group, Uni Jena, Thueringen, Germany, ⁶DASA, Rio de Janeiro, Brazil, ⁷CTRC and Buffalo Neuroimaging Analysis Center, University of NY, Buffalo NY, United States

Neuromyelitis optica (NMO) is a severe, inflammatory demyelinating disease that typically affects optic nerve and spinal cord. The purpose of the current study was to investigate brain iron and myelin in NMO patients using two quantitative imaging techniques, R2* mapping and the relatively new Quantitative Susceptibility Mapping. Advanced neuroimaging techniques have recently been explored to discover new diagnostic criteria to detect NMO and to overcome the problem to distinguish this disease from MS.

Patricia Alves Da Mota¹, Ferran Prados², Wallace J Brownlee¹, Manuel Jorge Cardoso², Matteo Pardini¹, Nicolas Toussaint², Declan T Chard¹, Sébastien Ourselin², David H Miller¹, and Claudia AM Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Department of Medical Physics and Bioengineering Wolfson House, Translational Imaging Group CMIC, London, England, United Kingdom

Brain atrophy is a well established pathologically feature of multiple sclerosis (MS). Here we compare GIF, a novel segmentation technique which has not been previously applied in people with MS, to SPM12 results. Acknowledging the small number of subjects, statistical measures and qualitative assessment showed that GIF provides a relatively significant improvement in segmentation accuracy when compared to SPM12, with an improved agreement between observers (r=0.740 VS r=0.203). GIF was also found to be more robust (i.e. lower standard deviations) at estimating brain atrophy (i.e. volume fractions) on both HC and MS subjects.

Steven R Kecskemeti¹, Andrew L Alexander^1,2, and Aaron S Field^3
1Waisman Center, University of Wisconsin, Madison, Wisconsin, United States, ²Medical Physics, University of Wisconsin, Madison, Wisconsin, United States, ³Radioilogy, University of Wisconsin, Madison, Wisconsin, United States

This study presents a longitudinal study of 8 monthly scans using 3D MPnRAGE of two volunteers with multiple sclerosis. T1 maps of normal appearing white matter and gray matter are highly reproducible as determined by the temporal coefficient of variation. Coefficient of variation for a WM lesion that appeared during the study was approximately 8x larger than normal appearing WM, suggesting coefficient of variation of T1 across time may be a useful biomarker to describe progression or treatment of MS.

Nathan C Wetter^1,2, Elizabeth A Hubbard³, Robert W Motl³, and Bradley P Sutton^1,2
1Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, IL, United States, ³Kinesiology and Community Health, University of Illinois at Urbana-Champaign, IL, United States

T2 white matter hyperintensities are a defining clinical feature of Multiple Sclerosis (MS), and T2 Lesion Volumes (T2LV) have been an important biomarker in MS research. Numerous methods have been proposed for T2LV quantification, but they usually require human intervention and multiple images, and are not easily accessible. We propose, to the best of our knowledge, the first fully-automated, single-image T2LV quantification method. It is based upon the widely popular open-source imaging toolkit FSL, combining its components in an intuitive way to produce reliable, consistent lesion volumes and masks.

Traumatic Brain Injury

Monday 1 June 2015

David K Wright^1,2, Chris Van Der Poel³, Li Yang⁴, Stuart McDonald³, Roger Ordidge¹, Terence J O'Brien⁴, Leigh A Johnston⁵, and Sandy R Shultz^4
1Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia, ²The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia, ³Department of Human Biosciences, La Trobe University, Victoria, Australia, ⁴Department of Medicine, The University of Melbourne, Victoria, Australia, ⁵NeuroEngineering Laboratory, School of Engineering, The University of Melbourne, Victoria, Australia

Traumatic brain injury (TBI) has been controversially proposed as a risk factor for the later onset of amyotrophic lateral sclerosis (ALS). Here we studied the potential relationship between TBI and ALS in an experimental model of TBI using MRI, pathology and behavioural analyses. TBI rats had significant motor cortex atrophy, corticospinal tract degeneration, increased expression of TDP-43, motor neuron loss, increased expression of m-calpain and atrogin-1, muscle atrophy and behavioural impairments. Taken together, these findings resemble the pathological and functional abnormalities common in ALS, and support the notion that TBI can induce a progressive ALS-like disease process.

Qiang Shen¹, Lora Talley Watts¹, Shiliang Huang¹, Michael O'Boyle¹, Justin Alexander Long¹, and Timothy Q Duong^1
1Research Imaging Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Although traumatic brain injury has been investigated using variable imaging techniques, including MRI, the relatively low spatial resolution has limited the ability to determine tissue injury type and to predict the tissue fate. Results previously reported are controversial, and are seemingly dependent on the severity of injury. Furthermore, prediction of tissue fate in TBI using low resolution data is very difficult. This study employed high spatial resolution MRI to investigate moderate TBI longitudinally up to one month post injury. This study provides a better delineation of tissue injury types and assists in the prediction of tissue fate following TBI.

Chandler Sours^1,2, Elijah George^1,2, Steven Roys^1,2, Jiachen Zhuo^1,2, and Rao P Gullapalli^1,2
1Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ²Magnetic Resonance Research Center, Baltimore, MD, United States

The aim of this study is to investigate the acute functional alterations in the thalamus following mild traumatic brain injury (mTBI) using resting state fMRI (rs-fMRI) and magnetic resonance spectroscopy imaging (MRSI). Results suggest that in addition to reduced NAA/Cr in the thalamus, acute mTBI patients have increased thalamo-cortical connectivity, including both cortical areas associated with primary sensory processing and cortical areas associated with the Default Mode Network. These results provide evidence for a functionally damaged thalamus in the initial days following mTBI and may be associated with common post concussive symptoms experienced by these patients.

Sanjay Verma¹, Bhanu Prakash KN¹, Sankar Seramani¹, Enci Mary Kan², Kian Chye Ng², Mui Hong Tan², Jia Lu², and S Sendhil Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore

Traumatic brain injury (TBI) is a serious and global public health issue. Focal and diffuse are the two ways to classify brain injuries. Multi-echo Susceptibility weighted imaging provides phase with better SNR and CNR and R2*, making it a sensitive technique for brain injury. A comparative study of focal (fluid percussion injury) and diffuse (open field blast) TBI using multi echo SWI has been made in this study.

Armin Iraji¹, Natalie Wiseman¹, Robert Welch¹, Brian O'Neil¹, Andrew Kulek¹, Syed Imran Ayaz¹, E Mark Haacke¹, and Zhifeng Kou^1
1Wayne State University, Detroit, Michigan, United States

Mild traumatic brain injury (mTBI) is a significant public healthcare burden that costs the nation billions of dollars each year. Most mTBI patients have normal findings in clinical neuroimaging; however, there are several cognitive and emotional symptoms that can impact patients’ quality of life. Therefore, we expected to see changes in brain regions associated with higher order functions. The thalamus and anterior cingulate cortex (ACC) are the two main centers of information processing, cognitive and affective functions, and regulation in the brain, and are structurally and functionally connected to each other. Thus, the connections between these regions was investigated longitudinally.

Shiyu Tang^1,2, Su Xu^1,2, William L Fourney^3,4, Ulrich H Leist^3,4, Julie L Proctor^5,6, Gary Fiskum^5,6, and Rao P Gullapalli^1,2
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States, ²Core for Translational Research in Imaging @ Maryland, University of Maryland, Baltimore, MD, United States, ³Department of Mechanical Engineering, University of Maryland, Baltimore, Maryland, United States, ⁴Center of Energetics Concepts Development, University of Maryland, Baltimore, MD, United States, ⁵Department of Anesthesiology, University of Maryland, Baltimore, MD, United States, ⁶Shock, Trauma, and Anesthesiology Research Center, University of Maryland, Baltimore, MD, United States

Blast-induced traumatic brain injury (bTBI) is the hallmark injury of recent wars that includes injuries associated with underbody blasts caused by vertical acceleration. However, it is unknown if blast-induced hyper-acceleration (BIH) alone can cause bTBI in the absence of mechanical injury. This study investigated axonal alterations using in vivo DTI at 2-hours after under-vehicle BIH in rat brains using a novel recently introduced model of bTBI. Significantly elevated axial diffusivity, decreased mean and radial diffusivities were observed in multiple brain regions which indicated early axonal injury following bTBI. This unique model of bTBI can provide insights into pure underbody bTBI.

Wanyong Shin¹, Blessy Mathew¹, Katherine Koenig¹, Banks Sarah², Mark J Lowe¹, Michael Phillips¹, Michael Modic³, and Charles Bernick^2
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States, ²Lou Ruvo Center for Brain Health, Cleveland Clinic Foundatoin, Las Vegas, Nervada, United States, ³Neurological Institute, Cleveland Clinic Foundatoin, Cleveland, Ohio, United States

The Professional Fighters’ Brain Health Study (PFBHS) is a longitudinal study to monitor a cohort of active professional fighters including boxers and mixed martial arts (MMA) fighters annually over 4 years. In this study, we analyzed data from the baseline visits of 305 male boxers and MMA fighters, and ran voxelwise DTI group analysis to investigate the correlation between whole brain DTI findings and results from a computerized cognitive test battery (CNS Vital Signs). We found that transverse diffusivity in white matter is highly correlated with CNS vital measures in boxers, but not in MMA fighters. This finding might be due to the increased number of head blows in boxing, compared to MMA.

Elizabeth Imhof¹, Michael Esser^1,2, Carolyn JoAnne MacMillan¹, Richelle Mychasiuk^1,2, and Jeffrey F. Dunn^1,2
1University of Calgary, Calgary, Alberta, Canada, ²Alberta Children’s Hospital Research Institute, Calgary, Alberta, Canada

Mild traumatic brain injury and concussion are becoming increasingly recognised as a growing health problem, making it important to understand the pathophysiology and MRI metrics that correlate with injury. We studied a mild, closed head model of pediatric concussion using 9.4T MRI. Rats were imaged 24h post-injury with perfusion, T2, and T2* and anatomical scans. There was no change in quantitative metrics, confirming this is a model of mild injury. The key finding was enlargement of venous sinuses. This provides evidence for abnormal venous calibre in mTBI which highlights the needs to understand venous involvement in mTBI.

Jules Grèze^1,2, Pierre Bouzat^1,2, Jean-François Payen^1,2, Emmanuel Barbier², and Benjamin Lemasson^2
1CHU Grenoble, Grenoble, France, ²equipe 5, Grenoble Institute of Neuroscience, Grenoble, France

Post-traumatic cerebral edema in preclinical trials is usually assessed using the Apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging. One generally estimates ADC as the average value inside specific regions of interest (ROI). Parametric response map (PRM), a voxel-based analysis, is a tool to investigate spatially dispersed changes of ADC over time. It allows to detect edematous processes that are not necessarily detected by the mean ADC value approach. PRM gives some spatial and chronologic details that could distinguish different sub population based on their ADC evolution. This technique is promising in the field of traumatic brain injury.

Blessy Mathew¹, Wanyong Shin¹, Mingyi Li¹, Mark J. Lowe¹, Sarah Banks², Michael Phillips¹, Michael T. Modic¹, and Charles Bernick^2
1Cleveland Clinic, Cleveland, OH, United States, ²Cleveland Clinic, Las Vegas, Nevada, United States

From the longitudinal professional fighter's brain health study of active professional fighters, ROI based DTI result has been published to show the fight history or number of knock outs (NKO) predicts DTI changes in 74 of boxers and 81 mixed martial arts fighters (MMA). In this study, we ran voxel-wise DTI group analysis to replicate the previous finding from ROI analysis and to expand predefined ROIs to whole brain using linear and nonlinear registration methods. We conclude that, in a large cohort of subjects at risk for brain trauma, the non-linear technique is better at detecting group-level structural changes than the linear technique.

Olga Dona¹ and Michael Noseworthy^2
1Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada, ²Electrical and Computer Engineering, McMaster University, Hamilton, Ontario, Canada

Mild traumatic brain injury (mTBI) is a common condition that affects many people around the world. While some cases resolve without long-term side effects, others have to live with permanent disabilities such as learning difficulties, behavioral issues, and memory loss [1]. Conventional imaging techniques are unable to detect abnormalities in the brain of mTBI patients that have shown delayed functional response on neuropsychological evaluation. Therefore, the main objective of this study was to explore a novel analysis approach involving measurement of the temporal fractal nature of the resting state blood oxygen level depending (rsBOLD) signal

Armin Iraji¹, Hanbo Chen², Natalie Wiseman¹, Tuo Zhang², Robert Welch¹, Brian O'Neil¹, Andrew Kulek¹, Syed Imran Ayaz¹, Xiao Wang¹, Conor Zuk¹, E. Mark Haacke¹, Tianming Liu², and Zhifeng Kou^1
1Wayne State University, Detroit, Michigan, United States, ²University of Georgia, Georgia, United States

Mild traumatic brain injury is a public healthcare burden that costs the nation billions of dollars each year. Numerous data using diffusion tensor imaging have reported widely spread damage in major white matter tracts, in suggestion of large-scale network disruptions or alternations. However, very limited data investigated the scale and extent of brain network changes after mTBI. We used a novel approach to identifying the large-scale brain network alternations in both structure and function in mTBI patients at the acute stage. This work represents the first effort to investigate the scale and extent of brain network changes after mTBI.

Victoria L Morgan¹, Andrew J Gregory², and Allen K Sills^3
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Ortho-Sports Medicine, Vnderbilt University, Nashville, TN, United States,³Neurosurgery, Vanderbilt University, Nashville, TN, United States

The purpose of this work is to quantify the functional brain network changes in college student-athletes within one week of a single sports concussion compared to healthy college students. The results show that within days of injury there were focal increases in functional connectivity (FC) in parts of the default-mode network (DMN) including the bilateral hippocampus, precuneus and ventromedial prefrontal cortex. The average FC across the whole DMN linearly increased over the first week, but eventually returned to the range of the healthy subjects in three subjects. Together these results suggest a progression of DMN FC impairment and recovery.

Priya Santhanam¹, Peter Cartwright², Thomas G Perkins^3,4, Terrence R Oakes¹, John Graner¹, Gerard P Riedy^1,5, Lindell K Weaver^6,7, and William W Orrison^2,8
1National Intrepid Center of Excellence (NICoE), Bethesda, MD, United States, ²Imgen, LLC, Las Vegas, NV, United States, ³Philips Healthcare, Cleveland, OH, United States, ⁴Perkins Consultative Resources LLC, Fort Collins, CO, United States, ⁵Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States,⁶Department of Hyperbaric Medicine, Intermountain LDS Hospital and Intermountain Medical Center, Salt Lake City, UT, United States, ⁷School of Medicine, University of Utah, Salt Lake City, UT, United States, ⁸Department of Health Physics, University of Nevada Las Vegas, Las Vegas, NV, United States

This study seeks to examine alterations in brain activity during an auditory task in patients with mild traumatic brain injury (mTBI). Study participants completed a word-listening task that was presented unilaterally in each ear as well as bilaterally. Comparison of three evaluation methods (clinical radiological read, clinical computer analysis, and full GLM analysis) was performed. Radiological score and clinical computer analysis yielded a high degree of concordance, and furthermore, clinical computer analysis and GLM analysis had significant correlations. This study demonstrates the reliability and reproducibility of the task for evaluation of auditory deficits in an mTBI population.

Shiliang Huang¹, Qiang Shen¹, Lora Talley Watts¹, Justin Alexander Long¹, Wei Li¹, and Timothy Q Duong^1
1Research Imaging Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Resting state functional MRI studies have reported disrupted functional connectivity after traumatic brain injury (TBI) in humans. The types, time after injury, extent and location of TBI in humans are heterogeneous. Animal models of TBI offer a means to study the effects of injury on rsfMRI under controlled conditions. The goal of this study was to use independent component analysis (ICA) method to investigate longitudinal changes of functional connectivity in moderate traumatic brain injury in rats. Comparisons were made with functional outcomes measured by forelimb placement asymmetry and foot fault behavioral tests.

Shun Qi¹, Panli Zuo², langlang Gao¹, Ying Liu¹, Mathias Nittka³, and Hong Yin^1
1Xijing Hospital, Fourth Military Medical University, xian, shaanxi, China, ²Siemens Healthcare, MR Collaborations NE Asia, shaanxi, China, ³Siemens Healthcare, Germany, Germany

Networks of PTSD patients exhibited a less efficient organization involving decreased and increased regional connectivity compared with control subjects. Regional connections related to the fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.

Eva M Palacios¹, Alastair J Martin¹, Frank Ezekiel¹, Esther L Yuh¹, Geoffrey T Manley², and Pratik Mukherjee^1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, ²Neurological Surgery, San Francisco General Hospital, San Francisco, California, United States

Each year, an estimated 1.7 million Americans sustain traumatic brain injury (TBI), often resulting in devastating neurological disabilities. TRACK-TBI is an NIH-funded study with the goal to create a large, high quality neuroimaging and clinical database. Diffusion tensor imaging (DTI) has shown promise in prior single-center studies and a major objective of TRACK-TBI is to validate its utility. A critical need for a multicenter imaging study is to minimize the inter-site variability of quantitative neuroimaging biomarkers. In this work, we present initial results that suggest the feasibility of standardizing DTI across 3T scanners in a large-scale neuroimaging research study.

Kausar Abbas¹, Trey E Shenk¹, and Thmoas M Talavage^1,2
1Electrical and Computer Engineering Department, Purdue University, West Lafayette, IN, United States, ²Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States

The aim of this study is to characterize the differential long-term effects of sub-concussive brain injury on high school football athletes with and without a history of concussion (HoC and NoHoC). For this purpose, group differences in various graph-theoretical network measures were computed to characterize their network’s segregation, integration and resilience properties. HoC athletes exhibited significantly lower segregation than NoHoC athletes. Reduced segregation is expected with aging over healthy adult life span, thus suggesting a relatively faster aging brain for HoC athletes. HoC athletes also exhibited lower assortativity values suggesting relatively more vulnerable highly-connected brain regions.

Wen-Tung Wang¹, Dzung Pham¹, and John A Butman^1,2
1National Institutes of Health, Bethesda, MD, United States, ²Center for Neuroscience and Regenerative Medicine, MD, United States

Quantitative Susceptibility Mapping (QSM) provides unique image contrast based on differences in tissue magnetic susceptibilities. 3D single shot echo-planar imaging (EPI) with 1 mm isotropic resolution and 2D single shot EPI QSM with resolution of 1.8×1.8×2 mm3 has been demonstrated to be statistically equivalent to 3D GRE QSM at 1.5 T. In this work we applied 3D segmented EPI [4] for QSM of whole brain with anisotropic resolution and whole head with isotropic resolution at 3 T.

Kathryn Yvonne Manning¹, Arthur Brown², Robert Bartha², Gregory A. Dekaban³, Christy Barreira³, Tim Doherty⁴, Lisa Fischer⁵, Sandra Shaw⁵, Douglas Fraser⁶, and Ravi S. Menon^2
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, ²Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, ³Robarts Research Institute, London, Ontario, Canada, ⁴Physical Medicine and Rehabilitation, University of Western Ontario, London, Ontario, Canada, ⁵Primary Care Sport Medicine, Fowler Kennedy Sport Medicine, London, Ontario, Canada, ⁶Paediatrics Critical Care Medicine, London Health Sciences Centre, London, Ontario, Canada

Changes in fractional anisotropy and mean diffusivity of major white matter tracts in young hockey players after concussion. These changes remained significantly different from an independent control group 3-months post-concussion.

Eva Heckova¹, Michal Bittsansky^1,2, Stefan Sivak³, and Dusan Dobrota^1
1Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia, ²Radiodiagnostic Clinic, Martin University Hospital, Martin, Slovakia, ³Clinic of Neurology, Martin University Hospital, Martin, Slovakia

1H MRSI is a suitable in vivo technique for studying brain neurometabolism of mild traumatic brain injury patients. The motion caused by hit accompanying mTBI can lead to different acceleration of white and gray matter due to their different density. For this reason interface of these substancies can be promising region for detecting any changes caused by injury.

Kathryn Yvonne Manning¹, Gregory A. Dekaban², Christy Barreira², Sandra Shaw³, Robert Bartha⁴, Lisa Fischer³, Arthur Brown⁴, and Ravi S. Menon^4
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, ²Robarts Research Institute, London, Ontario, Canada, ³Primary Care Sport Medicine, Fowler Kennedy Sport Medicine Clinic, London, Ontario, Canada, ⁴Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada

Diffusion tensor imaging is able to detect FA and MD changes in rugby players between the beginning and end of season without any diagnosed concussion.

Wen-Tung Wang¹, Dzung Pham¹, and John A Butman^1,2
1Center for Neuroscience and Regenerative Medicine, Bethesda, MD, United States, ²Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States

Quantitative Susceptibility Mapping (QSM) offers unique, quantitative information about the magnetic susceptibility of tissues. While multi-orientation QSM can faithfully reconstruct susceptibility maps, it is computationally demanding and impractical for clinical scans. Single-orientation QSMs mitigate computational load and patient discomfort, but streak artifacts in susceptibility maps may still appear due to mathematical approximations. We propose to apply the single-orientation QSM twice, one at chin-up and the other chin-down orientation, using fast 3D segmented EPI to reduce streak artifacts while maintaining accuracy of the susceptibility measurements. The average of the two orientations substantially eliminates the artifacts as compared to a single orientation.

Amy Kuceyeski¹, Sudhin Shah², Jonathan Dyke³, Stephen Bickel⁴, Farras Abdelnour³, Nicholas Schiff⁵, Henning Voss⁵, and Ashish Raj^5
1Radiology and Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States, ²Neurology, Weill Cornell Medical College, NY, United States,³Radiology, Weill Cornell Medical College, NY, United States, ⁴Neurology, Albert Einstein College of Medicine, NY, United States, ⁵Weill Cornell Medical College, NY, United States

Subjects with severe brain injury suffer widespread deafferentation and connectivity loss across brain regions, at times resulting in disorders of consciousness. We test if parameters from a mathematical model of linear network diffusion predicting functional networks from structural networks (extracted from MRI) relate to level of consciousness in 26 severe brain injury patients. A strong Pearson’s correlation was found between level of consciousness and the model parameter describing the amount of time the predicted functional connectivity was allowed to diffuse along the structural connectivity network (r=0.79, p=0.0016). These findings invite further consideration of underlying biological mechanisms in recovery of consciousness.

Richard Watts¹, Margaret J. Eppstein², Alex Thomas³, Joshua P. Nickerson¹, Hugh Garavan⁴, Trevor Andrews^1,5, Christopher G. Filippi⁶, and Kalev Freeman^3
1Department of Radiology, University of Vermont College of Medicine, Burlington, VT, United States, ²Department of Computer Science, University of Vermont, Burlington, VT, United States, ³Department of Surgery, University of Vermont College of Medicine, Burlington, VT, United States, ⁴Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, United States, ⁵Philips Healthcare, Cleveland, OH, United States, ⁶University of Vermont College of Medicine, Department of Neurology, Burlington, VT, United States

Genetic programming (GP) was used to generate and evaluate expressions predicting symptom scores at one week following mild TBI, based on patients’ initial symptoms and changes in fractional anisotropy (FA) over a week following injury. High correlation between predicted and observed values (R²=0.916, n=36) was found. The resulting expression was linear with initial symptom score and a quadratic function of the change in FA in the splenium of corpus callosum. GP may be a useful technique to elicit such non-linear relationships in neuroimaging data.

Cerebrovascular Reactivity & Compliance

Monday 1 June 2015

Esther Warnert¹, Emma Hart², Kevin Murphy¹, Adele Babic³, Judith Hall³, and Richard Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ²BHI Cardionomics Research Group, Bristol University, Bristol, United Kingdom, ³Department of Anaesthetics and Intensive Care Medicine, Cardiff University, Cardiff, United Kingdom

It is still unclear whether the decrease in cerebrovascular compliance under stress occurs at the level of the major brain feeding arteries or of the cerebral arterioles because of the difficulty of in vivo measurement of cerebral arterial compliance in humans. In this experiment we use our novel MRI based method to measure cerebral arterial compliance to investigate the differential response of the cerebrovasculature to post exercise ischemia (PEI), which elevates blood pressure and sympathetic nerve activity. We found a decrease in compliance of the major brain feeding arteries, while compliance of arterioles distal to the Circle of Willis remained unchanged, during PEI compared to rest.

Jackie Leung¹, Junseok Kim², and Andrea Kassner^1,3
1The Hospital for Sick Children, Toronto, Ontario, Canada, ²Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, ³Medical Imaging, University of Toronto, Toronto, Ontario, Canada

Cerebrovascular reactivity (CVR) is a form of a cerebrovascular 'stress test' that offers insight into the function of cerebrovasculature and has shown applicability in the clinical assessment cerebrovascular disease. Good reproducibility has previously been shown in adults using blood-oxygen level-dependent (BOLD) MRI measures in combination with a model-free prospective end-tidal targeting (MPET) system. However, reproducibility in children using this method has not yet been established. Our study shows good within-day and between-day reproducibility of BOLD-CVR measures using the MPET that is comparable to the adult data.

Binu P Thomas¹, Virendra Mishra¹, Shin-Lei Peng¹, Hao Huang¹, and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States

WM dysfunction is typically imaged using structural MRI techniques such as DTI, magnetization transfer and T2weighted-MRI. Unfortunately, these techniques do not provide physiological information. The goal of this study is to perform a thorough examination of WM vascular physiology. WM was classified into 10 major fibers, and layers with increasing depth from the cortical surface, and their vascular response to O2 and CO2 was measured. Results suggest that with increase in depth in the WM, blood supply and reactivity of blood vessels decreases. Data also suggest that fiber tracts have their own blood supply and that reactivity of these blood vessels is different.

Sheliza Halani¹, Jonathan B Kwinta², Ali M Golestani², Yasha B Khatamian², and J. Jean Chen^1,3
1Rotman Research Institute, Baycrest, Toronto, Ontario, Canada, ²Rotman Research Institute, Baycrest, Ontario, Canada, ³Medical Biophysics, University of Toronto, Ontario, Canada

In this work, we use simultaneous BOLD-CBF acquisitions with vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR, and imposed different levels of baseline vascular tension. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to vascular tension than CBF- CVR; (ii) using a combination of vasodilatory and vasoconstrictive stimuli reduces the vascular-tension dependence of both BOLD- and CBF-CVR. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease.

Hannah Furby¹, Molly G Bright¹, Esther AH Warnert¹, Chris J Marley², Damian M Bailey², and Richard G Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ²Neurovascular Research Laboratory, University of South Wales, Pontypridd, United Kingdom

Cerebrovascular reactivity (CVR) is a potential biomarker of neurovascular health and tool for measuring the therapeutic effects of physical exercise on the brain. FMRI methods have not been used to investigate whether physical fitness can predict CVR in healthy young adults. Using PASL, hemodynamic changes in response to breath-holds were combined as a measure of CVR in young adults of varying physical fitness. CVR decreased, albeit non-significantly, in those who were physically fitter. However, BOLD and CBF measurements were significantly correlated across fitness levels, suggesting that CBF and BOLD MRI are useful tools for measuring CVR.

Kevin Sam^1,2, Boris Peltenburg², Adrian P. Crawley², Julien Poublanc², Olivia Sobczyk², Diem Pham³, David E. Crane³, Christopher J.M. Scott³, Alicia A. McNeely³, Daniel M. Mandell², Joseph A. Fisher¹, Sandra E. Black³, and David J. Mikulis^2
1Department of Physiology, University of Toronto, Toronto, Ontario, Canada, ²Department of Medical Imaging, Toronto Western Hospital, Toronto, Ontario, Canada, ³Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada

Cerebrovascular reactivity in the normal-appearing white matter was assessed by using the BOLD MRI signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide. We examined quatitative T2, diffusion, and perfusion maps in the white matter and found subtle abnormalities in these metrics that were associated with impaired cerebrovascular reactivity.

Keigo Nishi¹, Minghui Tang¹, and Toru Yamamoto^2
1Graduate school of health Sciences, Hokkaido university, Sapporo, Hokkaido, Japan, ²Faculty of Health Sciences, Hokkaido university, Sapporo, Hokkaido, Japan

Venous blood oxygenation in the resting-state fluctuates because of neuronal activity and arteriolar vasomotion driven by respiratory PaCO2 changes. These fluctuations of venous blood oxygenation at respiratory range reflect arteriolar function. Deterioration of arteriolar function can be used to diagnose dementia an early stage. To obtain information of arteriolar function, MR signals fluctuation from the sagittal sinus was measured. However, the turbulence in the sinus prevents the proper measurement of the fluctuation of blood oxygenation. We developed a method to achieve precise measurement by using blood velocity mapping, and evaluated respiratory fluctuation of blood oxygenation.

Brain perfusion, oxygenation & metabolic rate

Monday 1 June 2015

Jie Huang^1
1Department of Radiology, Michigan State University, East Lansing, MI, United States

Cerebral blood volume (CBV) is related with cerebral blood flow (CBF), and knowing this relationship may play an important role in quantitative BOLD-fMRI studies. A recent MRI study reports a sex-dependent CBV-CBF power relationship in the human visual cortex. In this study, we computed CBV for each CBF using the power function and the CBF values at both rest and activation states. Comparisons of these computed CBV values with their corresponding measured CBV values for each sex revealed significant differences (max P=0.0014), suggesting the CBV-CBF relationship may not be best characterized by the power function.

William D. Rooney^1,2, Xin Li¹, Dennis N. Bourdette³, and Charles S. Springer, Jr.^1,2
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, United States, ²Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, United States, ³Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States

The unidirectional rate constant for equilibrium capillary water efflux, k_po, has been mapped with high resolution in the normal and normal-appearing MS human brain. It is the reciprocal of the mean capillary water molecule lifetime. The rate constant k_po is greater in white matter than in gray matter. Comparison with literature spectroscopic imaging of metabolites and metabolic fluxes shows that k_po tracks the oxidative phosphorylation flux per capillary. The k_po quantity detects whole-brain compromise in early stage MS.

Damon Philip Cardenas¹, Eric R Muir¹, and Timothy Q Duong^1
1University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

High altitude sickness (experienced by mountain climbers and U2 pilots) could lead to a broad spectrum of disorders in the brain and other organs as a result of low pressure and oxygen. This research uses a custom made, MRI compatible negative pressure chamber to observe the effects of hypobaric pressure on cerebral blood flow and neurovascular reactivity to hypercapnia.

Jie Liu¹, Wanshi Zhang², Long Qian³, Mingxi Liu¹, Xianrong Xu², and Limin Meng^2
1The Fourth Military Medical University, Xi'an, Shanxi, China, ²Air Force General Hospital, Beijing, China, ³GE Healthcare China, Beijing, China

Pilots often need to face and overcome hypoxia at upper atmosphere due to low oxygen concentration and low pressure. In this study we mimicked hypoxic environment equal to 3000m altitude and obtained the CBF of the participant pilots before and after hypoxic exposure using 3D pcASL. Lower CBF values were observed in pilots after hypoxic exposure in various regions, mostly happened at right hemisphere, which might be due to that the right one is more involved in visual-space and the right hemisphere was sensitive to hypoxia, which may be related to the pilots¡¯ professional characteristics

Madhwesha Rao¹, Neil Stewart¹, Graham Norquay¹, and Jim Wild^1
1University of Sheffield, Sheffield, South Yorkshire, United Kingdom

When inhaled into the lungs, xenon dissolves in blood, and is carried to the brain via the systemic circulation, where it, crosses the blood-brain barrier and dissolves into brain tissue. 129Xe has large chemical shift providing contrast for cerebral blood, grey-matter, white-matter and lipid. In this work, using hyperpolarized xenon we measure the transfer rate of xenon from cerebral blood to brain tissue across the blood-brain barrier. The transit response of the blood-brain barrier is demonstrated and proposed as a physiological indication of intrinsic permeability to xenon.

Chou-Ming Cheng^1,2, Hsiao-Wen Chung², Jen-Chuen Hsieh^1,3, Shing-Jong Lin¹, and Tzu-Chen Yeh^3,4
1Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan, ²Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taiwan, Taiwan, ³Institute of Brain Science, National Yang-Ming University, Taiwan, Taiwan, ⁴Department of Radiology, Taipei Veterans General Hospital, Taiwan, Taiwan

Recently, the total cerebral blood flow (tCBF) and venous oxygen saturation (SvO2) levels are measured noninvasively with the MRI approaches to quantify the global cerebral metabolic rate of oxygen (CMRO2). In this research, the ROI analysis with the cardiac gating sequence is applied in healthy subjects to demonstrate the impact of fluctuated tCBF induced by cardiac pulsation on the global CMRO2 measurement.

Vitria Adisetiyo¹, Jens H. Jensen¹, Chu-Yu Lee¹, Donna R. Roberts¹, Maria V. Spampinato¹, and Joseph A. Helpern^1,2
1Radiology and Radiological Science, Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, United States, ²Neuroscience, Medical University of South Carolina, Charleston, SC, United States

The disruption of brain iron homeostasis has been implicated in many neuropathologies. Investigation of such iron-related neuropathologies may, therefore, benefit from in vivo brain iron MRI methods. Although relaxation rates R2, R2* and R2' are commonly used to measure brain iron, their limitations have been well documented. In this study, we directly compare R2* with magnetic field correlation imaging and quantitative susceptibility mapping in healthy adult brains and correlate these metrics with previously reported putative postmortem iron concentrations (CPM). All metrics significantly correlate to CPM when all brain regions are assessed together but within regions, the metrics show differential correlations.

Michael Zeineh¹, Samantha Holdsworth¹, Michael Moseley¹, and Brian Rutt^1
1Radiology, Stanford University, Stanford, California, United States

Feraheme is an intravenous ultra-small iron oxide particle potentially useful for studying neuroinflammation with MRI. Ultra-high field MRI should be exquisitely sensitive to Feraheme. However, the distribution and timecourse of Feraheme has not been explored at ultra-high field. In this study, we examined the uptake and washout of Feraheme in a single volunteer at 7T. Low signal was identified Day 1 after injection in the occipital and parietal lobes, presumbably from Feraheme within small blood vessels. This low signal only partially resolved by Day 4. The remainder of the brain demonstrated minimal if any low signal in the cortex.

Kimberly L. Desmond^1,2, Alia Al-Ebraheem¹, Rafal Janik^2,3, Wendy Oakden^2,4, Jacek M. Kwiecien⁵, Wojciech Dabrowski⁶, Kalotina Geraki⁷, Greg J. Stanisz^2,4, Michael Farquharson¹, and Nicholas A. Bock^1
1Medical Physics and Radiation Sciences, McMaster University, Hamilton, Ontario, Canada, ²Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada,³Medical Biophysics, University of Toronto, Ontario, Canada, ⁴Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ⁵Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada, ⁶Anaesthesiology and Intensive Therapy, Lublin Medical University, Lublin, Poland, ⁷Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, United Kingdom

In vivo, quantitative, T₁ and T₂ MRI maps in gray and white matter of the severely myelin-deficient Shaker rat and age-matched controls were combined with metal maps of iron and manganese obtained with synchrotron radiation X-Ray fluorescence (XRF). Given the relaxivities of the transition metals and their concentrations from XRF, it was found that a substantial proportion of 1/T₁ was due to the transition metals, and a much lesser proportion of 1/T₂. These results suggest that T₁ and T₂ could be combined to disentangle the effects of myelin, Fe and Mn in demyelinating diseases with suspected transition metal involvement.

Wendy W Ni^1,2, Thomas Christen², and Greg Zaharchuk^2
1Department of Electrical Engineering, Stanford University, Stanford, California, United States, ²Department of Radiology, Stanford University, Stanford, California, United States

R2’-based oxygenation mapping with gas challenges is a promising area of research in clinical neuroimaging. Currently, there are few published studies on reproducibility, which is a crucial factor for clinical applicability. In this study, we rigorously evaluated reproducibility and changes of two R2’ measurements in normal young subjects, using a multi-echo modified GESFIDE sequence during hypercapnia and hypoxia, with extensive concurrent physiological monitoring. We observed statistically significant reduction in R2’ during hypercapnia and slight increase during hypoxia, providing a strong platform for further MR-based studies in quantification and validation of regional brain tissue oxygenation.