Fetal & Pediatric Neuroimaging

Tuesday 2 June 2015

Richard Beare¹, Jian Chen¹, Dimitrios Alexopoulos², Christopher Smyser², Cynthia Rogers², Wai Yen Loh^1,3, Lillian Gabra Fam¹, Claire Kelly¹, Jeanie Cheong^1,4, Alicia Spittle¹, Peter Anderson^1,5, Lex Doyle^1,4, Terrie Inder⁶, Jeff Neil⁶, Marc Seal¹, and Deanne Thompson^1
1Murdoch Childrens Research Institute, Parkville, Victoria, Australia, ²Washington University in St Louis, MO, United States, ³Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia, ⁴Royal Women's Hospital, Parkville, Victoria, Australia, ⁵Paediatrics, University of Melbourne, Parkville, Victoria, Australia, ⁶Brigham and Women's Hospital, Massachusettes, United States

Tissue classification in MR scans of neonates, especially preterm neonates, is challenging and has lead to a number of different automated approaches, with varying degrees of success. One issue in previous methods has been the degree of adaptability required due to the range of pathologies observed in studies of premature infants. This project addresses the issue of providing sufficient adaptability while maintaining stability and eliminating user intervention by combining morphological methods with the well-established “unified segmentation” approach from SPM.

Borjan Gagoski¹, Huihui Ye², Stephen Cauley², Himanshu Bhat³, Kawin Setsompop², Itthi Chatnuntawech⁴, Adrian Martin^4,5, Yun Jiang⁶, Mark Griswold⁶, Elfar Adalsteinsson^4,7, P. Ellen Grant¹, and Lawrence Wald^2,7
1Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States, ²A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, ³Siemens Medical Solutions USA Inc, Charlestown, MA, United States, ⁴Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States, ⁵Applied Mathematics, Universidad Rey Juan Carlos, Madrid, Spain, ⁶Biomedical Enginneering, Case Western Reserve University, Cleveland, OH, United States, ⁷Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States

Magnetic resonance fingerprinting is a new promising technique that enables robust estimation of tissue's T1 and T2 maps even in the presence of motion. As such, MRF seems well suited for estimation of fetal tissue parameters, particularly given the random motion of the fetus. We have tested the feasibility of MRF for fetal imaging at 3T, and present our preliminary results showing estimates of T1 and T2 maps of the fetal brain at 21 weeks of gestation.

Elda Fischi-Gomez^1,2, Alessandra Griffa^1,3, Emma Muñoz-Moreno⁴, Lana Vasung², Cristina Borradori-Tolsa², François Lazeyras⁵, Jean-Philippe Thiran^1,3, and Petra Susan Hüppi^2
1Signal Processing Laboratory 5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, (VD), Switzerland, ²Division of Development and Growth. Department of Pediatrics, University of Geneva, Geneva, (GE), Switzerland, ³Department of Radiology, University Hospital Center (CHUV) and University of Lausanne (UNIL), Lausanne, (VD), Switzerland, ⁴Fetal and Perinatal Medicine Research Group, Institut d'Investigacions Biomediques August Pi i Sunyer, IDIBAPS, Barcelona, (B), Spain, ⁵Department of Radiology and Medical Informatics, Faculty of Medicine, University of Geneva, Geneva, (GE), Switzerland

In this work we characterize the modular topology of structural brain networks of children born extreme premature and/or with additional growth restrictions, and we quantify the similarity of their brain community’ structure using information theory derived metrics. In order to characterize the communities’ fingerprint in such cases, we used the consensus-clustering algorithm as a means to estimate a smooth representative group partition for each cohort.

Kiho Im¹, Alexandre Guimaraes¹, Borjan Gagoski¹, Caitlin Rollins¹, Edward Yang¹, and P. Ellen Grant^1
1Boston Children's Hospital, Harvard Medical School, Boston, MA, United States

This study aims to investigate global patterns of early cortical folding and anatomically label primary sulci in individual human fetal brains. We analyzed typically developing and polymicrogyria (PMG) fetal brains by measuring sulcal pattern similarity with normal fetal brain templates. Our sulcal pattern comparison method characterized interrelated sulcal arrangement and patterning in the global cortical area, and effectively detected abnormal global patterns of early primary sulci in PMG in both hemispheres. Our method can help to identify and quantify abnormal early cortical organization even in the third trimester of fetal life before cortical folding pattern is fully determined.

Uday Krishnamurthy^1,2, Ramtilak Gattu¹, Pavan Kumar Jella¹, Jaladhar Neelavalli^1,2, and Ewart Mark Haacke^1,2
1Department of Radiology, Wayne State University, Detroit, Michigan, United States, ²Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States

Diffusion tensor imaging (DTI) enables us to understand brain maturation and the development of myelin both in neonatal and pediatric populations. However, the same has not been extensively used for in-utero applications, largely owing to fetal motion. In this study we analyzed the feasibility of piece wise approach of acquiring the volume of interest i.e. – multiple smaller volumes to encompass the whole volume, using a short TR single shot EPI. This approach enables a DTI volume set (12-directions) to be acquired within 10 secs, which greatly reduces the possibility of data corruption due to fetal motion.

Yohan van de Looij^1,2, Meray Serdar³, Petra S Hüppi¹, Ursula Felderhoff-Müser³, Ivo Bendix³, and Stéphane V Sizonenko^1
1Division of Child Growth and Development, University of Geneva, Geneva, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Department of Pediatrics, University Hospital Essen, Essen, Germany

Cerebral white matter injury is a leading cause of adverse neuro-developmental outcome in prematurely born infants. Experimental and clinical data from the adult demyelinating disease multiple sclerosis revealed immunomodulatory and cytoprotective effects of the sphingosine-1-phosphate receptor modulating substance Fingolimod (also known as FTY720). Therefore, the neuroprotective role of FTY720 in a neonatal model of oxygen-toxicity was investigated by using high-field Diffusion Tensor Imaging (DTI), histology and protein analysis. Results provide strong evidence for a protective effect of FTY720 on oligodendrocyte in hyperoxia-induced white matter damage coinciding with microstructural ameliorations detected by DTI in later life.

Shijun Li¹, Yi Wang², Long Qian³, and Lin Ma^4
1Department of Medical Instruments, PLA General Hospital, Beijing, Beijing, China, ²Department of Stomatology, PLA General Hospital, Beijing, China,³Department of Biomedical Engineering, Peking University, Beijing, China, ⁴Department of Radiology, PLA General Hospital, Beijing, China

The current study for the first time demonstrated the disrupted topological organization in c-ASD specific to school age children using DTI. MRI scanning was performed on 21 children with c-ASD and 21 age and gender matched healthy controls. Compared with HC, decreased characteristic path length (Lp), increased global efficiency and clustering coefficient were observed in c-ASD group, while no group effects were found in other global topological patterns. Our results suggested that both the global and regional topological patterns were disrupted in c-ASD, which might provide key neuroimaging biomarkers to classify the patients with c-ASD.

Paula L Croal¹, Junseok Kim¹, Jackie Leung¹, and Andrea Kassner^1,2
1Physiology & Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada, ²Medical Imaging, University of Toronto, Toronto, Ontario, Canada

Both cerebrovascular reactivity impairment and white matter damage are observed in sickle cell disease, however the underlying vascular contributions are not understood. We observe a positive association in children with sickle cell disease between blood oxygenation level dependent (BOLD) cerebrovascular reactivity and fractional anisotropy (r2 = 0.997, p = 0.02) in the white matter of the right frontal cortex. These results may be interpreted such that impaired cerebrovascular reactivity leads to low-grade ischemic damage and resulting WM structural degradation in sickle cell disease. However, further investigation into this causal relationship is required via longitudinal studies.

Corinna M Bauer^1,2, Bang-Bon Koo³, Lauren Zajac³, and Lotfi B Merabet^1,2
1Massachusetts Eye and Ear Infirmary, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Boston University School of Medicine, MA, United States

Cortical/cerebral visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries. Despite its prevalence and breadth of impairments, very little is known about how the underlying structural and functional changes in the brain relate to the observed clinical deficits associated with CVI. This study utilizes HARDI tractography to characterize the structural connectivity deficits observed in CVI related to their specific visual deficits. NBS identified networks showing significantly decreased fiber number and step length in CVI. Our results indicate that long range pathways associated with the dorsal and ventral streams are particularly affected in CVI

JEONG-WON JEONG¹, Senthil Sundaram¹, Diane C. Chugani¹, and Harry T. Chugani^1
1Pediatrics and Neurology, Wayne State University, Detroit, Michigan, United States

Global developmental delay (GD) refers to an etiologically heterogeneous set of neurodevelopmental disorders mediated in part by multiple genetic mutations. The present study investigates whether a "maximum a posteriori probability (MAP)" classifier, a diffusion weighted imaging (DWI) tractography method, can be used to detect unique patterns in axonal language pathways, which may be correlated to different types of genetic mutations observed in children with GD.

JEONG-WON JEONG^1,2, Senthil Sundaram^1,2, Diane C. Chugani^1,2, and Harry T. Chugani^1,2
1Pediatrics and Neurology, Wayne State University, Detroit, Michigan, United States, ²Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan, United States

Pure speech delay (SD) is a common developmental disorder which, according to some estimates, affects 5-8 % of the population. Speech delay may be not only an isolated condition but can be part of a broader condition such as global developmental delay (GD). The present study investigates whether DWI-tractography based-connectome can be a new imaging tool to differentiate GD from SD in young children. The present study found that the nodal strengths of cognitive/language networks are reduced differently in children with SD and GD. These different alterations may be effective biomarkers underlying the neurocognitive and behavioral consequences commonly identified in these patients.

Zoe Englander^1,2, Jessica Sun^3,4, Laura Case⁵, Mohamad Mikati³, Joanne Kurtzberg^3,4, and Allen W Song^1,6
1Brain Imaging and Analysis Center, Duke University, Durham, North Carolina, United States, ²Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States, ³Department of Pediatrics, Duke University, Durham, North Carolina, United States, ⁴The Robertson Cell and Translational Therapy Center, Duke University, Durham, North Carolina, United States, ⁵Department of Physical Therapy, Duke University, Durham, North Carolina, United States, ⁶Department of Radiology, Duke University, Durham, North Carolina, United States

Brain connectivity changes, measured using diffusion tensor imaging (DTI), were examined in relation to changes in motor functional ability in young children with cerebral palsy (CP) undergoing therapy. Strong correlations between changes in connectivity and changes in motor function were identified. Children with greater connectivity at time of enrollment tended to have better functional outcomes. We identified that brain connectivity could serve as a biomarker for treatment efficacy in children with CP.

Gareth Ball¹, Ricardo P Monti^2,3, Paul Aljabar¹, Nora Tusor¹, Nazakat Merchant¹, Tomoki Arichi¹, Giovanni Montana^2,3, Serena J Counsell¹, and A David Edwards^1
1Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London, London, United Kingdom,²Department of Biomedical Engineering, Division of Imaging Sciences & Biomedical Engineering, King's College London, London, London, United Kingdom,³Department of Mathematics, Imperial College London, London, United Kingdom

We acquired resting state fMRI in 122 preterm infants scanned between 30 and 48 weeks gestation. Using minimum spanning trees (MSTs) as a density-independent method for network comparison, we explored the development of functional connectivity in the period leading up to the time of normal birth. We found that functional connectivity increased significantly with age and was characterised by locally dominant, and strong interhemispheric, connections from an early age. We conclude that a functional core is present in the preterm brain from mid-gestation that facilitates efficient information transfer across the cerebral network.

Lili He¹ and Nehal A. Parikh^1,2
1Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States, ²Department of Pediatrics, The Ohio State University College of Medicine, Columubs, Ohio, United States

Resting-state functional connectivity MRI is a task-free tool that can be safely performed in infants soon after birth to gain insights into functional brain networks associated with motor, cognitive, and behavioral development. In our present longitudinal study, we followed a cohort of very preterm infants soon after birth to identify the perinatal developmental windows for major resting state networks and explore their maturation through three months corrected age. We observed the presence of several important networks, resembling patterns observed in adults, in very preterm infants. Additionally, most of the networks demonstrated an increase in connection strength with advancing postnatal age.

Wenjuan Wei¹, Minghao Dong², Yan Bai³, Wei Qin², Ruwei Dai¹, Meiyun Wang³, Dapeng Shi³, and Jie Tian^1,2
1Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Science, Beijing, Beijing, China, ²School of Life Sciences and Technology, Xidian University, Xi'an, Shanxi, China, ³Department of Radiology, Henan Provincial People's Hospital, zhengzhou, Henan, China

Autism spectrum disorders (ASD) are characterized as neurodevelopmental disconnections between brain regions. We investigated the altered intrinsic anterior insular connectivity underlying social improvements using resting-state functional MRI in younger children with ASD. Our result of reduced intrinsic functional connectivity in prefrontal cortex with improved social ability in ASD children indicates that the functional connectivity with PFC in ASD children may be over-connected. Meanwhile, an increased connectivity between right anterior insular cortex with occipital-temporal region also suggests that the occipital-temporal cortex may play a compensatory role in ASD.

Kathryn Yvonne Manning¹, Darcy Fehlings², Ronit Mesterman³, Jan Willem Gorter⁴, Lauren Switzer², Craig Campbell⁵, and Ravi S. Menon^6
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, ²Department of Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada, ³CanChild Centre for Childhood Disability Research, McMaster Children's Hospital, Hamilton, Ontario, Canada, ⁴CanChild Centre for Childhood Disability Research, McMaster University, Hamilton, Ontario, Canada, ⁵Department of Paediatrics, University of Western Ontario, London, Ontario, Canada, ⁶Centre for Functional and Metabolic Mapping, University of Western Ontario, London, Ontario, Canada

A longitudinal resting state functional MRI study of children with hemiplegic cerebral palsy treated with constraint therapy. Children with unilateral sensorimotor connectivity patterns tend to improve the most, and networks become more balanced after therapy while control subjects remained unchanged.

Vincent Jerome Schmithorst¹, Jodie Votava-Smith², Vincent Lee¹, Vidya Rajagopalan², Shaheda Suleiman², Lisa Paquette², and Ashok Panigrahy^1
1Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ²Children's Hospital Los Angeles, Los Angeles, CA, United States

The effects of congenital heart defects (CHD) on early brain development are not well understood. We used graph analysis in order to better understand the impact of CHD on functional network topology in infants. Compared to healthy control neonates, CHD neonates displayed a marked decrease in segregation metrics including transitivity (p < 0.01) and modularity (p < 0.001); and smaller clustering coefficient in multiple regions mainly in the left hemisphere and greater participation coefficient in multiple regions in both hemispheres. The marked decrease in segregation in CHD neonates suggests lower short-range functional connectivity and global immature brain development.

Vincent Jerome Schmithorst¹, Ashok Panigrahy¹, Jessica Wisnowski¹, Chris Walsh², David Bellinger², Jane Newburger², and Michael Rivkin^2
1Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ²Boston Children's Hospital, Boston, MA, United States

The precise connection between brain structural/functional differences and neurocognitive deficits in patients with congenital heart defects (CHD) remains poorly understood. We applied graph analysis to DTI data acquired from adolescents born with transposition of the great arteries (d-TGA) corrected surgically in early infancy, and typically developing controls. We used statistical mediation models to more precisely delineate the relation between d-TGA, perioperative factors, global structural network topology, and neurocognitive outcomes. Differences in network topology (increased modularity and small-worldness, decreased global efficiency) mediated worse neurocognitive outcome in d-TGA patients; these effects were ameliorated by longer therapeutic hypothermia during the arterial switch operation.

Florine Dallery¹, Catherine Gondry-Jouet¹, Cyrille Capel², Anthony Fichten², Malek Makki³, Bader Chaarani⁴, Roger Bouzerar⁴, and Olivier Balédent^4
1Radiology, Jules Verne University of Picardie and Amiens University Hospital, Amiens, Picardie, France, ²Neurosurgery, Amiens University Hospital, Picardie, France, ³MRI Research Center, University Children Hospital of Zurich, Zurich, Switzerland, ⁴Imaging, Amiens University Hospital, Picardie, France

The intracranial cerebrospinal fluid (CSF) increase is frequently seen in the ventricles or in the subarachnoid spaces of children. In number of cases, morphological images can’t conclude if it is a passive or active dilatation. The aim of this work was to see if the CSF hydrodynamic can bring complementary information to study pediatric population with a CSF volume increase. This phase contrast MRI study shows the absence of correlation between the dynamic of the CSF and its volume in the global population. The CSF oscillations bring complementary information concerning the active aspect of the CSF dilatation.

Jessica L Wisnowski¹, Aaron J Reitman¹, Tai-Wei Wu², Jonathan M Chia³, Eugenia Ho¹, Claire McLean¹, Philippe Friedlich¹, Ashok Panigrahy⁴, and Stefan Bluml^1,5
1Children's Hospital Los Angeles/USC, Los Angeles, CA, United States, ²Chang Gung Memorial Hospital, Lankou, Taiwan, ³Philips Healthcare, Cleveland, OH, United States, ⁴Children's Hospital of Pittsburgh, Pittsburgh, PA, United States, ⁵Rudi Schulte Research Institute, Santa Barbara, CA, United States

MRS acquired during therapeutic hypothermia (TH) and after re-warming in neonates with hypoxic-ischemic encephalopathy demonstrated increased phosphocreatine and lower glutamate and GABA during TH relative to after rewarming. These in vivo data provide convergent evidence that the neuroprotective mechanisms of TH include decreased cerebral metabolic demand and demonstrate that MRS is not only an important diagnostic tool, but also may aid the development and evaluation of neuroprotective therapies.

Prakash Muthusami¹, Sujana Madathil², Susan Blaser³, Edgar Jaeggi², Lars Grosse-Wortmann², Shi-Joon Yoo¹, John Kingdom⁴, Edward Hickey⁵, John Sled⁶, Christopher Macgowan⁶, Steven Miller⁷, and Mike Seed^2
1Division of Cardiac Imaging, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, ²Division of Cardiology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, ³Division of Neuroradiology, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, ⁴Department of Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, Ontario, Canada, ⁵Department of Cardiovascular Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada,⁶Department of Physiology & Experimental Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, ⁷Department of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Congenital heart disease (CHD) in neonates is known to be associated with an increased risk of perioperative white matter (WM) injury. This is a prospective study to answer the question of whether a correlation exists between altered fetal hemodynamics and subsequent neonatal brain WM changes in CHD, by comparing fetal blood flows and neonatal white matter scores against healthy fetuses. The study showed reduced total and cerebral oxygen consumption in fetuses with CHD as compared to normals, as well as increased white matter T2-scores. Furthermore, a positive correlation existed between increased fetal superior vena caval flow, known to occur in hypoxic states, and neonatal brain apparent diffusion coefficient values. These results appear to suggest a role of altered fetal cerebral hemodynamics in the brain changes that occur in CHD.

Xiawei Ou^1,2, Aline Andres^3,4, Keshari M Thakali³, Kartik Shankar^3,4, and Thomas Badger^3,4
1Arkansas Children's Hospital Research Institute, Arkansas Children's Nutrition Center, Little Rock, AR, United States, ²Radiology and Pediatircs, University of Arkansas for Medical Sciences, Little Rock, AR, United States, ³Arkansas Children's Nutrition Center, Little Rock, AR, United States, ⁴University of Arkansas for Medical Sciences, AR, United States

While strong evidence links maternal adiposity with increased risk for childhood obesity and related health concerns, less is known about potential effects of maternal body composition on fetal CNS development. In this study, we employed DTI to examine brain structure in 2-week-old term infants born from normal weight and obese mothers. Our results demonstrated that infants from obese mothers have lower white matter development (as indicated by lower FA values) than those born of normal weight mothers. White matter development in newborn infants negatively correlated with maternal adiposity. The mechanisms underlying these effects and their consequences are under investigation.

Clifford Chan¹, Heather Collins¹, Patrick M O'Neil², Joshua Brown², Joseph A Helpern¹, and Andreana Benitez^1
1Department of Radiology and Radiological Sciences, Medical University of South Carolina, Charleston, South Carolina, United States, ²Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, United States

Almost 40% of middle-aged adults in the US are obese and are at 74% greater risk for developing dementia compared to normal weight peers. A higher BMI has been associated with atrophy of both gray and white matter, in regions that preferentially degenerate with age and demonstrate early pathological signs of dementing diseases. Although these observations suggest that weight loss could be an effective strategy for dementia prevention, no human studies have directly tested whether weight loss is associated with favorable brain changes measured through diffusion MRI. This preliminary study reports changes in DKI metrics before and after weight loss in obese middle-aged women.

Xiawei Ou^1,2, Aline Andres^3,4, R.T. Pivik^3,4, Mario Cleves^3,4, and Thomas Badger^3,4
1Arkansas Children's Hospital Research Institute, Arkansas Children's Nutrition Center, Little Rock, AR, United States, ²Radiology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States, ³Arkansas Children's Nutrition Center, Little Rock, AR, United States, ⁴University of Arkansas for Medical Sciences, AR, United States

Recent studies have reported associations between morbid obesity and changes in brain structure and/or function. In this study, we used voxel-based morphometry (VBM) to evaluate brain grey matter development in healthy school-aged children who are either normal weight or obese. Our results showed that obese (otherwise healthy) children had significantly lower regional grey matter volume in widespread brain regions compared to normal weight children. Whether there is a cause-effect relationship between childhood obesity and changes in brain development will need further investigation.

Normal Developing Brain

Tuesday 2 June 2015

Alyssa Mah¹, R Marc Lebel^2,3, David C Alsop⁴, Gopal Varma⁴, and Catherine Lebel^3
1Biomedical Engineering Program, University of Calgary, Calgary, AB, Canada, ²General Electric Healthcare Canada, Calgary, AB, Canada, ³Radiology, University of Calgary, Calgary, AB, Canada, ⁴Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Understanding healthy brain development is critical for studying developmental disorders. Inhomogeneous magnetization transfer (ihMT) is able to virtually eliminate signal from unmyelinated tissues, and may provide a biomarker specific to myelination, an important part of brain development. We used ihMT and MTI to characterize the white matter (WM) of healthy children aged 2-4 and 8-13 years. While qMT was significantly different in most WM areas between groups, qihMT was only significantly different in the cingulum and genu of the corpus callosum. This indicates myelination in these frontal tracts, while changes in qMT may indicate other maturation changes in macromolecular content.

Sean Deoni¹, Justin Remer¹, Douglas Dean¹, and Jonathan O’Muircheartaigh^2
1Advanced Baby Imaging Lab, Brown University, Providence, RI, United States, ²Neuroimaging, King's College London, London, England, United Kingdom

The development and maturation of the cortical myeloarchitecture is an important, yet understudied, aspect of early childhood brain development. In this work, we sought to demonstrate the ability of quantitative myelin water fraction and relaxation time imaging to investigate cortical myelination and maturation in a large cohort of healthy and typically-developing children from 1 to 6 years of age. We reveal cortical maturation profiles across this age-range for the first time, and demonstrate their consistency with prior histological data.

Bo Cao¹, Benson Mwangi¹, Khader M. Hasan², Sudhakar Selvaraj¹, Giovana B. Zunta-Soares¹, and Jair C. Soares^1
1Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States, ²Department of Diagnostic & Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, United States

The brain development index developed in this study accurately predicted individual brain development of 303 children and adolescents for their first visit with cross-validations. The brain development index was further validated with 115 subjects, who were re-scanned at the second visit after 2 years. The accuracy of this longitudinal validation with second visit scans was comparable to that of the cross-validation with first visit scans. The index captured the neuroanatomical volume changes between the two visits. The brain development index can be applied to detect individuals following an atypical neurodevelopment and at risk of developing severe psychopathology.

Elise Croteau-Chonka¹, Justin Remer², Jonathan O'Muircheartaigh³, Holly Dirks², Doug Dean III⁴, and Sean Deoni^2
1Advanced Baby Imaging Lab, Brown University, Providence, Rhode Island, United States, ²Advanced Baby Imaging Lab, Brown University, Rhode Island, United States, ³King's College London, England, United Kingdom, ⁴Waisman Center, University of Wisconsin-Madison, Wisconsin, United States

Two important neurodevelopmental processes that occur throughout infancy and early childhood are the maturation of the myelinated white matter and cortical development (including changes in thickness, surface area, gyrification, and volume). Few prior studies have investigated the relationship between these two processes. Here, we investigate these related processes for the first time in a large cohort of young children 1-6 years of age. We show that, while related, cortical thickness and adjacent white matter maturation are not proxies for one another in this age group.

Ning Ning^1,2, Yajie Hu^1,3, Xianjun Li^1,3, Qinli Sun¹, Yanyan Li¹, and Jian Yang^1,3
1Department of Radiology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Department of Nuclear medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ³Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

It aims to extract the R2* values by using an atlas-based analysis, and to evaluate the age-related R2* changes and the potentiality for monitoring iron deposition in the gray matter of the infants and preschool children. 83 subjects (age: 3 days-51 months) were examined by using an enhanced T2* weighted angiography sequence. A coregistration of R2* to high resolution 3D-T1 anatomical images was performed, and the R2* values were extracted automatically in the cerebral cortex and deep gray nuclei. R2* values showed a significant and positive correlation with age, as well as the reference of iron content. It indicated the changes of R2* values could reflect the age-related and spatial difference of the early iron deposition in gray matter, and this atlas-based analysis may be a feasible method for R2* measurement in early brain development.

Jackie Leung¹, Junseok Kim², Przemyslaw Kosinski², 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) measures the capacity of cerebral blood vessels to dilate in response to a vasoactive stimulus. Global CVR has recently been shown to change significantly during childhood and adolescence, but very little is currently known about regional changes of CVR with age. This information can refine our understanding of cerebral physiology in children. The purpose of this study was to determine whether the developmental trajectories of CVR in children are region specific. Our findings suggest that the evolution of CVR is regionally dependent, differing in both rate of change and age of peak CVR.

Binjian Sun¹, Thomas G Burns¹, Thaddeus Reece¹, Laura L Hayes¹, Kamilah Hendrix¹, and Richard A Jones^1,2
1Children's Healthcare of Atlanta, Atlanta, GA, United States, ²Emory University, Atlanta, GA, United States

In this study, we used single shot, multi-echo fcMRI data on 25 normal pediatric controls to investigate the age dependence of local and remote functional connectivity. The results show that local connectivity exhibited an age dependent decrease in the (bilateral) frontal and temporal lobes, whereas remote connectivity showed age modulated increase in the frontal-parietal network. No age dependent increases of local connectivity or age dependent decreases of remote connectity were identified. This result echoes the findings of previous graph theory based analysis which concluded that the functional networks evolve from local connections to distributed networks as brain matures.

Yajie Hu^1,2, Xianjun Li^1,2, Mengye Lyu^1,2, Yanyan Li¹, Huan Li¹, Miaomiao Wang¹, and Jian Yang^1,2
1Department of Diagnostic Radiology, The First Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

The aim of this study was to set the birth weight as a independent factor for detecting the variation of brain structural connectivity based on 3D T1WIs in neonates by the structural covariance networks analysis. The preterm and full term neonates were respectively divided into the low and normal birth weight groups (<2500g and 2500-4000g) which matched with the postmenstrual age. The results shown that the degree, global efficiency and local efficiency in brains of normal birth weight were higher than those of low birth weight whether in full-term or in preterm groups. So the birth weight maybe provide a significant influence on the network construction.

Jana Hutter^1,2, Jacques-Donald Tournier¹, Emer J. Hughes¹, Anthony N. Price¹, Lucilio Cordero-Grande^1,2, Rita G. Nunes¹, Rui Pedro A. G. Teixeira^1,2, Serena J. Counsell¹, Jesper L. R. Andersson³, Daniel Rueckert⁴, A. David Edwards^1,2, and Jo V. Hajnal^1,2
1Centre for the Developing Brain, King's College London, London, London, United Kingdom, ²Division of Imaging Sciences and Biomedical Engineering, King's College London, London, London, United Kingdom, ³FMRIB, Oxford, Oxfordshire, United Kingdom, ⁴Biomedical Image Analysis Group, Department of Computing, Imperial College London, London, United Kingdom

The developing human connectome project (dHCP) aspires to get multi-shell diffusion data with comparable resolution, high SNR and high spherical coverage than the human connectome project in 1000 infants in natural sleep. The developed sequence combines a modified pulses gradient diffusion preparation that minimizes echo time and an optimized interleaved distribution of sensitization directions and phase encoding directions in one single self-calibrating scan to optimize efficiency and produce information rich data that is tolerant of signal loss due to sporadic movements, which is a common pattern in neonates.

Yohan van de Looij¹, Justin M Dean², Alistair J Gunn², Petra S Hüppi¹, and Stéphane V Sizonenko^1
1Division of Child Growth and Development, University of Geneva, Geneva, Switzerland, ²Department of Physiology, University of Auckland, Auckland, New Zealand

Parameters derived from diffusion tensor imaging (diffusivities and fractional anisotropy) are not specific to, the tissue’s microstructure. Recently, the neurite orientation dispersion and density imaging (NODDI), estimating the microstructural complexity of neuritis has been developed. In this work we aimed to study ex-vivo brain development of a gyrencephalic specie (sheep brain) at different gestational ages by using DWI acquisition at 9.4T fitted with the NODDI model. NODDI modelling leads to more specific markers of the tissue’s microstructure development and will be of high interest to study gyrified models of perinatal brain injury as well as in clinical practice.

Ileana O. Jelescu¹, Jelle Veraart¹, Vitria Adisetiyo¹, Sarah Milla¹, Dmitry S. Novikov¹, and Els Fieremans^1
1Center for Biomedical Imaging, Dept. of Radiology, NYU Langone Medical Center, New York, New York, United States

White matter microstructural changes during the first three years of healthy brain development are characterized using two models developed for limited clinical diffusion data: White Matter Tract Integrity (WMTI) metrics and Neurite Orientation Dispersion and Density Imaging (NODDI). Both models reveal a non-linear increase in intra-axonal water fraction and in tortuosity of the extra-axonal space as a function of age, in the genu, splenium and posterior limb of the internal capsule. The changes are consistent with myelination and asynchrony of fiber development. The quantitative differences in parameter estimates between models are explained by each model's assumptions and consequent biases.

Nicolas Kunz¹, Juliane Schneider², Lana Vasung³, Hui Zhang⁴, Patrick Hagmann⁵, Anita C Truttmann², François Lazeyras⁶, and Petra Susan Hüppi^3
1CIBM-AIT, EPFL, Lausanne, Vaud, Switzerland, ²Unit of Neonatology and Follow up, Department of Pediatrics, Centre hospitalier universitaire Vaudois (CHUV), Vaud, Switzerland, ³Division of Development and Growth, Dept of Pediatrics, University of Geneva, Geneva, Geneva, Switzerland, ⁴Computer Science, University College London, London, United Kingdom, ⁵Department of Radiology, Centre hospitalier universitaire Vaudois (CHUV), Vaud, Switzerland,⁶Department of Radiology-CIBM, Geneva University Hospitals (HUG), Geneva, Switzerland

In this work, we investigate in a cohort premature neonate born before the 30th weeks of gestation over multiple time points (31st, 35th and 40th of gestational age) the changes of the intra-axonal volume fraction (ficvf) and orientation dispersion index (ODI) of the NODDI biophysical diffusion compartment model. ficvf shows stronger correlation with age than conventional FA, whereas ODI did not show any significant changes with development. It suggests an increase of the axonal space (in preparation for myelination), with a preservation of the global organization of the newborn white matter tracts.

Yi-Shin Chang¹, Julia P Owen¹, Nicholas J Pojman¹, Tony Thieu¹, Polina Bukshpun¹, Mari Wakahiro¹, Jeffrey Berman², 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, Pennsylvania, United States

In this study, we apply NODDI in healthy controls ages 7-63 to investigate changes of fiber orientation index (ODI) and neurite density index (NDI) with brain maturation, with comparison to standard DTI metrics. Our results reveal that, while NDI increases rapidly in childhood and more slowly in adulthood, ODI increases more slowly in childhood, and accelerates in adulthood. These results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA during late adulthood is driven by the exponential rise of ODI that overcomes slower increases of NDI.

Zheng Wang¹, Qinying Jiang¹, Qiming Lv¹, Dazhi Yin¹, and Zhuangming Shen^1
1Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, Shanghai, China

With an enhanced gradient insert system (80mT/m),we conducted high angular resolution diffusion spectrum imaging on anesthetized monkeys,compared the white matter infrastructure of young (4-8 years old) and aged (20-25 years odl) monkeys and identified vulnerable aging regions of monkey brains.

Chen Jin¹, Alexandre Castonguay², Julie Tremblay¹, Philippe Pouliot^2,3, Irene Londono¹, Frédéric Lesage^2,3, and Gregory A. Lodygensky^1,3
1Research Centre CHU Sainte-Justine, Montreal, Quebec, Canada, ²École Polytechnique de Montréal, Montreal, Quebec, Canada, ³Montreal Heart Institute, Montreal, Quebec, Canada

High resolution DTI combined with TBSS allows for a systematic and automated approach to assess inflammatory white matter injury in a neonatal rat model. Animals received either intracerebral LPS or saline injections at 3 days of age. Ex vivo DTI was performed on whole extracted brains at 24 days of age, followed by TBSS on FA maps. We found an increased fractional anisotropy in the contralateral external capsule, which possibly reflects an increased plasticity following neonatal white matter injury. Understanding underlying changes behind FA increase is underway using depth-resolved optical coherence tomography imaging.

Yanyan Li¹, Xianjun Li^1,2, Jie Gao¹, Qinli Sun¹, Huan Li¹, and Jian Yang^1,2
1Department of radiology, the first affiliated hospital of medical college, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, Shaanxi, China

No studies have specifically investigated that if the birth weight as an independent index would influence the white matter development in neonates. This diffusion tensor study demonstrated that increment of birth weight is related to significant increase of FA and decrease of MD and RD in projection fibers (internal capsule and corona radiata), commissural fibers (corpus callosum) and association tracts (arcuate fasciculus) by using the tract-based spatial statistics with postmenstrual age as a covariate. The results demonstrated that the birth weight as an independent factor exerted the positive effects on neonatal white matter development.

Xianjun Li^1,2, Jie Gao¹, Qinli Sun¹, Yanyan Li¹, Huan Li¹, Mingxi Wan², and Jian Yang^1,2
1Radiology Department of the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

The purpose of this study was to compare the performances of the single-compartment and the two-compartment parameters of diffusion kurtosis imaging (DKI) in assessing the axon growth. In this study, 22 healthy term neonates (11 males and 11 females) and 22 healthy adults (11 males and 11 females) were examined. Fourteen regions of interests (ROIs) were selected by using the atlas-based analysis. Inter-group differences of the regional values were tested by using the Wilcoxon Signed Rank Test. This DKI study investigated changes of the intra-axonal and extra-axonal diffusivities, as well as the single-compartment fractional anisotropy (FA) through the comparison between the neonates and adults. FA increased by 105.16 % in the adults, compared with that in neonates. The relative decrease of extra-axonal radial diffusivity was 24.88 %. Few significant changes of extra-axonal axial diffusivity were found. Intra-axonal diffusivity demonstrated largest relative changes in adults (261.21 %). This result was in agreement with the fact that the myelinated axon was more than twice the axon caliber of the unmyelinated axon. In conclusion, the intra-axonal diffusivity was a sensitive biomarker for the assessment of the axon growth. White matter model for DKI provided more detail information for investigating the white matter development.

Jessica Dubois^1,2, Cyril Poupon³, Bertrand Thirion^2,4, Sofya Kulikova⁵, François Leroy^1,2, Lucie Hertz-Pannier⁵, and Ghislaine Dehaene-Lambertz^1,2
1Cognitive Neuroimaging Unit, INSERM, Gif-sur-Yvette, France, ²NeuroSpin, CEA, Gif-sur-Yvette, France, ³NeuroSpin, UNIRS, CEA, Gif-sur-Yvette, France,⁴Parietal, INRIA, Gif-sur-Yvette, France, ⁵NeuroSpin, UNIACT, U1129, INSERM-CEA, Gif-sur-Yvette, France

To understand how perisylvian regions collaborate from the preterm period on, we investigated the development of the language network bundles during the first stages of language acquisition. Using diffusion imaging, tractography and DTI parameters in 6- to 22w-old infants, we demonstrated structural similarities between infants and adults in the organization and microstructure of white matter bundles, especially with a segregation between dorsal and ventral pathways. According to normalized transverse diffusivity, we further highlighted the developmental calendar of these bundles: the ventral pathway starts maturing before the dorsal pathway, nevertheless the dorsal maturation catches up during the first post-natal months.

Virendra Mishra¹, Tina Jeon², Mihovil Pletikos³, Nenad Sestan³, and Hao Huang^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Texas, United States, ³Department of Neurobiology, Yale University, CT, United States

The formation of human brain connectome in the fetal stage is poorly understood. Both fetal axons and transient glial fibers exist in the fetal brain. In this study, we aimed to explore the role of the glial fibers in constructing human brain connectome in the fetal stage. High resolution DTI data was acquired from ex vivo fetal brains at 13 weeks of gestation (wg), 15wg, 17wg and 19wg. Based on DTI tractography and cortical parcellation, brain network properties based on graph theory were measured with the connectivity contributed by glial fibers only, axons only and both glial fibers and axons.

Da Shi^1,2, Jiachen Zhuo^1,2, Su Xu^1,2, Jaylyn Waddell³, and Rao P Gullapalli^1,2
1Core for Translational Research in Imaging at University of Maryland, University of Maryland School of Medicine, Baltimore, MD, United States, ²Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ³Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States

The frontal lobe is an integral competent of the limbic system that governs emotion, motivation, reward and memory. The development of the frontal lobe showed different trajectories between males and females, consistent with findings of differences in overall brain volume between male and female. This study measured structural connectivity, an indication of physical connections within and between brain regions, in the developing frontal lobe of male and female mice. Differences in structural connectivity were revealed mainly in cortical regions during periods of synapse overproduction and pruning in male and female mice, but not between white matter to cortical regions.

Qinli Sun¹, Xianjun Li^1,2, Yanyan Li¹, Jie Gao¹, Huan Li¹, and Jian Yang^1,2
1Department of Diagnostic Radiology, The First Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

In this study, we compare the sensitivity between diffusion tensor and kurtosis metrics on detecting the changes of the cerebral gray matter nuclei between health neonates and young adults. Twenty-two term neonates and twenty-two young adults underwent diffusional kurtosis imaging. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), Mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK) were calculated in four cerebral gray matter nuclei including thalamus, putamen, globus pallidus and caudate nucleus. There were significant differences for all seven parameters between neonates and adults in four GM regions (p<0.05), except AD in thalamus(p=0.944). The relative change of the kurtosis metrics varied from 82.86% to 210.81% while that of diffusion tensor metrics just from 1.45% to 70.59%. The kurtosis metrics had bigger variations than those in the diffusion tensor metrics. DKI offers a more comprehensive and sensitive characters for detection of microstructural changes by measuring directionally specific diffusivity and kurtosis, and has the potential to explore the development process of gray matter.

Virendra Mishra¹, Kenichi Oishi², Hang Li^1,3, Tina Jeon¹, Minhui Ouyang¹, Lina Chalak⁴, Jonathan M Chia⁵, Yun Peng³, Nancy Rollins⁶, Susumu Mori², and Hao Huang^1,7
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ³Department of Radiology, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China, ⁴Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ⁵Philips Medical Systems, Dallas, Texas, United States, ⁶Department of Radiology, Children's Medical Center at Dallas, Dallas, Texas, United States, ⁷Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

From 30 weeks of gestation (wg) to normal time of birth (40wg), human brain maturation results in dramatic structural alterations. These dramatic structural differences make it difficult and presumably inaccurate to adopt a single atlas for MRI and DTI acquired from preterm brains in the age range of 30wg to 40wg. In this study, we aimed to establish population-averaged age-specific DTI templates of preterm human brains at 33wg, 36wg and 39wg. We further evaluated these age-specific DTI templates by showing statistically significant and inhomogeneous local expansions with transformations of younger preterm brains to the templates of older brains.

Tina Jeon¹, Austin Ouyang¹, Virendra Mishra¹, Alejandra Perez¹, Lina Chalak², Jonathan Chia³, Muraleedharan Sivarajan², Nancy Rollins⁴, and Hao Huang^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, ²Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas, United States, ³Philips Medical Systems, Dallas, Texas, United States, ⁴Department of Radiology, Children's Medical Center at Dallas, Dallas, Texas, United States

From the early 3rd trimester to around birth, the cerebral cortex undergoes rapid microstructural changes. Decreases of fractional anisotropy (FA) derived from DTI in cerebral cortex during this developmental period have been well documented in the literature. Mean kurtosis (MK), derived from diffusion kurtosis imaging (DKI), quantifies restricted water diffusion in the cerebral cortex and offers complementary information on cortical microstructural development. In this study, we aim to gain more comprehensive insight into regional microstructural changes of cerebral cortex by combining DKI and conventional DTI of the preterm human brains.

Austin Ouyang¹, Qiaowen Yu², Virendra Mishra¹, Lina Chalak³, Tina Jeon¹, Jonathan M Chia⁴, Muraleedharan Sivarajan³, Nancy Rollins⁵, Shuwei Liu², and Hao Huang^1,6
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Shandong, China, ³Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁴Philips Healthcare, Cleveland, Ohio, United States, ⁵Department of Radiology, Children's Medical Center, Dallas, TX, United States, ⁶Department of Radiology, University of Texas Southwestern Medical Center, TX, United States

Structural characterization of white matter (WM) maturational processes from mid-fetal stage to normal time of birth is critical for understanding not only the normal development of WM tracts but also the clinical implications associated with abnormal WM development such as PVL. With high resolution DTI of early developing brains at 20wg, 35wg and 40wg, establishment of population-averaged age-specific template, WM skeleton extraction and DTI-based tractography of individual WM tracts, we aimed to understand the spatiotemporally heterogeneous microstructural and macrostructural development of individual WM tracts, including myelination, axonal packing and volume growth, from mid-fetal stage to normal time of birth.

Neuroanatomy & Tissue Characterization

Tuesday 2 June 2015

Neville D Gai¹ and John A Butman^1
1Radiology & Imaging Sciences, NIH, Bethesda, MD, United States

Contrast enhanced MRI (CE-MRI)of the brain is routinely used to identify lesions and for staging treatment therapy. 3D T1-w turbo spin-echo (TSE) sequence provides a valuable contrast mechanism. However, identification of contrasting tissue can be hampered by neighboring enhancing vascular signal (VS). Typically, a preparation sequence is used to reduce the vascular signal. In this work, we study the application of vascular crushing gradients (VCG) along all axes integrated into the 3D T1 TSE sequence to reduce enhancing vasculature. Such a sequence is advantageous in reducing scan time as well as providing continuous reduction in VS. Evaluation of VS in CE-MRI images showed a large reduction in VS with a minor reduction in SNR after introduction of VCG.

Xinqiang Yan^1,2, Jan Ole Pedersen³, Long Wei², Xiaoliang Zhang⁴, and Rong Xue^1
1State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, Beijing, China, ²Key Laboratory of Nuclear Analysis Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, Beijing, China, ³Sino-Danish Center, University of Chinese Acaemy of Sciences, Beijing, Beijing, China, ⁴Department of Radiology and Biomedical Imaging, University of California San Francisco and UCSF/UC Berkeley Joint Graduate Group in Bioengineering, San Francisco, California, United States

The length of microstrip transceiver arrays is often constrained by the required resonant frequency, limiting the image coverage. To increase the imaging coverage and also improve its parallel imaging capability, we designed, constructed and tested a 16-channel double-row microstrip transceiver array for human head imaging at 7T. In the comparison study with a regular single-row array, the double-row array demonstrated a larger imaging coverage along z-direction and improved parallel imaging capability. The proposed technique is particularly suitable for the design of large-sized transceiver arrays with large channel counts.

Xinqiang Yan^1,2, Long Wei², Rong Xue¹, and Xiaoliang Zhang^3
1State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, Beijing, China, ²Key Laboratory of Nuclear Analysis Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, Beijing, China,³Department of Radiology and Biomedical Imaging, University of California San Francisco and UCSF/UC Berkeley Joint Graduate Group in Bioengineering, San Francisco, California, United States

Traditional decoupling methods face technical challenges in designing monopole arrays. In this study, we investigate the possibility of using the induced current elimination (ICE) decoupling for cylindrical shaped monopole arrays. To evaluate the method, an eight-channel transceiver monopole array, suitable for human head imaging at 7T, with the ICE decoupling method was built and comparatively investigated. Studies demonstrated that isolation between adjacent monopole elements was improved from -7.1 dB to better than -25 dB by using this method. Compared with the monopole array using no decoupling methods, the ICE-decoupled monopole array had a higher SNR and better parallel imaging ability.

Uehwan Kim¹ and Hyunwook Park^1
1Department of Electrical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea

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Shubharthi Sengupta¹, Mark van Zandvoort², Dean Paes², Ralf Galuske³, Rainer Goebel¹, and Alard Roebroeck^1
1Dept. of Cognitive Neuroscience, Maastricht University, Maastricht, Netherlands, ²Maastricht University, Netherlands, ³Fachbereich Biologie, Technische Universität Darmstadt, Germany

Investigation of small human tissue samples at ultra-high fields has involved the use of existing preclinical gradient and RF coil systems to realise important information about fundamental neuroanatomy at the mesoscale. We test extending high resolution post-mortem diffusion MRI to larger tissue samples by using large-bore human 9.4T MRI system and as a proof of concept designed and built a 9.4T coil for imaging moderately sized specimens that fit a 4cm Petri dish. We aim to achieve white and gray matter fiber orientational modelling from diffusion MRI at 300um in a cat brain sample, which would be difficult to achieve using a larger coil designed for human in-vivo imaging.

Arsene Longin Ella¹ and Matthieu Keller^1
1Department of Reproductive Physiology and Behavior, INRA - Centre Val de Loire UMR 7247 - CNRS - University of Tours – IFCE, Nouzilly, Tours, France

Sheep is a developing animal model used in the field of neurosciences, but still rather limited in MRI where a brain template image does not exist. We proposed to: i) compute high resolution T1W and T2W in-vivo sheep brain templates and prior probability maps of GM, WM and CSF using optimized non-linear registration; ii) use prior maps to extract CNS structures. The goodness of fit throughout the registration led to build templates in accordance with single images. Non-linear prior maps allowed highlighting deep brain structures and opened the possibility to use them in the construction of a sheep brain atlas.

Clive R Rosenthal¹, Thomas D Miller¹, Tammy W C Ng², Stuart Golodetz³, Christopher Kennard¹, and Penny A Gowland^4
1Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²Department of Anaesthesia, Univerisity College London Hospital, London, London, United Kingdom, ³Computer Science, University of Oxford, Oxford, Oxfordshire, United Kingdom, ⁴Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Reliable in vivo identification of human hippocampal (Hc) subfields remains a significant challenge. Here, we quantified human Hc subfields along the transverse axis at an unprecedented resolution (0.4 x 0.4 x 0.1 mm). Subfield volumes in 12 healthy adults yielded distributions consistent with histological data, whereas volumes were significantly reduced in three adults with bilateral hippocampal amnesia. Dice indices were high, indicating that the protocol was suited to reliable delineation of Hc subfields in health and in disease. The results demonstrate that in vivo 3D-FSE 7.0-Tesla neuroimaging can be administered to test whether Hc pathology is manifest in specific subfields.

Gosuke Okubo¹, Tomohisa Okada¹, Akira Yamamoto¹, Mitunori Kanagaki¹, Yasutaka Fushimi¹, Tsutomu Okada¹, and Kaori Togashi^1
1Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

We evaluated magnetization prepared 2 rapid gradient echoes (MP2RAGE) imaging for deep gray matter segmentation compared with conventional MPRAGE imaging and reproducibility of T1 maps. MP2RAGE has high reproducibility and better tissue contrast than MPRAGE in deep gray matter, except lateral thalamus. T1 map derived from MP2RAGE was considered highly reliable. MP2RAGE is considered useful for measurement and analysis of the deep GM.

Claude J. Bajada¹, Hamied A. Haroon², Hojjatollah Azadbakht², Geoff J. M. Parker², Matthew A. Lambon Ralph¹, and Lauren L. Cloutman^1
1Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester, Manchester, United Kingdom, ²Centre for Imaging Science, Institute of Population Health, The University of Manchester, Manchester, United Kingdom

Diffusion tractography is the only method available to study the brain’s white matter anatomy in-vivo, however, it does not provide accurate information about the terminations of white matter tracts. This poster presents a method to extract white matter tract terminations (ExTracT) using tractography, and illustrates the method by performing the technique on the temporal lobe. The results demonstrate that ExTracT is capable of reliably identifying voxels near the brain’s surface that contribute to a tract, enabling the generation of tract termination maps. These termination maps can be used to improve basic white matter anatomical knowledge in health and disease.

Frank Q Ye¹ and Xiaomin Yue^2
1Neurophysiology Imaging Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States, ²Laboratory of Brain Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States

Imaging cortical myeloarchitechture in-vivo is valuable for study brain anatomy and functional organization. With improved spatial resolution and sensitivity, T1 imaging may allow precise mapping of cortical myelination distribution and reveal subtle abnormalities underlying developmental brain disorders. We report here a high resolution imaging protocol optimized for anesthetized rhesus monkey studies. The sensitivity and resolution provided by our implementation afford us to observe the V2 CO stripes, a known architectonic features that have been visible in histology but have not been observed previously using MRI in a living brain.

Khader M Hasan¹, Zafer Keser², Arash Kamali³, Nuray Yozbatiran², and Gerard E Francisco^2
1Diagnostic and Interventional Imaging, University of Texas Health Science Center, Houston, Texas, United States, ²Physical Medicine and Rehabilitation, University of Texas Health Science Center and TIRR NeuroRecovery Research Center, Houston, Texas, United States, ³Department of Diagnostic Radiology, Division of Neuroradiology, Johns Hopkins University, Maryland, United States

In this study, we demonstrate the feasibility of in vivo delineation and 3D reconstruction of the main cerebellar pathways using high resolution diffusion tensor imaging (DTI) data on 3.0 T in a systematic way. We also identified and quantified bilaterally each tract volume and its corresponding DTI scalar metrics. Although these tracts have been described previously, a clear deterministic tractography protocol to reconstruct all these tracts and their corresponding DTI attributes has not been reported.We believe that revealing the connections of cerebellum with extracerebellar structures is a crucial step in understanding underestimated roles of cerebellum.

Yohan Yee^1,2, Jacob Ellegood², and Jason P Lerch^1,2
1Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ²Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada

Anatomical covariance networks (ACNs) are networks of covariances in brain region volume. Mouse ACNs were computed between eight seed regions and the rest of the brain voxelwise through high-resolution MR images of >100 mice brains and compared to structural connections determined via Allen Brain Institute tracer experiments. We show that ACNs significantly correlate with fiber projections, thus providing another way to assess brain connectivity. ACNs were generally bilateral. Correlating the ACNs for each seed to tracer injection images gave a distribution of correlation coefficients with mean 0.176, which is highly significant under the null distribution obtained through a permutation test.

Mu Lin¹, Hongjian He¹, Congyu Liao¹, and Jianhui Zhong^1
1Center for Brain Imaging Science and Technology, Zhejiang University, China, Hangzhou, Zhejiang, China

The g-ratio is equal to the ratio between axon diameter and fiber diameter (axon plus myelin sheath). Previous studies have shown that g-ratio can be a potential biomarker for white matter that is sensitive to the process of demyelination and remyelination after disease, as well as sex differences in the brain development of adolescences. We propose a noninvasive way to estimate g-ratio. To validate the accuracies of our method, we simulate the effect of multi-component T2 and diffusion on g-ratio with a three-compartment Monte Carlo model.

Se-Hong Oh¹, Jiwon Nam², Joon Yul Choi², and Jongho Lee^2
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ²Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea

In this study, a whole brain population-averaged aMWF map (n = 33; 35.3 ¡¾ 9.9 yo) was generated using a new myelin water imaging sequence (ViSTa). This map provides the spatial distribution of myelin content and may serve as a template to compare myelin concentration differences among different groups.

Niels Bergsland^1,2, Maria Marcella Laganà¹, Eleonora Tavazzi¹, Francesca Baglio¹, Paola Tortorella¹, Matteo Caffini², Mario Clerici¹, Giuseppe Baselli², and Marco Rovaris^1
1IRCCS, Fondazione Don Gnocchi, Milan, MI, Italy, ²Dipartimento di Elettronica, Informatica e Bioingegneria, Politecnico di Milano, Milan, MI, Italy

The relationship between cortical morphology and anatomically/functionally connected white matter tracts has not been widely studied in healthy subjects. We used FreeSurfer to reconstruct the primary motor cortex (PMC) from 3D-T1 MRI. Diffusion tensor imaging was used to assess measures of corticospinal tract (CST) integrity. Controlling for age, sex and intracranial volume, diffusivity coefficients within the CST were moderately to strongly correlated with PMC surface area, but not thickness nor curvature. The neural underpinnings of these relationships remain to be elucidated.

J. Keiko McCreary¹, L. Sorina Truica¹, Ashlee Matkin², Albert R. Cross³, David M. Olson⁴, and Gerlinde A. S. Metz^1
1Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada, ²Faculty of Medicine, University of Alberta, Alberta, Canada, ³Departments of Physics and Neuroscience, University of Lethbridge, Alberta, Canada, ⁴Departments of Obstetrics & Gynecology, Pediatrics and Physiology, University of Alberta, Alberta, Canada

This study investigated the effects of maternal inflammation and stress on offspring neurodevelopmental trajectories. We used in vivo magnetic resonance imaging (MRI) to analyze maps of transverse relaxation times (T2) to provide a quantitative measure of brain tissue changes in an animal model of maternal stress and inflammation induced by IL-1B treatment. The MRI findings, confirmed by histology, indicate that exposure to IL-1B and stress during gestation causes an increase in neuronal density in cortical layers I-III. This could reflect disturbed neuronal pruning during brain development, which represents a prominent neuropathological finding in human neurodevelopmental disorders.

Leigh Spencer Noakes¹, Brian J. Nieman^1,2, Ellen van der Plas³, Shoshana Spring¹, and Russell Schachar^4
1Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada, ²Medical Biophysics, University of Toronto, Toronto, Ontario, Canada,³Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada, ⁴Psychiatry, University of Toronto, Toronto, Ontario, Canada

Chemotherapy is used to treat the most common childhood cancer, acute lymphoblastic leukemia (ALL), with a success rate of 90%. Unfortunately, survivors are at high risk of developing “late effects”, which are prominent in children and cause slowed learning as well as other cognitive effects. The goal of this project is to determine if a portion of the population can be identified prior to treatment as sensitive to methotrexate treatment by genetic testing combined with MRI analysis of brain during development.

Jason P Lerch^1,2 and Jan Scholz^1
1Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada, ²Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

We present a method to decompose the hippocampus into anatomically informative shape measures, including the length and thickness of the stratum radiatum, stratum oriens, and pyramidal cell layer. Similar measures are applied to the dentate gyrus. This method is initially applied to mouse imaging data.

Kirsten Mary Lynch¹, Arthur Toga¹, and Kristi Clark^1
1Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, United States

This study aims to elucidate in vivo correlations of diffusion imaging parameters in order to yield biologically relevant microstructural information. Here, we use diffusion imaging parameters to (1) characterize the underlying neuronal cytoarchitecture and columnar organization of defined cortical regions and (2) determine how these parameters change with age. We relate regional variations in cortical thickness to mean diffusivity and NODDI microstructural parameters (orientation dispersion index and intra-neurite volume fraction), to better characterize local microscopic neural organization in vivo. Our results show that dMRI measures are sensitive to the microstructural differences between anatomically-defined regions of functional significance throughout development.

Jing Guo¹, Tonia Munder², Charlotte Klein², Anna Pfeffer², Jürgen Braun³, Barbara Steiner², and Ingolf Sack^1
1Radiology, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, ²Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, ³Department of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany

We applied MRE to study the viscoelasticity of the hippocampus in the mouse, and examined the changes in tissue mechanical property under the influence of enriched environment (EE). In normal mouse brain, we found that hippocampus tissue is more elastic and less viscous compared to the rest of the brain. We also observed an increase in G″ (viscosity) in mice exposed to an enriched environment, which might relate to newborn neurons which are not yet fully integrated into the neuronal network.

Yohan van de Looij^1,2, Vanessa Ginet¹, Petra S Hüppi¹, and Stéphane V Sizonenko^1
1Division of Child Growth and Development, University of Geneva, Geneva, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Lactoferrin (Lf) is an iron-binding glycoprotein secreted in milk known as antioxydant, anti-inflammatory and antimicrobial. The aim of this work was to assess by neurite orientation dispersion and density imaging the neuroprotective effects of Lf during lactation on 3 days-old pup rats (corresponding to human preterm born at 24-28 weeks of gestation) injected with Lipopolysaccharide (LPS) in the corpus callosum. Results show a neuroprotection of Lf supplemented in food during lactation following LPS exposure with less altered microstructure.

Xiang Feng¹, Andreas Deistung¹, Ferdinand Schweser^2,3, Daniel Guellmar¹, and Juergen R. Reichenbach^1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany,²Buffalo Neuroimaging Analysis Center, Dept. of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States, ³MRI Molecular and Translational Imaging Center, Buffalo CTRC, State University of New York at Buffalo, Buffalo, NY, United States

Image contrast and registration are two important issues that determine the success of FMRIB's Integrated Registration and Segmentation Tool (FIRST). The purpose of this study was to investigate automated segmentation of deep gray matter nuclei using FIRST depending on image contrast and registration accuracy of the individual data to MNI space.

Yue Li¹, Can Ceritoglu², Hangyi Jiang³, Anthony E. Kolasny², Timothy J. A. Brown², Xiaoying Tang², Zifei Liang^3,4, Andreia V. Faria³, Marc Vaillant⁵, Naveen Santhanam⁵, Xin Li³, Susumu Mori³, and Michael I. Miller^2
1AnatomyWorks, LLC, Baltimore, Maryland, United States, ²Center for Imaging Science, Johns Hopkins University, Baltimore, Maryland, United States,³Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ⁴Department of Electronics and Information Engineering, Sichuan University, Chengdu, Sichuan, China, ⁵Animetrics, Inc, Conway, New Hampshire, United States

Brain geodesic positioning system (BrainGPS, https://braingps.mricloud.org) is a web-based platform for neuroimage research community. Using web services, users can submit data, monitor the processing job status, browse and download results online. It provides image analysis tools including a comprehensive, multi-atlas processing pipeline that segments MPRAGE data into 286 structures at five granularity levels, and a comprehensive DTI processing pipeline including quality control, tensor calculation and segmentation. Its visualization tool provides highly-interactive interface to examine the analysis result, both in 2D and 3D. The built-in database of control subjects for age 8–90 allows age-matched interpretation of each result.

Yong Pang¹, Daniel B. Vigneron^1,2, and Xiaoliang Zhang^1,2
1Dept of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²UCSF/UC Berkeley Joint Graduate Group in Bioengineering, San Francisco & Berkeley, CA, United States

The interpolated Compressed Sensing method is able to reduce the image error and increase contrast-to-noise ratio (CNR) for multi-slice two-dimensional MR imaging. In this study we developed the iCS method in phase encoding direction to facilitate its practical implementation for brain imaging, making it easier to meet the requirement of the gradient slew rate and maximum amplitude.

Advanced Neuroanatomy & Morphometry

Tuesday 2 June 2015

Jinghua Wang¹, Lili He², and Zhong-Lin Lu^1
1Center for Cognitive and Behavioral Brain Imaging, The Ohio State University, Columbus, Ohio, United States, ²Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Ohio, United States

Magnetization-prepared rapid gradient echo sequence has been widely used for classifying brain tissues in voxel-based morphometry, detecting pathological changes of the brain, estimating regional brain volume abnormalities, assessing brain development, and evaluating treatment or therapeutic responses. Over years, many attempts have been made to optimize the sequence to improve image quality with whole brain coverage in shorter scan time. In this study, we evaluate the signal-to-noise ratio and GM-WM contrast-to-noise ratio acquired using four different sets of optimized parameters recommended by different institutes.

Wanyong Shin¹, Taehoon Shin², Sehong Oh¹, and Mark J Lowe^1
1Imaging Institute, Cleveland Clinic Foundatoin, Cleveland, Ohio, United States, ²Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States

While MP2RAGE has shown the potential to generate B1 insensitive T1 contrast over brain tissue at high fields, the long scan time (> 8 mins) is undesirable practically. However, the long TR (> 6s) is essential to provide the large dynamic range of apparent T1 relaxation for dual MP2RAGE acquisitions. We propose z-direcitonal accelated MP2RAGE, which provides the increased flip angle with the similar dynamic recovery as z-directionally non-accelearted MP2RAGE. Simulation was conducted to optimize MP2RAGE paramenters and a healthy subject was scanned with the optimized parameters at 7T. The improved SNR and CNR with z-direcitonal accelated MP2RAGE acclerate scan time under 5 mins with isotropic 1mm3 voxel size.

Linqing Li¹, Moises Hernandez¹, and Peter Jezzard^1
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

DANTE pulse trains can be used to suppress moving blood signal with minimal impact to the static tissue signal. We introduce an inversion recovery prepared 3D DANTE-FLASH (denoted as ‘IR-DASH’) that is able to generate 1 mm isotropic resolution full brain images with attenuated fluids (arterial blood and CSF) signal and comparable CNR(WM/GM) to conventional MP-RAGE images. The preliminary results showed that segmentation of grey matter could be significantly improved due to the blood suppression of DANTE pulse trains compared with conventional MP-RAGE brain structure images.

Zifei LIANG^1,2, Xiaohai HE¹, Andreia V. Faria², Kenishi Oishi², Yue Li³, Kinya Okada^2,4, Can Ceritoglu⁵, Xiaoying Tang⁵, Michael Miller⁵, and Susumu Mori^2,6
1College of Electronics and Information Engineering, Sichuan University, Chengdu, Sichuan, China, ²Johns Hopkins University School of Medicine, BALTIMORE, MD, United States, ³AnatomyWorks,LLC, BALTIMORE, MD, United States, ⁴MitsubishiTanabe Pharma Corporation, Kawagishi, Japan, ⁵Center for Imaging Science, Johns Hopkins University, BALTIMORE, MD, United States, ⁶Kennedy Krieger Institute, BALTIMORE, MD, United States

We tested the robustness of a multi-atlas whole-brain segmentation tool against different imaging protocols. We measured the volumes of 286 structures in 72 healthy brains from ADNI database, from three scanner manufacturers and two field strengths. The protocol impact, that explained 1.5% of the data variation, is far smaller than age effect, that explained 10.4% of the data variation, indicating that the data pooled from multiple sources can be used to evaluate biological effects. This type of robust technology is a key to apply quantitative analysis for clinical diagnosis, in which highly consistent image protocol cannot be expected.

Ana-Maria Oros-Peusquens¹, Johannes Lindemeyer¹, and N. Jon Shah^1
1Institute of Neuroscience and Medicine (INM-4), Research Centre Juelich, Juelich, Germany

We report on a multiparametric, high-resolution study of the visual cortex at 9.4T, including T1, q-space diffusion, HARDI, phase and T2* contrast and T1-T2 correlated relaxometry. The boundary between areas V1 and V2 is easily defined in most contrasts. Most interesting resuts include: featureless slow diffusion, higher amplitude of slow compared to fast diffusion in the internal lamina of the cortex and in white matter, layer-dependent mean displacement and probability of zero-displacement, visibility of at least 6 distinct layered regions in T1 maps, clear definition of V1/V2 border in M0, ‘layer’ visible in phase contrast which corresponds to fibre sheet of different orientation than generally radial one in the visual cortex.

Quentin Duché^1,2, Parnesh Raniga³, Gary F. Egan³, Oscar Acosta¹, Pierrick Bourgeat², Vincent Doré², Hervé Saint-Jalmes¹, and Olivier Salvado^2
1LTSI, INSERM, Université de Rennes 1, Rennes, France, ²CSIRO Digital productivity Flagship, Australian e-Health Research Centre, Herston, QLD, Australia,³Monash Biomedical Imaging, Monash University, VIC, Australia

Cortical thickness is a clinical biomarker of neurodegenerative diseases and ageing and is often included in clinical studies. Cortical thickness estimation (CTE) is commonly estimated using T1-weighted, MPRAGE sequence. The recent MP2RAGE sequence has been proposed with lower intensity inhomogeneity and increased tissue contrast. This abstract compares CTE with MPRAGE and MP2RAGE using a test-retest experiment. A bias between MPRAGE and MP2RAGE was found and could be corrected by a new partial volume model. MP2RAGE was found to be more reproducible than MPRAGE and should therefore be considered for measuring cortical thickness in clinical studies. MP2RAGE was found to be more reproducible than CTE with MPRAGE.

Omar Ocegueda¹, Eleftherios Garyfallidis², Maxime Descoteaux², and Mariano Rivera^1
1Computer Science Department, Centro de Investigación en Matemáticas, Guanajuato, Guanajuato, Mexico, ²Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science department, Université de Sherbrooke, Sherbrooke, Québec, Canada

We present a new algorithm for multi-modal symmetric diffeomorphic image registration and propose a validation protocol, based on existing manually annotated datasets, to quantitatively evaluate multi-modal image registration algorithms. Our validation protocol reveals that the Cross Correlation (CC) metric may be severely affected in the multi-modal case even though it has proven to be one of the most robust and accurate metrics for mono-modal registration. Our algorithm is based on the Symmetric Normalization (SyN) algorithm. It compares favourably with SyN with CC (in the multi-modal case) and is very competitive with SyN with Mutual Information.

Ek T Tan¹, Seung-Kyun Lee¹, Dominic Graziani¹, Matt A Bernstein², John Huston², Yunhong Shu², Paul T Weavers², Shengzhen Tao³, Joshua D Trzasko³, Jean-Baptiste Mathieu⁴, Christopher J Hardy¹, John F Schenck¹, and Thomas KF Foo^1
1GE Global Research, Niskayuna, NY, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States, ³Biomedical Engineering, Mayo Clinic, Rochester, MN, United States, ⁴GE Healthcare, Florence, SC, United States

A second iteration of a dedicated head-only gradient coil has been completed, allowing a slew rate of 700 T/m/s. Prior to imaging tests and in-vivo validation, we performed simulations to understand the extent of improvements to EPI at slew rates ranging from 200 T/m/s (attainable in many whole-body MRI scanners) to 700 T/m/s. We observe that the higher gradient slew rate will provide a greater than two-fold reduction in echo spacing, and also result in significant reduction in pixel distortion and increase in signal in the temporal lobes of the brain.

Mekala R. Raman¹, Yunhong Shu², Clifford R. Jack², and Kejal Kantarci^2
1Neurology, Mayo Clinic, Rochester, MN, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States

Our objective was to determine the effects of fixation on T1 relaxation of gray matter and white matter over time in ex vivo brain MRI. We found that T1 relaxation times of gray matter and white matter of fixed brain tissue attenuate over time, with rapid attenuation within the first 6 weeks of fixation and stabilization by 6 months.

Claudia Metzler-Baddeley¹, Sonya Foley², Karen Caeyenberghs³, and Derek K Jones^2
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²Cardiff University, Wales, United Kingdom, ³Gent University, Gent, Belgium

The mechanisms underlying brain plasticity remain unknown. We studied for the first time the effects of working memory training on plasticity in multiple MRI modalities of white matter microstructure. Demanding training led to increased axonal density and undemanding training to decreased axonal density in right parieto-frontal fibers. Training-induced cognitive improvements were related to increases in myelin water fraction. These results are the first demonstrations of opposing changes in measures of axonal density and myelin after varying training demands, suggesting that the intensity and nature of daily activities may critically shape an individual’s cognitive capacities and underpinning brain infrastructure.

Anisha Keshavan¹, Friedmann Paul², Mona Beyer³, Rohit Bakshi⁴, Phillip De Jager⁴, Massimo Filippi⁵, David Hafler⁶, Hanne Harbo³, Stephen Hauser¹, Ludwig Kappos⁷, Filippo Martinelli⁵, Daniel Pelletier⁶, Maria Rocca⁵, Till Sprenger⁷, William Stern¹, Bernard Uitdehaag⁸, Mike Wattjes⁸, Howard Weiner⁴, Jens Würfel², Alyssa Zhu¹, Jorge Oksenberg¹, and Roland Henry^1
1Neurology, UCSF, San Francisco, CA, United States, ²Charité Universitätsmedizin, Germany, ³Oslo University Hospital, Norway, ⁴Brigham and Women's Hospital, MA, United States, ⁵Scientific Institute Ospedale San Raffaele, Italy, ⁶Yale University, CT, United States, ⁷University Hospital, Basel, Switzerland,⁸Academic Hospital Vrije Universiteit, Netherlands

Acquiring data using non-standardized protocols could provide a cost and implementation efficient strategy for multisite MRI volumetric studies. We demonstrate feasibility and power considerations for such studies using a unique cohort of travelling controls across 8 institutions in the USA and Europe.

Peter T Fwu¹, Elysia P Davis², Claudia Buss², Muqing Lin¹, Kevin Head², Curt A Sandman², and Min-Ying Su^1
1Tu&Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, United States, ²Women and Children’s Health and Well-Being Project, Department of Psychiatry & Human Behavior, University of California, Irvine, CA, United States

Hippocampal volume and shape analysis was applied to 103 children (6-10 years old) to evaluate the association with their cognitive performance in different domains (learning, memory, recognition). Radial distance mapping and two non-rigid registration methods were applied to analyze shape based on the deformation matrix. Results obtained using these three different methods were consistent, and they suggest that different hippocampal regions are associated with different cognitive performance tasks. Analyses done separately in males and females showed similar results. None of the volumetric measurements revealed significant correlations, suggesting that shape analysis may provide a more sensitive tool for subregional analysis.

Zhe Zhang¹, Changcun Pan^2,3, Xiaodong Ma¹, Jie Tang³, Lihong Wang¹, Liwei Zhang^2,3, and Hua Guo^1
1Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, ²Department of Neurosurgery, Medical Center, Tsinghua University, Beijing, China, ³Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

: Visualizing human brainstem structures like nuclei and neural fibers is important to surgical planning for resection of brainstem lesions. This is challenging for conventional clinical MR sequences due to poor contrasts of nuclei with white matter and previous work reports findings at 7T. In this work, two 3D sequences were employed to visualize brainstem substructures in vivo at 3T. The visualization of brainstem structures like inferior olivary nucleus can be potentially significant for preoperative planning.

Marta Bianciardi¹, Nicola Toschi^1,2, Brian L. Edlow³, Cornelius Eichner¹, Kawin Setsompop¹, Jonathan R Polimeni¹, Emery N Brown⁴, Hannah C Kinney⁵, Bruce R Rosen¹, and Lawrence L Wald^1
1Department of Radiology, A.A. Martinos Center for Biomedical Imaging, MGH and Harvard Medical School, Boston, MA, United States, ²Medical Physics Section, Department of Biomedicine and Prevention, Faculty of Medicine, University of Rome “Tor Vergata”, Rome, Italy, ³Department of Neurology, A. A. Martinos Center for Biomedical Imaging, MGH & Harvard Medical School, Boston, MA, United States, ⁴Department of Anesthesia, Critical Care and Pain Medicine, MGH, Boston, MA, United States, ⁵Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States

Despite spectacular advances in neuroimaging of the human cerebral gray-matter, in-vivo visualization of human brainstem nuclei (Bn) is more challenging because of the limited sensitivity and contrast between Bn and adjacent white-matter using standard neuroimaging methods. Through combined examination of 1.1mm-isotropic multi-contrast (diffusion-fractional-anisotropy and T2-weighted) anatomical images acquired at 7 Tesla, we automatically generated in-vivo probabilistic brainstem labels of subcortical hubs of the ascending-arousal, autonomic and motor systems. These labels constitute a first step in the development of an in-vivo neuroimaging template of Bn in standard space to facilitate future clinical and research investigations of human brainstem function and pathology.

Birgit Renske Plantinga^1,2, Alard Roebroeck³, Matteo Bastiani³, Valentin Gereon Kemper³, Maartje Melse¹, Kâmil Uludag³, Mark Kuijf⁴, Ali Jahanshahi¹, Bart ter Haar Romenij², and Yasin Temel^1,5
1Department of Neuroscience, Maastricht University, Maastricht, Limburg, Netherlands, ²Biomedical Image Analysis, Eindhoven University of Technology, Eindhoven, Noord-Brabant, Netherlands, ³Department of Cognitive Neuroscience, Maastricht University, Maastricht, Limburg, Netherlands, ⁴Department of Neurology, Maastricht University Medical Center, Maastricht, Limburg, Netherlands, ⁵Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Limburg, Netherlands

Ultra-high field diffusion weighted ex vivo MRI was used to investigate the connectivity profile and parcellation of the human subthalamic nucleus (STN) at high resolution. The results show a more pronounced connection to the substantia nigra pars compacta than what is currently assumed. Furthermore, STN connections to the ascending internal capsule and the anterior part of the internal globus pallidus suggest that the posterior dorsal part of the STN is involved in motor and the anteromedial part is involved in limbic processes respectively. These findings may aid in improving the targeting in deep brain stimulation surgery of the STN.

Yosef Berlow¹, Mara Bahri¹, Laura McMahon¹, John Nutt², Susan Goelz³, Ted Yednock³, Wagner Zago³, Randall Woltjer⁴, C.Dirk Keene⁵, and William Rooney^1
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, United States, ²Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States, ³Prothena, CA, United States, ⁴Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States, ⁵Department of Pathology, University of Washington, Seattle, Washington, United States

Ultra-high field MRI was used to collect high spatial resolution MRI data from intact postmortem brainstems of healthy controls and individuals with Parkinson's disease.

Emma Biondetti¹, Jonathan D. Clayden², Alessandra Bertoldo³, Declan T. Chard⁴, and Claudia A. M. Wheeler-Kingshott^4
1UCL Department of Medical Physics and Biomedical Engineering, University College London, London, England, United Kingdom, ²Developmental Imaging and Biophysics Section, UCL Institute of Child Health, University College London, London, England, United Kingdom, ³Department of Information Engineering, University of Padova, Padova, Italy, ⁴NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom

In this work we investigate the reproducibility of a relevant connectivity pattern formed by different areas of the brain cortex. To identify this pattern, we use data of cortical thickness measured in healthy subjects, in correspondence of sixty-four automatically parcellated grey matter areas. We then apply a leave-one-out approach and, finally, resample the data set to evaluate the influence of single subject data over the final result. We conclude that this technique is reproducible with different data set and suggest it as a tool for studying cortico-cortical connectivity.

Deirdre M McGrath^1,2, Nishant Ravikumar¹, Alejandro F Frangi¹, Iain D Wilkinson², and Zeike A Taylor^1
1CISTIB, Center for Computational Imaging & Simulation Technologies in Biomedicine, University of Sheffield, Sheffield, South Yorkshire, United Kingdom,²Academic Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom

Magnetic resonance elastography (MRE) of the brain is currently being evaluated as a biomarker of neurodegenerative disease. However, MRE-measured biomechanical data for healthy brain varies widely. Therefore, it is important to assess the possible impact of other factors such as variable brain geometry and cranial anatomy. Finite element model simulations of MRE are carried out on brain meshes including the falx cerebri and tentorium cerebelli membranes to examine the role these structures play in wave transmission and reflection and how they may influence the MRE-measured displacement fields and inversion reconstructions of brain biomechanics.

Holly Elizabeth Holmes*¹, Rajiv Ramasawmy¹, Da Ma^1,2, Nicholas Powell^1,2, Manuel Jorge Cardoso², Marc Modat², Simon Walker-Samuel¹, Sebastian Ourselin², Bernard Siow+^1,2, and Mark Lythgoe+^1
1Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom, ²Centre for Medical Image Computing, University College London, London, Greater London, United Kingdom

The feasibility of low-field (1T) MRI for high throughput morphological phenotyping of transgenic mice is discussed, in comparison to high-field (9.4T) MRI.

Allen Q. Ye¹, Olusola Ajilore², Alessandro Febretti³, Andrew Johnson³, Johnson GadElkarim², Shaolin Yang², Richard Magin¹, Anand Kumar², and Alex D. Leow^2
1Dept. of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ²Dept. of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ³Dept. of Computer Science, University of Illinois at Chicago, Chicago, IL, United States

This abstract presents the utility of using dimensionality reduction to visualize lobectomies in a virtual reality environment. Exploration of a Monte Carlo simulation of lobectomies, along with targeted “rich club” removal was performed and displayed using the Omegalib framework. Results show a significant increase in overall distance for the dimensionality reduced embedding for the targeted versus random removal. Qualitative results also show a stark change between random removals and targeted removal.

Christine Lucas Tardif¹, Christopher John Steele¹, Pierre-Louis Bazin¹, Arno Villringer¹, and Claudine Joëlle Gauthier^1,2
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Saxony, Germany, ²Department of Physics, Concordia University, Montreal, Quebec, Canada

T1 maps were acquired under normal, hypercapnic (increased CO2) and hyperoxic (increased O2) breathing conditions to investigate the confounding effects of dissolved oxygen, blood flow and blood volume on computational anatomy studies. We show a decrease in T1 during hypercapnia and hyperoxia, as well as an increase in cortical thickness during hypercapnia. These biases should be taken into account when interpreting MR-based structural plasticity studies of ageing and learning, for instance.

J.H.G. Helthuis¹, A.A. Harteveld², J. Hendrikse², R.L.A.W. Bleys³, and J.J.M. Zwanenburg^2,4
1Department of Neurosurgery, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ³Department of Anatomy, University Medical Center Utrecht, Utrecht, Netherlands, ⁴Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

One of the challenges in blood flow modeling is determining boundary conditions such as peripheral resistance. More detailed knowledge regarding the morphology of the cerebral arterial tree could help in setting correct boundary conditions. Therefore, in this study a novel approach of scanning cerebral arterial casts with 7 tesla MRI was explored for gaining more detailed insight in the morphological features of the cerebral arterial network. The results show that ultrahigh-resolution MRI enables accurate measurement of the human cerebral vascular casts. In the future, we want to apply this technique for accurate modeling of the cerebral arterial vasculature.

Makoto Obara¹, Osamu Togao², Masami Yoneyama¹, Tomoyuki Okuaki³, Shuhei Shibukawa⁴, and Marc Van Cauteren^3
1Philips Electronics Japan, Minato-ku, Tokyo, Japan, ²Department of Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan,³Philips Healthcare, Tokyo, Japan, ⁴Department of Radiology, Tokai University Hospital, Kanagawa, Japan

Intracranial MR angiography using acceleration-selective arterial spin labelling (AccASL) was implemented and images acquired in five healthy volunteers and the peripheral vessel visualization in the middle cerebral artery (MCA) area were compared with time-of-flight (TOF) approach. We show that AccASL can visualize peripheral arterial both selectively (without venous signal) and with better efficiency compared to the TOF approach.

Addiction, Drug Exposure, Pain, Sleep

Tuesday 2 June 2015

Hyeon-Man Baek^1,2, Mirim Bang¹, Youngjae Jeon¹, and Jooyun Kim^1
1Center for MR Research, Korea Basic Science Institute, Ochang, Chungbuk, Korea, ²Department of Bio-Analytical Science, Univerity of Science & Technology, Daejeon, Chungnam, Korea

We applied quantitative DTI to investigate the association between alcohol use and white matter integrity in adults. The purpose of this study was to examine the reproducibility of the DTI by evaluating measures of anisotropy and diffusivity in brain regions such as the fornix, cingulum, and the corpus callosum. In the FA map of alcoholic, the white matter in the area of cingulum and corpus callosum shows a decrease in fractional anisotropy.

Hyeon-Man Baek^1,2, Siekyeong Kim³, Jeonghwan Lee³, Youngjae Jeon¹, Jooyun Kim¹, and Mirim Bang^1
1Center for MR Research, Korea Basic Science Institute, Ochang, Chungbuk, Korea, ²University of Science & Technology, Daejeon, Korea, ³Department of Psychiatry, Chungbuk National University, Cheongju, Chungbuk, Korea

In this study, we performed in vivo short-echo time (TE) 1H-MRS to investigate brain metabolite levels in the left DLPFC of alcohol-dependent patients and healthy controls. For quantitative spectral analysis, metabolite basis sets were acquired in-house on the same 3T MRI scanner. Significantly decreased tCho and Ins concentrations were found in the DLPFC of the alcoholics as compared to the controls (p=0.001, p=0.008, in Figure 2). In addition, there was a trend towards increasing Gln in alcoholic dependents (p=0.059). These metabolic abnormalities may be neurochemical correlate of an increased risk to develop alcoholism.

Fuchun Lin¹, Yasong Du², Yan Zhou³, Jianrong Xu³, 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, ²Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, China, ³RenJi Hospital, Jiao Tong University Medical School, Shanghai, China

Resting-state functional connectivity (rsFC) was used to investigate six bilateral striatal functional networks in adolescent students with Internet addiction disorder (IAD). These functional networks involve multiple cortical and subcortical regions that are known to engage in affective and motivation processing, and cognitive control. Although both the IAD subjects and controls show similar FC patterns for six bilateral striatal subregions, however, IAD had altered connectivity strength for every striatal subregion. Moreover, the strengthes of rsFC between rVSs and dorsal ACC, between lDC and dorsal/rostral ACC, between lVRP and right IFG, were negatively correlated with SCARED, and the strength of rsFC between rVSs and dorsal caudate was negatively correlated with YIAS. Our findings suggest that IAD is associated with alterations of corticostriatal functional circuits and rsFC may be used as a qualified biomarker to understand the underlying neural mechanisms or to evaluate the effectiveness of specific early interventions in IAD.

wei li¹, yarong wang¹, qiang li¹, jianjun ye¹, and wei wang^1
1Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi¡¯an, Shaanxi, China

DTI was used to assess whether white matter integrity measured at the baseline differ between patients who subsequent abstinence and those who resumed to heroin use. The results shown that future relapsers had lower white matter integrity compared with subsequent abstinence, and the white matter integrity in left posterior limb of the internal capsule correlated negatively with the heroin positive urinalysis rate. Thus the white matter integrity might be of prognostic value and added to the neurobiological relapse risk profile of heroin abuse. This findings may suggest that strategies for improving white matter integrity may developing a new interventions for the reduction of relapse in heroin addiction.

Deepika Bagga¹, Namita Singh¹, Shilpi modi¹, Prabhjot Kaur¹, Subash Khushu¹, Debajyoti Bhattacharya², and Mohan lal Garg^3
1INMAS, Delhi, Delhi, India, ²Base Hospital, Delhi, India, ³Panjab University, Chandigarh, India

MRI findings suggest structural, functional and metabolic alterations in chronic alcoholics. However, very few studies specifically sought to examine the alterations in associated hemodynamic or paramagnetic properties (as reflected by T2 relaxation times (T2-RT)) in this population. Thus, we carried out a T2 relaxometry study on alcohol dependents and control subjects .Alcohol dependent subjects showed increased T2 relaxation times in different brain regions suggestive of tissue disruption in these individuals which could, in part, be responsible for impaired cognitive abilities.

Prantik Kundu¹ and Valerie Voon^2
1Depts. of Radiology and Psychiatry, Icahn School of Medicine at Mt. Sinai, New York, NY, United States, ²Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom

Study of functional connectivity differences between current smokers and non-smokers demonstrates highly significant increases in cortico-cortical and cortical-subocritcal connectivity of prefrontal and frontal areas associated with nicotine-stimulated cholinergic pathways. Importantly, connectivity differences were elucidated based on multi-echo fMRI, for which seed-based functional connectivity is robust to motion artifact and associated type I errors in group comparisons.

Rafael O'Halloran¹, Nelly Alia-Klein², and Rita Z Goldstein^2
1Radiology, Icahn School of Medicine at Mt Sinai, New York, NY, United States, ²Psychiatry, Icahn School of Medicine at Mt Sinai, NY, United States

Previously reported white matter changes associated with cocaine use disorder (CUD) have been limited to focal areas of fractional anisotropy (FA) reduction in several areas including the corpus callosum, internal capsule, and cingulum. In this study, group FA and connectivity differences were assessed using a state-of-the-art dMRI protocol. Results indicate a more widespread reduction of FA in subjects with cocaine use disorder compared to age-matched controls, corroborating previous findings but also expanding the territory of white matter integrity changes implicated in the disease. Furthermore, connectivity analysis based on tractography showed that CUD subjects had lower connectivity than controls in several networks, the most significant of which was the right side network of the hippocampus, amygdala, posterior orbito-frontal cortex, and gyrus rectus.

Jianjun Ye¹, Wei Wang¹, Wei Li¹, Dongsheng Zhang¹, and Dandan Zheng^2
1Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, xi'an, shaanxi, China, ²MR Advanced Application and Research Center, GE Healthcare China, Beijing, Beijing, China

Researchers interested in the effect of methadone maintenance treatment on heroin craving

Do-Wan Lee^1,2 and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul, Korea, ²Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea

The first goal of this study was to determine the influence of dose-dependent short-term binge ethanol (SBE) exposure on cerebral neurochemical differences and responses among controls (CNTL) and low-(SBE-1.5) and high-(SBE-2.5) dose ethanol-exposed rats. The second goal was to determine correlations between metabolite-metabolite levels (pairs-of-metabolite-levels) using individual metabolite data from hippocampal region of SBE-exposed rats. From our results and previous studies, altered various metabolite signals may indicate that SBE-exposure leads to various biological changes, such as changes in rate of GABA and glucose synthesis, impairment of an antioxidant defense system, abnormal ATP function in energy-metabolism, and dysfunctions of anaerobic respiration.

Daniel Coman¹, Basavaraju G Sanganahalli¹, Lihong Jiang¹, Fahmeed Hyder^1,2, and Kevin Behar^3
1Diagnostic Radiology, Yale University, New Haven, Connecticut, United States, ²Biomedical Engineering, Yale University, New Haven, Connecticut, United States, ³Psychiatry, Yale University, New Haven, Connecticut, United States

MDMA use results in extreme hyperthermia. Neuroimaging of brain temperature could provide mechanistic insights of MDMA action. We measured spatial distributions of MDMA-induced temperature changes and dynamics in rat cortex using BIRDS with TmDOTMA^4-. MDMA induced a fast and homogenous temperature rise throughout the cortex. The correlation between the cortical and body temperature changes suggest that the heat produced in the body is carried by blood to the brain and contributes partially to cortical temperature increase. MDMA-induced changes in temperature, blood flow, and neuronal activity suggest a lack of neurovascular coupling in the thalamus compared to the cortex.

Van Nguyen¹, Suyinn Chong², Karine Mardon¹, Quang Tieng¹, Graham Galloway¹, and Nyoman Kurniawan^1
1Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia, ²Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia

This study aims at monitoring abnormal brain development longitudinally in the offspring under maternal alcohol consumption using mouse models of Fetal Alcohol Spectrum Disorders (FASD). In-vivo volumetric MRI and Tensor-based Morphometry are used to make comparisons between FASD and control brains at adolescence and adulthood. Ex-vivo Computed Tomography is used to monitor skull development. Correlations between brain and skull abnormalities are made. This study found that in-utero alcohol exposure at moderate dose may cause subtle but observable brain malformations in the offspring that can be detected at early age and persist into adulthood.

Xiaojie Wang¹, Sarah Plat¹, Molly McGinnis¹, Kathleen A Grant¹, and Christopher D Kroenke^1
1Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States

Adult Male and female rhesus monkeys underwent 6 months of voluntary ethanol drinking following a standard protocol. DTI measurements were performed prior to ethanol exposure and following 6 months of alcohol self-administration. To determine whether white matter microstructure changes due to voluntary alcohol drinking, a voxel-wise t-test was performed on white matter fractional anisotropy (FA) at 6 months and baseline using tract-based spatial statistics. Significant FA reductions were detected in frontal white matter tracts. These results indicate that the progression of ethanol-induced brain damage observed in this animal model is consistent with observations made in studies of human alcoholics.

Dan Madularu¹, Jason R. Yee², William M. Kenkel², Kelsey A. Moore², Praveen Kulkarni², Waqqas M. Shams¹, Craig F. Ferris², and Wayne G. Brake^1
1Concordia University, Montreal, QC, Canada, ²Northeastern University, Boston, MA, United States

Previous studies demonstrate that schizophrenia symptomatology in women is dependent upon estrogen levels. Estrogen has beneficial properties when administered in conjunction with antipsychotics, and estrogen also alters dopamine neurotransmission in rats; suggesting a possible interaction between the two. The aim of the current study was to investigate this possible interaction using functional magnetic resonance imaging in awake, female rats. Amphetamine-sensitized, ovariectomized rats receiving no, low, or high levels of estradiol replacement were used, and changes in blood-oxygen-level-dependent (BOLD) signal were recorded over time in response to an acute amphetamine injection. Increasing levels of estradiol enhanced BOLD activation in pathways previously known to be implicated in schizophrenia symptomatology, such as the mesocorticolimbic, habenular and olfactory pathways as well as more widespread areas. We propose here the first comprehensive “amphetamine activation map” integrating brain regions where dopaminergic transmission is influenced by estrogen levels.

Hanyue Wang^1,2, Yarong Wang¹, Qiang Li³, Dongsheng Zhang³, Lina Wang³, Jia Zhu³, Wei Li³, Chongjun Zhang⁴, Jiajie Chen³, and Wei Wang^3
1Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi¡¯an, Shan Xi, China, ²Clinic, Air Force Equipment Academy, Beijing, Beijing, China,³Radiology, Tangdu Hospital, the Fourth Military Medical University, Shan Xi, China, ⁴Clinic, Air Force Equipment Academy, Beijing, China

We used functional magnetic resonance imaging(MMT) to investigate the neural basis of the length effects of long-term methadone maintenance treatment on brain response to heroin-related cues in former heroin-dependent individuals. Fifteen patients (duration of MMT ¡Ü 1 year, group A) , fifteen matched patients (duration of MMT 2-3 years, group B) and 17 healthy controls were included. The self-reported heroin craving score demonstrated no significant difference between Group A and B. Compared with Group B, Group A demonstrated greater activation in caudate when exposed to drug-related cue. Long-term MMT may improve the brain craving response by regulating the impaired function of caudate.

Chien-Yuan Eddy Lin^1,2, I-Hsiao Yang^3,4, Hsiu-Ling Chen^3,4, Meng-Chang Tsai⁵, Pei-Chin Chen^3,4, Meng-Hsiang Chen^3,4, and Wei-Che Lin^3,4
1GE Healthcare, Taipei, Taiwan, ²GE Healthcare China, Beijing, China, ³Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ⁴Chang Gung University College of Medicine, Kaohsiung, Taiwan, ⁵Department of psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Alteration of cerebral blood flow (CBF) in heroin users under methadone maintenance treatment (MMT) had been reported but the acute effect before and after methadone administration is still less known. The purpose of this study is to investigate the acute changes of CBF in MMT subjects one hour before and after methadone administration by using arterial spin labeling perfusion MRI, and their relationships with history of heroin usage and methadone treatment.

Bing Ji^1,2, Zhihao Li^1,3, Claire Coles⁴, Julie A Kable⁴, Renjie Zhang², and Xiaoping Hu^1
1Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA, United States, ²School of Optical Electrical and Computer Engineering, University of Shanghai for Science & Technology, Shanghai, Shanghai, China, ³Institute of affective and Social Neuroscience, Shenzhen University, Shenzhen, Guangdong, China, ⁴Psychiatry and behavioral Science, Emory University, Atlanta, GA, United States

Prenatal alcohol exposure (PAE) is associated with a wide range of cognitive and behavioral deficits. Previous neuroimaging studies of PAE only focused on a few brain regions or neural pathways despite evidences that the teratogenic impact is widespread. The present study examined PAE associated alterations of functional connectivity in 7 brain networks and significant reduction of functional connectivity was observed in 6 of them. The current results support the general hypothesis of PAE associated large-scale network-dysconnectivity thus motivating whole brain connectivity based profiling.

Zhihao Li^1,2, Claire Coles³, Mary Ellen Lynch³, and Xiaoping Hu^1
1Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA, United States, ²Institute of Affective and Social Neuroscience, Shenzhen University, Shenzhen, Guangdong, China, ³Psychiatry and Behavioral Science, Emory University, Atlanta, GA, United States

The present resting-state fMRI study examined the developmental effect of prenatal cocaine exposure (PCE) on functional connectivity in brain networks associated with amygdala (emotion) and left dorsal lateral prefrontal cortex (cognitive functions). The data reflected an improved capacity for stress coping and network segregation in typical development, but this improvement is compromised by PCE. The present results provide further and direct evidence supporting the view of PCE associated long-term effect on arousal regulation.

Scott Peltier¹, Eric Ichesco², and Richard Harris^2
1Functional MRI Laboratory, University of Michigan, Ann Arbor, MI, United States, ²Anesthesiology, University of Michigan, Ann Arbor, MI, United States

Multivariate pattern classfication was applied to a drug study of fibromyalgia patients, and was able to distinguish placebo from drug with high accuracy.

Baohui Lou^1,2, Min Chen^1,2, and Xiaojie Luo^3
1Graduate School of Peking Union Medical College, Beijing, Beijing, China, ²Beijing Institute of Geriatrics, Beijing Hospital, Beijing, Beijing, China, ³Department of Radiology, Beijing Hospital, Beijing, Beijing, China

This study focused on the rs12970134 near melanocortin 4 receptor (MC4R) gene related structural and functional alteration of brain in young obese adults from Chinese HAN population. Voxel-based morphometry analysis of T1-weighted MRI and functional connectivity (FC) analysis of resting-state fMRI were adopted. Increased FC strength between the bilateral hypothalamus and the regions of food reward and default mode network were demonstrated in MC4R A-allele carriers in the young obese adults.

Anna E Mechling^1,2, Tanzil Arefin^1,3, Hsu-Lei Lee¹, Thomas Bienert¹, Marco Reisert¹, Sami Ben Hamida⁴, Jürgen Hennig¹, Dominik v. Elverfeldt¹, Brigitte Kieffer⁵, and Laura-Adela Harsan^1
1Medical Physics, University Medical Center Freiburg, Freiburg, B-W, Germany, ²Faculty of Biology, University of Freiburg, Freiburg, B-W, Germany, ³Bernstein Center for Computational Neuroscience, University of Freiburg, Freiburg, B-W, Germany, ⁴Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden, Alsace, France, ⁵Douglas Research Centre, Montreal, Quebec, Canada

We investigate functional and structural brain connectivity changes non-invasively via resting-state functional MRI using BOLD and diffusion weighted MRI respectively in mu-opioid receptor (MOR) knock-out mice compared to controls. Our study provides for the first time a clear link between disrupted MOR function and whole brain “connectome” alterations. Remarkable are the observed remodeling features of networks involving brain areas that control reward and pain processing. Our findings reproduce known functions of MOR but also point towards novel involvement pathways of the receptor interesting for potential therapeutic compounds for possible use in psychiatric patients in the future.

Do-Wan Lee^1,2, Chul-Woong Woo², Sang-Tae Kim², Choong Gon Choi³, Bo-Young Choe¹, and Dong-Cheol Woo^2
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul, Korea, ²Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul, Korea, ³Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

This study aimed to quantitatively assess the neurobiological changes and responses, after stress-induced sleep disturbance in rats using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 9.4-T. Glu concentrations were significantly lower in hippocampal region of stress-induced-sleep-perturbed rats than in controls (***p=0.004). From our results and previous studies, significantly lower Glu concentrations might reflect an alteration in glutamate turnover in SSP, in comparison to controls, due to excessive glutamatergic neurotransmission driven by neuronal hyperactivity. We determined that significantly lower Glu signals in hippocampus result from stress-induced sleep perturbation, which provides insights into neurochemical alterations and responses associated with psychiatric disorders.

Xi-Jian Dai^1,2, Hong-Han Gong², De-Chang Peng², Li Pei², and Yi-Xiang Wang^1
1Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, ²Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

Despite wide prevalence and broad medical impact, limited work has been done to investigate neurobiological mechanisms underlying within a neuroscientific framework, and still too many disputes left unclear. In this study, we demonstrated that chronic primary insomnia does not appear to be associated with substantial regional spontaneous activity deficits, and the inability to fall asleep may be related to a arousal mechanisms to increased activity in temporal cortex and the interacting neural networks in the neurobiology of insomnia, including an emotion-regulating system, a cognitive system and a visual system. Such changes may decrease arousal thresholds and/or increase perceptions of wakefulness.

Ece Ercan¹, Carson Ingo¹, Cesar Magro Checa², Mark van Buchem³, Andrew Webb¹, and Itamar Ronen^1
1C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ³Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Systemic lupus erythematous (SLE) is an autoimmune disease affecting multi-organ systems. SLE adversely impacts the central nervous system, causing neurological and psychiatric (NP) symptoms in 40% of the patients. Heterogeneity of NP symptoms among patients and the lack of gold standard make diagnosis of Neuropsychiatric SLE (NPSLE) challenging. In this study we applied a multi-modal approach to better characterize white matter microstructural damage in NPSLE. Our results suggest that only a multimodal approach has the potential to thoroughly identify disease-related changes in the brain due to complex disease mechanisms such as NPSLE and thus to improve the clinical diagnosis.

Psychosis

Tuesday 2 June 2015

Zhongxu An¹, Sandeep Ganji¹, Katherine Borner¹, Ana Stan², Subroto Ghose², Carol Tamminga², and Changho Choi^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, United States

We report 1H MRS measurement of brain metabolites in anterior cingulated cortex in schizophrenia patients versus healthy subjects. 34 schizophrenia patients and 22 age-matched normal subjects were enrolled in the study. Using previously reported PRESS echo times at 7T, the signals of GABA, glutamate, and Glycine were completely resolved from neighboring resonances. Group analysis indicated significant reduction in glutamate (p<0.007) and significant increase in glycine (p<0.04) in schizophrenia. Data showed a trend of reduced GABA in schizophrenia (p<0.2).

Fei Du¹, Cagri Yuksel¹, Scott Lukas¹, Bruce Cohen¹, and Dost Ongur^1
1McLean Hospital, Harvard Medical School, Belmont, MA, United States

In vivo probes of cerebral bioenergetics have the capacity to provide crucial information to characterize the exact abnormalities and delineate their relationships with pathophysiology and symptom presentation of schizophrenia. Using novel 31P-MT-MRS and both 1st-episode and chronic patients, our findings indicate schizophrenia may be characterized by an initial active phase of excessive glutamatergic neurotransmission and bioenergetic activity, which then progressively becomes downregulated and result in decreased intracellular pH in the chronic condition. Our findings provide insight into the progression of schizophrenia and highlight the value of using cerebral activity and bioenergetic metabolism as new biomarkers of the pathophysiology of schizophrenia.

Huaiqiang Sun¹, Su Lui¹, Haoyang Xing¹, Xiaoqi Huang¹, and Qiyong Gong^1
1Huaxi MR Research Center, West China Hospital of Sichuan University, Chengdu, China

Three shape patterns of subcortical structures in medication-naïve first-episode schizophrenia patients was identified according to the deformation parameters between patient individuals and the atlas constructed from matched healthy controls. Patients belong to different patterns did not differ in demographic features but in clinical symptoms. The shape pattern revealed in this study may reflect distinct underlying pathology.

Gen Kaneko¹, Daniel Coman¹, Basavaraju G Sanganahalli¹, Helen Wang¹, Peter Herman¹, Lihong Jiang¹, Jyotsna Rao¹, Stephanie M Groman², Jane R Taylor², Robin A de Graaf¹, and Fahmeed Hyder^1,3
1Department of Diagnostic Radiology, Yale University, New Haven, CT, United States, ²Department of Psychiatry, Yale University, New Haven, CT, United States, ³Department of Biomedical Engineering, Yale University, New Haven, CT, United States

Visual hallucination is a core positive symptom in schizophrenia associated with increased functional connectivity between visual and hippocampal areas observed by fMRI. We investigated anatomical and metabolic changes in a rat model of schizophrenia (MAM-E17). Compared to controls, MAM rats had thinner visual cortex and higher corpus callosum fractional anisotropy in posterior, but not anterior, regions. In MAM rats neuronal energy metabolism and glutamate-glutamine cycling were both higher in visual cortex, but unchanged in somatosensory cortex. These results suggest that gray/white matter changes and enhanced metabolic activity in the visual pathway may underlie schizophrenic symptoms of visual hallucination.

Su Xu^1,2, Rao P Gullapalli^1,2, and Douglas O Frost^3,4
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States, ²Core for Translational Research in Imaging @ Maryland, University of Maryland School of Medicine, Baltimore, Maryland, United States, ³Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, United States, ⁴Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, United States

Olanzapine is a widely prescribed atypical antipsychotic drug (AAPDs) to treat a variety of psychiatric disorders. However, little is known about the long-term effects of olanzapine treatment before the brain is fully developed. Here, we use in vivo proton MRS to demonstrate long-term reductions in the levels of both glutamate and -aminobutyric acid in the nucleus accumbens of adult rats treated with olanzapine during adolescence. The finding is an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients.

Mariana Lazar¹, Fernando Boada¹, Laura Miles¹, Dolores Malaspina¹, and Oded Gonen^1
1New York University, New York, New York, United States

In this study we evaluated the gray matter microstructural integrity in schizophrenia using mean kurtosis (MK), a metric of microstructural complexity, obtained using diffusional kurtosis imaging. Seventeen chronic schizophrenia patients and eighteen healthy control participants 30 to 55 years old participated in the study. Increased MK was observed in patients in extended temporal and some prefrontal cortical regions. These findings suggest MK as a promising biomarker of altered gray matter microstructure in schizophrenia. Increased cortical MK was found to associate with inflammatory processes such as astrogliosis. Thus, these findings may bring additional evidence to ongoing inflammation hypotheses in schizophrenia.

Alberto Corcoba^1,2, Sandra Giovanoli³, Mirko Schnider², Kim Q. Do², Rolf Gruetter^1,4, Urs Meyer³, and Joao M.N. Duarte^1
1LIFMET, EPFL, Lausanne, Vaud, Switzerland, ²Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Vaud, Switzerland, ³Physiology and Behavior Laboratory, Swiss Federal Institute of Technology Zurich, Zurich, Zurich, Switzerland, ⁴Radiology, UNIL and UNIGE, Lausanne and Geneva, Vaud and Geneva, Switzerland

Multiple environmental risk factors, including prenatal maternal infection and peri-pubertal psychological stress, potentiate emergency of schizophrenia and susceptibility for psychopathology. We now demonstrate that the combination of peri-pubertal stress after asymptomatic maternal infection leads to development of neurochemical alterations in the mouse cortex but not hippocampus.

Jun Hua^1,2, SeungWook Lee³, Nicholas I.S. Blair³, Allison Brandt⁴, Jaymin Patel³, Andreia V. Faria¹, Issel Anne L. Lim^1,2, James J. Pekar^1,2, Peter C. M. van Zijl^1,2, Christopher A. Ross^4,5, and Russell L. Margolis^4,5
1Neurosection, Div. of MRI Research, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ³Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States, ⁴Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ⁵Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Neurovascular alterations have been implicated in the pathophysiology of schizophrenia. As arterioles are most responsive to metabolic changes, arteriolar cerebral blood volume (CBVa) is an important indicator of cerebrovascular regulation. We show that grey matter (GM) CBVa, measured with the inflow-based vascular-space-occupancy (iVASO) MRI technique, is significantly reduced in schizophrenia patients. The GM CBVa changes were found in multiple areas across the whole brain, with the most significant changes in the frontal and parietal regions. Our results imply that neurovascular abnormality may play a role in schizophrenia, and suggest CBVa as a potential surrogate marker for the disease.

Jun Hua^1,2, Nicholas I.S. Blair³, Ann Choe^1,2, Anita Barber^4,5, Allison Brandt⁶, Issel Anne L. Lim^1,2, Feng Xu^1,2, James J. Pekar^1,2, Peter C. M. van Zijl^1,2, Christopher A. Ross^4,6, and Russell L. Margolis^4,6
1Neurosection, Div. of MRI Research, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ³Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States, ⁴Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States,⁵Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, United States, ⁶Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

The thalamus is a small brain structure that relays neuronal signals between subcortical and cortical regions. Abnormal thalamocortical connectivity in schizophrenia has been documented in previous studies, which used the entire thalamus as a single node. Anatomically, the thalamus is subdivided into multiple distinct nuclei with different connections to various cortical regions. With the enhanced sensitivity of BOLD fMRI at 7T, sub-regions in the thalamus defined by a diffusion based atlas were employed as separate seeds to calculate whole-brain functional connectivity. Our results demonstrate widespread changes in thalamocortical functional connectivity across multiple brain regions in schizophrenia.

Li Yao¹, Wei Deng², Wenjing Zhang¹, Yuan Xiao¹, Fei Li¹, Jieke Liu¹, John A Sweeney³, Qiyong Gong¹, and Su Lui^1
1Huaxi MR Research Center, Chengdu, Sichuan, China, ²Department of Psychiatry, Stat Key Lab of Biotherapy, West China Hospital of Sichuan University, Sichuan, China, ³UT Southwestern Medical Center, Texas, United States

Using graph theory-based approaches,we explored whether there are different age-related brain functional change patterns in chronic but never treated schizophrenia patients than healthy controls. Our findings revealed altered global topological organization toward regularization and decreased nodal centralities in amygdala, olfactory, precuneus and putamen in later phase of schizophrenia without the potential confounding of antipsychotic treatment. Specifically, the age-related disruptions in amygdala suggested this region might act as an important component in the physiopathologic evolution of long-term schizophrenia.

Orla M Doyle¹, Brandon Whitcher^2,3, Steven C.R. Williams¹, Mitul A Mehta¹, and Stephen M Lawrie^4
1Dept of Neuroimaging, IoPPN, King's College London, London, United Kingdom, ²Clinical & Translational Imaging, Pfizer, Cambridge, MA, United States, ³Dept of Mathematics, Imperial College London, London, United Kingdom, ⁴Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom

This is the first time that structural brain data, rCBF and MRS data have been jointly assessed for discriminating schizophrenia from controls. Twenty-four patients diagnosed with schizophrenia and 24 age- and gender-matched controls were included. An increase in discriminative power was not observed on combining modalities. rCBF was the most highly weighted modality. Predictive probabilities (the probability of belonging to the SCZ group) were not correlated with the level of antipsychotic medication. These results imply that perfusion imaging is a highly sensitive marker for schizophrenia. Future work should assess the specificity via differential diagnosis of psychiatric disorders.

Hsu-Hwa Tseng^1,2, Su-Chun Huang², Chih-Min Liu³, Tzung-Jeng Hwang³, Hai-Gwo Hwu³, Yung-Chin Hsu², Yu-Chun Lo², Yu-Jen Chen², and Wen-Yih Isaac Tseng^2
1School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ²Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

DISC1 gene influences the severity of the clinical symptoms of individuals with SZ. Higher PANSS scores in some specific subscales could be predicted in individuals with risk forms. Besides, DISC1 gene influences the white matter properties of thalamic radiation. Since all the subjects were medicated, we speculate that the negative correlations between the symptoms and the white matter properties might reflect in part the treatment effects. Individuals with the protective form of DISC1-27 seem to have a better treatment effect on negative symptoms.

Su-Chun Huang¹, Chih-Min Liu², Tzung-Jeng Hwang², Hai-Gwo Hwu², Yung-Chin Hsu¹, Yu-Chun Lo¹, Yu-Jen Chen¹, and Wen-Yih Isaac Tseng^1,3
1Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan, ²Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, ³Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

In the present study we found that after 4 weeks of treatment, GFA value was significantly increased in left SLF II, SLF III, and ML. The increase was not presented along the whole tract, but limited to discrete segments. Since all the patients reported reduced severity of symptoms after treatments, these results suggest that the medication can modulate the integrity of white matter tract, and further influence the clinical symptoms. Notably, all the differences were found in tracts related of sensory input and integration, implying that the core pathology of schizophrenia may be related to sensory integration

Yuan Xiao¹, Wei Deng², Huaiqiang Sun¹, Wenjing Zhang¹, Li Yao¹, Jia Liu¹, Min Wu¹, Chandan Shah¹, Qiyong Gong¹, and Su Lui^1
1Department of Radiology, West China Hospital of Sichuan University, Huaxi Magnetic Resonance Research Ctr., Chengdu, Sichuan, China, ²Department of Psychiatry, State Key Laboratory of Biotherapy, Chengdu, Sichuan, China

Tract-based spatial statistics was employed to investigate the white matter microstructure alteration in a rare case of chronic but never-medicated schizophrenia patients. 26 patients and 28 healthy controls were recruited in this study. It revealed widespread decrease of FA in the patients, especially in anterior thalamic radiation, corticospinal tract, cingulum (cingulate gyrus), forceps minor, inferior fronto-occipital fasciculus and superior longitudinal fasciculus. However, only forceps minor exhibited faster aging effect than controls suggesting the critical role of forceps minor in the progressive mechanism of schizophrenia.

Eric Plitman^1,2, Camilo de la Fuente-Sandoval³, Pablo León-Ortiz³, Francisco Reyes-Madrigal³, Gladys Gómez-Cruz³, Shinichiro Nakajima^1,4, Philip Gerretsen^1,5, M Mallar Chakravarty^6,7, Sofia Chavez^1,5, Jun Ku Chung^1,2, Fernando Caravaggio^1,2, Yusuke Iwata^1,4, Danielle Uy¹, Gary Remington^1,5, and Ariel Graff-Guerrero^1,5
1Centre for Addiction and Mental Health, Toronto, Ontario, Canada, ²Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, ³Instituto Nacional de Neurología y Neurocirugía, Mexico, ⁴Neuropsychiatry, Keio University School of Medicine, Japan, ⁵Psychiatry, University of Toronto, Toronto, Ontario, Canada, ⁶Douglas Mental Health University Institute, Montreal, Quebec, Canada, ⁷Psychiatry, McGill University, Montreal, Quebec, Canada

The degree to which myo-inositol (mI) and choline compounds (Cho) are disrupted in patients with schizophrenia is unclear. Proton magnetic resonance spectroscopy was used to compare mI and Cho levels in the associative striatum between antipsychotic-naïve patients experiencing their first non-affective psychosis episode and a matched group of healthy controls. Patients’ clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). mI and Cho were elevated in the patient group. mI was associated with PANSS Positive total, P3 (Hallucinatory Behaviour), and P5 (Grandiosity) scores. The concomitant elevation of mI and Cho supports early glial cell disruption in schizophrenia.

Aziz M Ulug^1,2, Mehmed Ozkan², Peter B Kingsley³, Ivana De Lucia¹, Azim Celik⁴, Pamela DeRosse^5,6, Anil Malhotra^5,6, and Philip R Szeszko^5,6
1Center for Neurosciences, Feinstein Institute for Medical Research, Manhasset, New York, United States, ²Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey, ³North Shore University Hospital, Manhasset, New York, United States, ⁴GE Healthcare, Antalya, Turkey, ⁵Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, United States, ⁶Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, New York, United States

Developing a neuroimaging tool that can determine the normalcy of a multi-contrast MR examination will be useful in clinical practice. In a given radiology department, close to 50% of all MRI examinations are read as normal by the staff radiologists. Here, we describe a z-score based method which reduces the entire MRI examination to a single number, which can be used to determine the disease state. We have applied this methodology to two groups of patients (schizophrenia and bipolar disease) and two groups of matched healthy controls. We show that although the clinical MR imaging was not diagnostic, we can separate the patient groups from controls using this method.

Napapon Sailasuta¹, Yusuke Iwata¹, Shinichiro Nakajima¹, Sofia Chavez¹, Fernando Caravaggio¹, Eric Plitman¹, Vincenzo De Luca¹, Jun Ku Chung¹, Philip Gerretsen¹, Gary Remington¹, and Ariel Graff-Guerrero^1
1The Centre for Addiction and Mental Health, toronto, ON, Canada

Our current stuty is aimed to compare Glutathione (GSH) levels between in patients with Schizophrenia (Sz) and healty controls (HC) quantified in the ACC employing a validated J-editing quantification method.GSH levels were quantified with 1H-MRS. Our pilot data demonstrated lower levels of GSH/H2O in ACC in patients with Sz compared with HC (P= 0.0002).

Petr Menschikov¹, Natalia Semenova^1,2, Maxim Ublinskii³, Dmitry Kupriyanov⁴, Irina Lebedeva⁵, Maria Omelchenko⁵, and Tolibjon Akhadov^3
1N.N. Semenov Institute of Chemical Physics of the Russian Academy of Sciences, Moscow, Russian Federation, ²N.M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow, Russian Federation, ³Children's Clinical and Research Institute of Emergency Surgery and Trauma, Moscow, Russian Federation, ⁴Philips Healthcare Russia, Moscow, Russian Federation, ⁵National Mental Health Research Centre of the Russian Academy of Medical Sciences, Moscow, Russian Federation

It was reported previously that GLX is reduced in anterior cingulate (AC) for chronic schizophrenia patients medicated with antipsychotic drugs. Reduction of GLX in right hemisphere in our study reflects changes in the metabolic system as a consequence of the illness itself, without influence of treatment with antipsychotics or age changes. We assume also that left AC GABA reduction observed in our study is typical for schizophrenia development - previously reported unchanged GABA in AC of young chronic medicated patients could be associated with an effect of antipsychotic medication.

Anouk Marsman¹, Subechhya Pradhan¹, Candice Ford², Ashley Lloyd², Teppei Tanaka², Akira Sawa², and Peter B. Barker^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States,²Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

The glutamatergic system plays a role in the pathophysiology of schizophrenia. N-acetyl-aspartyl-glutamate (NAAG) modulates this system and may therefore be implicated in schizophrenia. Interim analyses of an ongoing study show that patients with first-episode psychosis show significantly (p<0.05) lower NAAG levels and NAAG/NAA ratios in the centrum semiovale as compared to healthy matched controls. This could be due to altered activity of glutamate carboxypeptidase II (GCP2), which converts NAAG into N-acetyl-aspartate (NAA) and glutamate, and regulates synaptic NAAG concentrations.

Chen-Hao Wu^1,2, Yu-Jen Chen², Yun-Chin Hsu², Yu-Chun Lo², Tzung-Jeng Hwang³, Hai-Gwo Hwu³, Chung-Ming Chen¹, and Wen-Yih Isaac Tseng^1,2
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan, ²Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

Altered white matter tract integrity in drug-naïve and chronic schizophrenia patients: a study using automatic tract-specific analysis of the whole brain

Ming Zhou¹, Xinyu Hu¹, Junmei Hu², Qi Liu¹, Lizhou Chen¹, Qiyong Gong¹, and Xiaoqi Huang^1
1West China Hospital of Sichuan University, Huaxi MR Research Center, Chengdu, Sichuan, China, ²Sichuan University, School of Basic Science and Forensic Medicine, Sichuan, China

we demonstrated defects in cerebellum, striatum and precuneus were associated with a wide range of schizophrenia symptoms and violent behavior by the use of functional connectivity approach.

Miao Yu¹, Xiangrong Zhang^1,2, Xiaowei Tang³, Zhengjia Dai⁴, Xiang Wang⁵, Xiaobin Zhang³, Weiwei Sha³, Shuqiao Yao⁵, Yong He⁴, and Zhijun Zhang^1
1Department of Neuropsychiatry Affiliated ZhongDa Hospital of Southeast University, Nanjing, JiangSu, China, ²Department of Geriatric Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, JiangSu, China, ³Department of Psychiatry, Wutaishan Hospital of Yangzhou, JiangSu, China, ⁴State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China, ⁵Medical Psychological Institute of the Second Xiangya Hospital, Central South University, HuNan, China

Investigate commonalities and distinctions of the topological abnormalities in deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients compared with healthy controls (HC) by using graph theory in resting-state functional magnetic resonance imaging (fMRI).

Yan-Lin Chiu^1,2, Su-Chun Huang², Chih-Min Liu³, Tzung-Jeng Hwang³, Hai-Gwo Hwu³, Yung-Chin Hsu², Yu-Chun Lo², Yu-Jen Chen², and Wen-Yih Isaac Tseng^2,4
1School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ²Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, ⁴Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

In the present study we found that fornix is an important tract when investigating the white matter microstructural changes of schizophrenia. Decreased GFA values of bilateral fornix were found in patients group. Moreover, the correlations of clinical symptoms and GFA of fornix showed entirely different patterns between FE and chronic patients. We hypothesize that the phenomenon may be a complex interaction of medication-related changes and natural disease progress. For future works, we plan to do long term follow-up with detailed medication history of the patients to ascertain the effects of antipsychotic medications.

Xinyu Hu¹, Yi Liao¹, Lizhou Chen¹, Lei Li¹, Ming Zhou¹, Qi Liu¹, Junmei Hu², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), Department of Radiology,West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China

The association between schizophrenia and violent behavior has significant clinical and social implications. Although previous studies had proved that alterations in the basal ganglia, predominantly the striatum, constitute important characteristics of neural pathology in schizophrenia, the relationship between functional connectivity of striatum and severely violent behaviors still remains unknown. The aim of the current study is to explore the characteristic functional connectivity in a subgroup of schizophrenia patients with severe violent behavior and its relationship with clinical measurements.

Neurovascular - Stroke

Tuesday 2 June 2015

Qian Wang^1,2, Yunxia Li^1,3, Eric R Muir¹, Qiang Shen¹, Shiliang Huang¹, and Timothy Q Duong^1
1Research Imaging Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Xiang Ya School of Medicine, Central South University, Changsha, China, ³Department of Neurology, Tongji Hospital, Tongji University, Shanghai, China

The goal of this study was to investigate the effects of hypertension on the optic tract and retinal nerve fiber layer thickness in the established rat model of hypertension (SHR). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In conclusion, we found evidence that chronic hypertension damage white matter in the optic tract (as indicated by FA disruption and immunohistology) and retina (as indicated by retinal nerve fiber layer and vascular diameter changes) in an established animal model of hypertension.

Erin L Mazerolle¹, Yuhan Ma², David Sinclair², and G Bruce Pike^1
1University of Calgary, Calgary, Alberta, Canada, ²McGill University, Montreal, Quebec, Canada

We investigated task-related hemodynamics in moyamoya disease (MMD). Patients with MMD exhibit abnormal cerebrovascular reactivity in anterior brain regions, which we predicted would be associated with neurovascular uncoupling. We compared BOLD fMRI activation maps among tasks with varying extents of associated vascular demands. For tasks associated with extensive vascular demands, we found atypically low activation in MMD-affected brain regions, reflective of neurovascular uncoupling. This activation could be partially or completely recovered when the total extent of the task’s vascular demands was reduced. Thus, the potential effects of neurovascular uncoupling must be considered in patients with cerebrovascular disease.

Philipp Kaesemann¹, Götz Thomalla², Bastian Cheng², Andras Treszl³, Jens Fiehler⁴, and Nils Daniel Forkert^5
1Department of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ²Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany, ³Department of Medical Biometrics and Epidemiology, University Medical Center Hamburg-Eppendorf, Germany,⁴Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany, ⁵Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada

The effect of a long-lasting internal carotid artery (ICA) stenosis on the diffusion and perfusion situation in patients with an acute ischemic stroke is not well understood. Within this context, it may be hypothesized that an ICA stenosis leads to a more severe hypoperfusion situation. On the other hand, an ICA stenosis may be even beneficial in case of an acute stroke due to a prior development of an improved collateral situation or preconditioning of the brain tissue. The objective of this study was to compare lesion volumes as well as diffusion and perfusion parameters in acute ischemic stroke patients with or without a coexisting ICA stenosis.

Sunil Koundal^1,2, Sonia Gandhi¹, Tanzeer kaur², and Subash Khushu^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi, Delhi, India, ²Department of Biophysics, Panjab University, Chandigarh, India

Chronic hypobaric hypoxia induced metabolic alterations in brain hippocampus was studied using high resolution 600MHz NMR spectrometer. The alterations in metabolites may have altered due to change in neuronal structure, altered cellular bioenergetics and osmolarity. Further, our results can be correlated with in vivo and behavioral studies to detect if these alterations have effect on memory functions of brain for risk assessment & early diagnosis.

Vanessa L Palmer¹, Sheryl L Herrera², Jonathan D Thiessen^3,4, Shenghua Zhu⁵, Richard Buist⁶, Xin-Min Li⁷, Marc R Del Bigio⁸, and Melanie Martin^9,10
1Biomedical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada, ²Physics & Astronomy, University of Mantioba, Winnipeg, Manitoba, Canada,³Imaging Program, Lawson Health Research Institute, London, Ontario, Canada, ⁴Medical Biophysics, Western University, London, Ontario, Canada, ⁵Pharmacology & Therapeutics, University of Mantioba, Winnipeg, Manitoba, Canada, ⁶Radiology, University of Mantioba, Winnipeg, Manitoba, Canada, ⁷Psychiatry, University of Alberta, Edmonton, Alberta, Canada, ⁸Pathology, University of Mantioba, Winnipeg, Manitoba, Canada, ⁹Physics, University of Winnipeg, Winnipeg, Manitoba, Canada, ¹⁰Biomedical Engineering, Physics &Astronomy, Pharmacology &Therapeutics, Radiology, University of Mantioba, Winnipeg, Manitoba, Canada

DTI, qMTI, and multicomponent T2 relaxometry might help quantify changes related to white matter (WM) damage. To understand the interplay MRI methods have as WM changes in the corpus callosum and external capsule of the cuprizone mouse model, in vivo T2w images and MTI were acquired weekly in control and cuprizone-fed mice. Weekly DTI, qMTI, T1/T2 relaxometry, T2w imaging, and EM were used to analyze ex vivo tissue after each week of cuprizone delivery. The addition of weekly ex vivo tissue analysis allows for a more complete understanding of the correlations between MR metrics and EM measures of tissue pathology.

Haikun Qi¹, Peng Liu², Hansen Li¹, and Huijun Chen^1
1Department of Biomedical Engineeing, School of Medicine, Tsinghua University, Beijing, Beijing, China, ²Department of Neurosurgical, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Beijing, China

Saccular intracranial aneurysm (IA) rupture risk prediction is critical in the IA treatment decision-making process. 3D High resolution MR black blood vessel wall imaging has great potential for IA risk stratification with the ability for both IA size measurement and aneurysm wall inflammation evaluation. In this study, the IA size measured by 3D black blood T1-VISTA images is validated by comparing with 3D CTA measurement and excellent agreement was found. The IA wall enhancement was evaluated based on pre- and post-contrast VISTA images, and prevalence of IA wall enhancement was reported.

Lisa M Gazdzinski¹, Lindsay S Cahill¹, Yu-Qing Zhou¹, Albert KY Tsui^2,3, Gregory MT Hare^2,3, Andrea Kassner^4,5, and John G Sled^1,6
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, ²Department of Anaesthesia, St. Michael's Hospital, Toronto, Ontario, Canada,³Keenan Research Centre for Biomedical Science, University of Toronto, Ontario, Canada, ⁴Department of Medical Imaging, University of Toronto, Ontario, Canada,⁵Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada, ⁶Department of Medical Biophysics, University of Toronto, Ontario, Canada

Sickle cell disease (SCD) is associated with neurocognitive impairment and an increased risk of stroke. The mechanisms are poorly understood, but likely involve increased cerebral blood flow (CBF) and decreased cerebrovascular reserve (CVR). This study uses CASL to characterize CBF and CVR in a transgenic mouse model of SCD, demontrating that the model recapitulates important pathophysiological features of the disease. Brain morphometry is also performed using high-resolution MRI, showing localized volume differences throughout the brain in SCD mice. The model characterized here will be invaluable for developing an understanding of the mechanisms behind stroke and neurocognitive impairment in SCD.

Venkata Veerendra Nadh Chebrolu¹, Dattesh Shanbhag¹, Patrice Hervo², Marc-Antoine Labeyrie³, Catherine Oppenheim³, and Rakesh Mullick^4
1Medical Image Analysis Lab, GE Global Research, Bangalore, Karnataka, India, ²GE Healthcare, Buc, France, ³Centre Hospitalier, Sainte-Anne, Paris, France,⁴Diagnostics & Biomedical Technologies, GE Global Research, Bangalore, Karnataka, India

Multiple approaches have been proposed for segmenting the diffusion lesion in the acute phase of the ischemic stroke. The same algorithms may not be accurate for segmenting the diffusion lesion on the data obtained one day after treatment (day 1 diffusion lesion). In this work, we analyze the diffusion lesion’s apparent diffusion coefficient (ADC) and DWI characteristics after treatment and compare them with the diffusion lesion characteristics within 4.5 hours of ictus (day 0 diffusion lesion). We also analyze the sensitivity and specificity of different linear classification methods in segmenting the day 1 diffusion lesion using Receiver Operating Characteristic analysis.

J. Mitra¹, P. Bourgeat¹, J. Fripp¹, O. Salvado¹, B. Campbell², S. Palmer³, P. Goodin³, A. Connelly^3,4, S. Rose¹, L. Carey^3,4, and the START Program Team^5
1Australian e-Health & Research Centre, CSIRO Digital Productivity Flagship, Herston, QLD, Australia, ²Department of Radiology, The Melbourne Brain Centre at the Royal Melbourne Hospital, VIC, Australia, ³The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia, ⁴La Trobe University, Bundoora, VIC, Australia, ⁵http://www.START.csiro.au, VIC, Australia

Cerebral white matter is especially vulnerable to hypoxic-ischemic injury, resulting in white matter lesions. Knowledge of how brain networks are interrupted is currently limited, but critical to better understanding the nature of the clinical deficit and stroke recovery. We used diffusion-weighted MRI and probabilistic tractography to identify the common neural pathways affected in stroke patients, with a view of predicting cognitive and functional deficits associated with the affected areas. Our hypothesis is that loss in connectivity in these common regions will correlate with the clinical measurements of cognition, sensorimotor function and disability.

Sinyeob Ahn¹, Henrik Haraldsson^2,3, Chengcheng Zhu^2,3, John Grinstead⁴, David Saloner^2,3, and Gerhard Laub^1
1Siemens Healthcare, San Francisco, CA, United States, ²Radiology, Veterans Affairs Medical Center, San Francisco, CA, United States, ³Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ⁴Siemens Healthcare, Portland, OR, United States

Imaging and assessment of arterial vessel wall is challenging due to its small dimension and appropriate imaging technique has not been well established for this application. Recently, 3D turbo spin echo sequence (SPACE) has been used to provide high-resolution image quality within a feasible scan time. However, a long echo train which is typically used to shorten scan time may lead to image artifacts. In this paper, we report the effect of the wall edge enhancement and broadening by signal acquired during echo train. The basilar arterial wall was imaged and studied in comparison with analytical simulation results.

Lei Zhang¹, Jianping Jia², Yiu-Cho Chung¹, Qi Yang³, Xin Liu¹, Ying Han², and Xiaodong Zou^2
1Paul C. Lauterbur Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academic of Sciences, Shenzhen, Guangdong, China,²Neurology, Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China, ³Radiology, Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China

Single subcortical infarction (SSI) in middle cerebral artery (MCA) territory has been considered to be mainly caused by lipohyalinosis or atherosclerosis. We investigated the presence of MCA plaques in patients with SSI using three-dimensional (3D) high-resolution black-blood MRI imaging, and found that atherosclerosis was more prevalent than commonly thought among patients with SSI. Meanwhile, Ipsilateral MCA had higher frequencies of atherosclerotic than contralateral side, most of which were superiorly located. 3D HR-MRI can noninvasively in vivo providing detailed information of intracranial atherosclerotic plaques with broad coverage in approximately 6 min and could strengthen our comprehension of SSI mechanism.

Cheng-Yu Peng¹, Ying Cui¹, Deng-Ling Zhao¹, Yun Jiao¹, Shenghong Ju¹, and Gao-Jun Teng^1
1Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospita, Nanjing, Jiangsu, China

A stroke can increase the risk of vascular cognitive impairment. This study utilised resting-state fMRI to investigate regional homogeneity (ReHo) changes in subcortical stroke patients and whether these changes were correlated with cognitive performance. The stroke patients exhibited significant deficiencies in relevant cognitive domains and also demonstrated significantly aberrant ReHo values in some specific brain regions compared with the healthy controls. Moreover, the ReHo values of the right superior temporal gyrus/middle temporal gyrus were significantly correlated with the cognitive test scores in the stroke group. ReHo could represent a promising tool for the observation of neurobiological consequences in post-stroke patients.

Rosario Lopez-Gonzalez¹, Sin Yee Foo², William M Holmes³, William Stewart⁴, Keith Muir⁵, Barrie Condon⁶, George Welch⁷, and Kirsten Forbes^8
1Clinical Physics and Bioengineering, NHS, Glasgow, Glasgow, United Kingdom, ²School of Medicine, University of Glasgow, Glasgow, United Kingdom, ³GEMRIC, Institute of Neuroscience and Psychology, Glasgow, United Kingdom, ⁴Neuropathology, NHS, Glasgow, United Kingdom, ⁵Division of Clinical Neurosciences, University of Glasgow, Glasgow, United Kingdom, ⁶NHS, Glasgow, United Kingdom, ⁷Vascular Surgery, NHS, Glasgow, United Kingdom, ⁸Institute of Neurological Sciences, NHS, Glasgow, United Kingdom

This study aims to evaluate the ability to identify all major carotid plaque components using ex-vivo 7T MRI and correlation with histology. Surgical excision of atherosclerotic carotid plaque (carotid endarterectomy, CEA), based on the extent of luminal narrowing, reduces risk of subsequent stroke. However, 70% of patients with severe stenosis remain stroke-free over the next 5 years with medical therapy alone. Outcomes from CEA could be improved by targeting treatment at high-risk subgroups. Atherosclerotic plaque morphology and plaque composition may identify unstable or vulnerable plaque that defines higher risk.

Tianyi Qian¹, Zhiwei Zuo², Josef Pfeuffer³, Yuehua Pu⁴, Penggang Qiao², Liping Liu⁴, and Gongjie Li^2
1MR Collaborations NE Asia, Siemens Healthcare, Beijing, Beijing, China, ²Radiology, Affiliated hospital of Academy of Military Medical Sciences, Beijing, China,³Application Development, Siemens Healthcare, Erlangen, Germany, ⁴Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

A 3D multi-TI arterial spin-labeling (mTI-ASL) protocol had been applied to measure the blood perfusion of stroke patients. Both the bolus arrival time and relCBF obtained from fitting the hemodynamic response curve were agreed with the results of CT perfusion. The accurate timing and relCBF obtained by mTI-ASL could provide valuable information for evaluating collateral circulation.

James Duffin^1,2, Olivia Sobczyk³, David J Mikulis^3,4, and Joseph A Fisher^1,2
1Department of Physiology, University of Toronto, Toronto, Ontario, Canada, ²Department of Anaesthesia and Pain Management, University Health Network, Toronto, Ontario, Canada, ³Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada, ⁴Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Ontario, Canada

The cerebrovascular reactivity (CVR) to a stimulus assesses the health of the cerebovasculature. When measured with MRI, the resulting CVR values for each voxel can be displayed using a color scale mapped onto the corresponding anatomical scan to generate CVR maps showing the distribution of the vascular responses. However, such CVR maps estimate only the magnitude, and do not indicate the time course of the response; whether rapid or slow. Transfer function analysis provides not only the magnitude of the response but also the phase, an indicator of the response dynamics, as well as a measure of the fidelity with which the response follows the stimulus.

Lijuan Zhang¹, Caiyun Shi¹, Chunxiang Jiang¹, Li Yi², Guoxi Xie¹, Xiaojing Long¹, and Yang Liu^2
1SIAT, Chinese Academy of Sciences, Shenzhen, Guangdong, China, ²Peiking University Shenzhen Hospital, Guangdong, China

Ischemic stroke (IS) leads to local metabolic and functional impairment in the vicinity of the lesion. However, the global effect of IS remains to be clarified.In this study we presented the global effect of IS by estimating the cerebral oxygen extraction fraction (OEF) based on the magnetic resonance susceptibility weighted imaging.This preliminary study may provide a meaningful reference for future researches towards a better understanding of the disease dynamic of IS.

Liu Chunming¹, Xu Liang¹, Dong Longchun¹, Zuo Panli², Pfeuffer Josef³, and Liu Jun^1
1Department of radiology, Tianjin union medicine centre, Tianjin, Tianjin, China, ²Siemens Healthcare, MR Collaborations NE Asia, Beijing, China, ³Siemens Healthcare, Application Development, Berlin, Germany

Using multi-TI arterial spin labeling sequence with 3D GRASE readout for perfusion imaging in ischemic stroke to calculate the relative cerebral blood flow (relCBF) and bolus arrival time (BAT), and to compare with dynamic susceptibility contract perfusion weighted MR imaging (DSC)

Ana-Maria Oros-Peusquens¹, Omid Nikoubashman², Johannes Lindemeyer¹, Markus Zimmermann¹, Martin Wiesmann², and N. Jon Shah^1
1Institute of Neuroscience and Medicine (INM-4), Research Centre Juelich, Juelich, Germany, ²Faculty of Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany

Changes in water content are highly relevant for the characterisation of disease, but they are usually in the low percentage range, requiring methods with high accuracy for detection. We report here on such a method and apply it to healthy volunteers and a patient with subacute stroke. The aim of the study is to establish a quantitative method for monitoring of the evolution of oedema in stroke.

Dinesh Gooneratne¹, Yuliya Perchyonok^1,2, Greg Fitt¹, Andrew Kemp³, Tim Spelman⁴, Shivraman Giri⁵, Davide Piccini⁶, Robert R Edelman⁷, Marion Simpson⁸, Helen Dewey^8,9, Geraldine Ng⁸, Ioannis Koktzoglou⁷, and Ruth P Lim^1,2
1Radiology department, Austin Hospital, Melbourne, Victoria, Australia, ²Melbourne University, Victoria, Australia, ³Austin Hospital, Victoria, Australia, ⁴Burnet Institute, Victoria, Australia, ⁵Siemens Healthcare USA, Pennsylvania, United States, ⁶Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI, Lausanne, Switzerland, ⁷NorthShore University HealthSystem, Illinois, United States, ⁸Neurology Department, Austin Hospital, Victoria, Australia, ⁹Neurology Department, Eastern Health, Victoria, Australia

A Non-enhanced Hybrid Arterial Spin Labeling MRA (NoHASL MRA) technique for assessment of the extracranial cervical arteries was evaluated. 15 patients with suspected cerebral ischemia underwent NoHASL followed by contrast enhanced MRA (CE-MRA). 18 arterial segments were assessed by 2 neuroradiologists for diagnostic confidence, internal carotid artery and vertebral artery stenosis against CE-MRA as the reference standard. There was no significant difference between dichotomized diagnostic and non-diagnostic confidence scores for the ICA, with moderate correlation between ICA bulb absolute diameters. NoHASL shows promise as a relatively rapid, non contrast sequence for assessment of cervical arterial disease.

Randall B Stafford^1,2, Cheryl R McCreary^2,3, Anna Charlton¹, Angela Zwiers¹, X Rachel Wang^1,2, Ikreet Cheema^2,4, Saima Batool^1,2, Zahinoor Ismail^1,5, Bradley G Goodyear^2,3, Richard Frayne^2,3, and Eric E Smith^1,3
1Clinical Neurosciences, University of Calgary, Calgary, AB, Canada, ²Seaman Family MR Research Centre & Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ³Radiology, University of Calgary, Calgary, AB, Canada, ⁴Neuroscience, University of Calgary, Calgary, AB, Canada, ⁵Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

Cerebral amyloid angiopathy (CAA) is caused by vascular beta-amyloid deposition, which can lead to several clinical conditions including hemorrhage, microinfarcts, and compromised vascular reactivity. Our hypothesis is that patients with CAA exhibit reduced cortical gray matter volume and hypoperfusion in the occipital lobes, which are often affected by CAA. We used a multi-modal MR protocol that included a high-resolution T1 anatomical acquisition, a T2-FLAIR acquisition, and a resting pseudo-continuous ASL acquisition. Our results did not show any difference in perfusion between participants with CAA and health age-matched controls, however we did find reduced cortical gray matter volume in CAA.

Huan Tan¹, Abdul Ghani Mikati¹, Lingjiao Zhang¹, Tian Liu², Yi Wang³, Robert R Edelman^4,5, Gregory A. Christoforidis¹, and Issam A. Awad^1
1Surgery, University of Chicago, Chicago, IL, United States, ²MedImageMetric LLC, New York, NY, United States, ³Weill Cornell Medical College, New York, NY, United States, ⁴NorthShore University HealthSystem, Evanston, IL, United States, ⁵Northwestern University Feinberg School of Medicine, Chicago, IL, United States

We have previously demonstrated the feasibility of using quantitative susceptibility mapping (QSM) for lesional iron quantification in patients with cerebral cavernous malformations (CCM). In this study, we correlated mean susceptibility measurements with patient’s clinical activities and we found: 1) older lesions harbor more iron deposition; 2) lesions that has bled previously contain more iron deposition; 3) longitudinal changes in lesional iron deposition were small in patients who are clinically stable in a short time frame (<1.5 years).

Andrew D. Robertson¹, David E. Crane¹, A. Saeed Rajab^1,2, Walter Swardfager^1,3, Susan Marzolini^1,3, Laura E. Middleton^3,4, and Bradley J. MacIntosh^1,2
1Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada, ²Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Toronto Rehabilitation Institute, University Health Network, University of Toronto, Toronto, ON, Canada, ⁴University of Waterloo, Department of Kinesiology, Waterloo, ON, Canada

We examined how exercise intensity affects cerebral blood flow (CBF) following acute cycling in stroke. Using arterial spin labeling, CBF estimates were made before, 30 min after, and 50 min after exercise. Participants exercised at low and moderate intensities on separate days. CBF was changed after cycling, independent of intensity, in areas within the right basal ganglia and frontal lobe, and left temporal and parietal lobes. The right parietal lobe, in particular, was sensitive to intensity. In three areas, CBF increased after moderate intensity cycling, relative to light exercise. Parietal regions may provide a sensitive biomarker for exercise-based stroke rehabilitation.

Liya Wang^1,2, Adrian Lam³, John Oshinski², Xiaodong Zhong⁴, Chad A Holder², Felicia Goldstein⁵, Diana Ge², and Hui Mao^1,2
1Laboratory of Functional-Molecular Imaging and Nanomedicine, Emory University School of Medicine, Atlanta, Georgia, United States, ²Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, United States, ³Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States, ⁴MR R&D Collaborations, Siemens Healthcare, Atlanta, Georgia, United States, ⁵Neurology, Emory University School of Medicine, Atlanta, Georgia, United States

Cerebrovascular diseases may cause cognitive functions decline. Comprehensive MRI approaches used to characterize white matter hyperintensity (WMH), cerebral blood flow (CBF), and vertebral artery (VA) stenosis in patients with cerebral vascular and cardiovascular risks. It demonstrated that VA stenosis characterized as vascular narrowing and/or reduced CBF by MRI may be associated with the regional specific cerebral vascular comorbidities detected as WMH and reduction of CBF. The comprehensive MRI protocols with functional and high resolution structural imaging sequences are capable of providing valuable information on blood flow supply in the VA and cerebrovascular ischemia in individuals having vertebral and cardiovascular abnormalities.

Diandian Huang¹, Jing Zhang¹, Ting Wang¹, Yanhua Li², Bensheng Qiu³, Xiaoxuan He³, Zhenyu Zhou⁴, Bing Wu⁴, Lin Ma¹, and Xin Lou^1
1Department of Radiology, Chinese PLA General Hospital, Beijing, Beijing, China, ²Department of cardiology, Chinese PLA General Hospital, Beijing, China,³Department of Electronic Science and Technology, University of Science and Technology of China, Anhui, China, ⁴MR Research Center, GE Health care, Beijing, China

Hypertensive group without retinopathy and control group were recruited from the primary care and had a MR scan with the three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and routine sequences. Compared to the control group, hypertensive patients implied the reduced CBF values on visual cortex without the statistical volume loss which may implicated there is a variety of the hemodynamics prior to the change of the morphology in the visual cortex in hypertension. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early visual cortex perfusion deficits observed.

Neurovascular Disease

Tuesday 2 June 2015

Thomas Christen¹, Samantha Holdsworth¹, Hesamoddin Jahanian¹, Hua Wu², Kangrong Zhu³, Adam Kerr³, Matthew J Middione⁴, Robert F Dougherty², Michael Moseley¹, and Greg Zaharchuk^1
1Department of Radiology, Stanford University, Stanford, California, United States, ²Center for Cognitive and Neurobiological Imaging, Stanford University, Stanford, California, United States, ³Department of Electrical Engineering, Stanford University, Stanford, California, United States, ⁴Applied Sciences Laboratory West, GE Healthcare, Menlo Park, California, United States

In this work, we acquired whole brain, high-temporal resolution (TR=350ms) resting-state BOLD fMRI data in volunteers and Moyamoya patients using a Simultaneous MultiSlice (SMS)-EPI technique. Using seed signals chosen from blood vessels or the precuneus region and after correlation analyses across different parts of the frequency spectrum, we derived functional network maps, blood volume-weighted images, and blood arrival time.

Ligia SIMOES BRAGA BOISSERAND^1,2, Benjamin LEMASSON¹, Lydiane HIRSCHLER^1,2, Violaine HUBERT¹, Anaïck MOISAN¹, Emmanuel BARBIER^1,2, Chantal REMY^1,2, and Olivier DETANTE^1,2
1Inserm U836, Grenoble, -, France, ²Université Grenoble Alpes, Grenoble, -, France

In acute stroke, to discriminate non-salvageable (ischemic core) from salvageable (penumbra) tissue remains an important goal. Diffusion-MRI hypersignal (severe decrease of apparent diffusion coefficient (ADC)) overestimate the core, and perfusion-MRI only provides qualitative data still debated. Thus, we studied hemodynamic and oxygenation changes during cerebral ischemia using blood oxygen level-dependent (BOLD) MRI with a quantitative approach (ADC; Blood Volume fraction, BVf; local Oxygen Saturation, lSO2).

Akira Kunimatsu¹, Yasushi Watanabe², Mitsuharu Miyoshi³, Kouhei Kamiya¹, Masaki Katsura², Harushi Mori¹, Hiroyuki Kabasawa³, and Kuni Ohtomo^1
1Department of Radiology, The University of Tokyo, Tokyo, Japan, ²Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan, ³GE Healthcare, Tokyo, Japan

We assessed clinical utility of post-contrast CUBE T1 with MSDE preparation in the evaluation of patients with cerebral arteriovenous malformations (AVMs). We found improved detectability of vessel wall enhancement and perivascular parenchymal enhancement of abnormal vessels of AVMs on post-contrast CUBE T1 with MSDE, compared with post-contrast 3D FSPGR without MSDE. Post-contrast CUBE T1 with MSDE preparation may be useful to confirm therapeutic effects early after radiotherapy for cerebral AVMs.

Won Beom Jung^1,2, Geun Ho Im^1,2, Sun Young Chae³, Yong Hee Han^1,2, and Jung Hee Lee^1,3
1Department of Radiology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, ²Center for Molecular and Cellular Imaging Samsung Biomedical Research Institute, Seoul, Korea, ³Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University, Seoul, Korea

In this study, we examined the functional and anatomical brain changes in perinatal hypoxic ischemic injured rat brain with BOLD-fMRI, DTI and rs-fMRI. HI injured brains were observed with the the widespread sensory-motor related areas on intact forelimb, weakly evoked brain activation on impaired forelimb, intra-hemispheric track rewiring and enhanced intra-connectivity in cingulate cortex areas compared with sham-operated brains. In addition, impared forelimb show the behavioral perfomance although not complete. We believe that brain modulations in HI induced rats are the neuralplasticity for spontaneous recovery to compensate for functional loss.

Yunxia Li^1,2, Qiang Shen¹, Shiliang Huang¹, Wei Li¹, Eric R Muir¹, 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, ²Department of Neurology, Tongji Hospital, Tongji University, Shanghai, China

Chronic hypertension increases susceptibility to neurological disorders. The goal of this study was to evaluate cerebral blood flow (CBF) and cerebrovascular reactivity (CR) in response to hypercapnia in an established rat model of hypertension (SHR) at different stages of the disease progression. Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. CBF and CR were altered in early stage of chronic hypertension and worsen with disease progression, ultimately resulting in hypoperfusion and compromised cerebrovascular reserve. MRI has the potential to be used to identify brain regions susceptible to hemodynamic compromise, improve understanding of disease pathogenesis, guider treatments in hypertension.

Yeji Han¹, Eung Yeop Kim², Yeon Chul Ryu³, and Jun-Young Chung^1
1Department of Biomedical Engineering, Gachon University, Incheon, Incheon, Korea, ²Radiology, Gachon University Gil Medical Center, Incheon, Korea,³Neuroscience Research Institute, Gachon University, Incheon, Incheon, Korea

Recent works have shown that the T2*-weighted conventional GRE sequences may be the best method for detecting cerebral diseases, such as cerebral venous thrombosis and it would seem to be beneficial to integrate a T2*-weighted conventional GRE sequence into the MR protocol to diagnose cerebral venous thrombosis. To integrate yet another scanning sequence to the routine protocol, the most important concern lies in the increased examination time. In this study, a simultaneous method of acquiring both T2* and phase-contrast (PC) angiography is proposed.

Yunxia Li^1,2, Shiliang Huang¹, Qiang Shen¹, Eric R Muir¹, and Timothy Q Duong^1
1Research Imaging Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Department of Neurology, Tongji Hospital, Tongji University, Shanghai, China

Magnetic resonance imaging (MRI) has been widely used to study neurovascular coupling and evoked responses under normal conditions and in neurological diseases in vivo. Chronic hypertension will change the function of brain. The goal of this study is to use MRI to evaluate the effects of chronic hypertension on BOLD and CBF responses to hypercapnic challenge, and BOLD, CBF responses to forepaw stimulation in the in vivo in spontaneously hypertensive rats. 40 weeks SHR has the compromised cerebravascular response to hypercapnia challenge, which should come from the hypertensive damage to cerebral vascular. The greater fMRI responses to forepaw stimulation are correlated with the higher blood pressure.

Julien Poublanc¹, Adrian Crawley¹, Olivia Sobczyk², Gaspard Montandon¹, Kevin Sam¹, Daniel Mandell¹, Lakshmikumar Venkatraghavan³, James Duffin³, David Mikulis¹, and Joseph Fisher^3
1Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada, ²Institute of Medical Sciences, Ontario, Canada, ³Department of Anaesthesia and Physiology, University Health Network, Toronto, Ontario, Canada

In this study, we investigated the dynamic aspect of the BOLD cerebrovascular reactivity response to a change in end-tidal PCO₂ by developing a reliable method to measure its time characteristic,. In healthy subjects, the mean  value in grey (GM) and white (WM) was respectively 20.2±10.5s and 40.7±10.7s. In patients,  is significantly prolonged (= 38.64±8.42s, p < 0.001) in GM with positive CO₂ reactivity, ipsilateral to a stenosis. In the future, this method could be applied for investigating a variety of diseases that affect the cerebral vasculature or alter neurovascular coupling.

Pei-Shan Ho^1,2, Ting-Yu Chang³, Meng-Yang Ho⁴, Chang-Wei Wu⁵, Kuo-Lun Huang³, Ho-Fai Wong⁶, Tsong-Hai Lee³, and Ho-Ling Liu^1,7
1Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ²Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ³Department of Neurology and Stroke Center, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taoyuan, Taiwan, ⁴Department of Occupational Therapy, Chang Gung University, Taoyuan, Taiwan, ⁵Graduate Institute of Biomedical Engineering, National Central University, Taoyuan, Taiwan, ⁶Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ⁷Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States

Severe internal carotid artery (ICA) stenosis impairs brain cognitive function, which might be originated from cerebral hypoperfusion. However, the underlying brain mechanisms remain largely unknown. This study aimed at investigating the relationship of brain functional connectivity and neuropsychology in both unilateral ICA stenotic patients (N=27) and normal subjects (N=20). We compared indicative network parameters between ICA stenotic patients and normal subjects across two hemispheres. We found lower degree and global efficiency in the ipsilateral side to the stenosis. Moreover, network parameters were positively correlated with neuropsychological tests in the patients. Our results implied that the patients with more deteriorated brain.

Kai Xu¹, LeRoy Stromberg¹, David Rusinak¹, Stephen Futterer¹, Shivraman Giri¹, James Carr¹, Robert Edelman¹, Ioannis Koktzoglou², and Jeremy Collins^1
1Radiology, Northwestern University, Chicago, IL, United States, ²Radiology, NorthShore University HealthSystem, Evanston, IL, United States

Carotid artery atherosclerosis is an important etiology of stroke, for which morphological assessment with quantitation of luminal narrowing plays a critical role in diagnosis and mangement. However, contrast-enhanced MRA and contrast-enhanced CTA are contraindicated in patients with stage 4 or 5 renal insufficiency due to the risk of nephrogenic systemic fibrosis and iodinated contrast induced nephropathy. hASL is a non-contrast MR angiographic technique which has shown promise for neurovascular assessment. In a prospective patient cohort with suspected stroke, hASL MRA excluded carotid artery stenosis as an etiology, demonstrating excellent agreement with contrast-enhanced MRA.

Irene Klærke Mikkelsen¹, Lars Riisgaard Ribe¹, and Leif Østergaard^1
1Center for functionally integrative neuroscience, Aarhus University, Aarhus, Denmark

In acute stroke patients, the penumbra indicates tissue-at-risk. The corresponding imaging marker is the mismatch between abnormal regions on perfusion-weighted images (PWI) and diffusion-weighted images (DWI). The PWI-abnormality is affected, if imaging duration is too short to capture the entire passage of contrast agent through the tissue. We simulated bolus truncation in 73 patients, and found that penumbra would have been overlooked in 22 patients, had imaging duration been 15s after peak of the arterial curve. This number reduced with imaging duration, or if a vascular model for was used for perfusion-calculation. A BT indicator was suggested for quality assessment.

Yasutaka Fushimi¹, Koji Fujimoto¹, Tomohisa Okada¹, Akira Yamamoto¹, Takayuki Yamamoto¹, Tai Akasaka¹, Kei Sano², Toshiyuki Tanaka², and Kaori Togashi^1
1Kyoto University Graduate School of Medicine, Kyoto, Japan, ²Department of Systems Science, Kyoto University Graduate School of Informatics, Kyoto, Japan

Optimization of compressed sensed 3D TOF-MRA with NESTA algorithm was conducted and the best parameter was applied for cerebral aneurysms.

Aurelien F Stalder¹, Yutaka Natsuaki², Michaela Schmidt¹, Xiaoming Bi², Michael O Zenge³, Mariappan Nadar⁴, Peter Speier¹, Peter Schmitt¹, and Gerhard Laub^2
1Siemens Healthcare, Erlangen, Germany, ²Siemens Healthcare, CA, United States, ³Siemens Healthcare, NY, United States, ⁴Siemens Corporate Technology, NJ, United States

According to the sparse MRI theory, improved incoherence should allow better performance with iterative reconstruction techniques. In this work, we implemented a sparse TOF MRA technique using a variable Poisson density sampling scheme on a standard clinical scanner. Thanks to the improved incoherence of the sampling pattern, it was possible to acquire high-quality and artifact-free images in volunteers and patients in 45% shorter scan times compared to conventional TOF imaging with parallel imaging. This work demonstrates the feasibility of sparse TOF MRA with high and isotropic resolution on a standard clinical scanner in just 3:15 min.

Huilin Zhao¹, Jinnan Wang², Xiaosheng Liu¹, Xihai Zhao³, Chun Yuan⁴, and Jianrong Xu^1
1Radiology, Renji hospital, Shanghai Jiaotong University, Shanghai, Shanghai, China, ²Philips Research North America, NY, United States, ³Biomedical Engineering & Center for Biomedical Imaging Research,Tsinghua University, Beijing, China, ⁴University of Washington, WA, United States

Further understanding of the characteristics of intracranial atherosclerosis with symptomatic middle cerebral artery (MCA) steno-occlusion could be helpful for stroke risk stratification and treatment strategy modification. This study sought to assess the association between infarction pattern and size and intraplaque hemorrhage (IPH) in patients with symptomatic MCA steno-occlusion lesion. Our key findings are that 36.8% IPH characterized by SNAP imaging exist in symptomatic steno-occlusion MCA. In additon, our findings indicate that IPH together with stenosis may account for the heterogeneity of infarct sizes and patterns.

Charles G Cantrell¹, Parmede Vakil¹, and Timothy J Carroll^1
1Biomedical Engineering, Northwestern University, Chicago, Illinois, United States

Seventeen subjects were imaged using a novel rosette trajectory for imaging of OEF. We present an ICA analysis of raw free-induction decay signals, allowing us to create OEF images containing only dynamic components.

Kejia Cai^1,2, Rongwen Tain^1,2, Sandhitsu Das³, Frederick C. Damen^1,2, Yi Sui^2,4, Shika Dammala⁵, Paul Yushkevich³, Tibor Valyi-Nagy⁶, Mark A. Elliott³, and X. Joe Zhou^1,2
1Radiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ²Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ³Radiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ⁴Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States, ⁵Biology, University of Illinois at Chicago, Chicago, Illinois, United States, ⁶Neuropathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States

Although dilated perivascular spaces, also called the Virchow-Robin spaces (VRS), are found to be associated with many conditions, including aging, dementia, cerebral amyloid angiopathy, neuroinflammation, and neoplasm, it is necessary to determine whether dilated VRS is a normal variant or related to a disease process. Conventionally, such determination is mainly based on the subjective observations of the number, size and shape of the observable VRS in MR images. In this study, we developed an objective image analyzing method to quantify the brain VRS density in AD patients and age-matched healthy controls.

Przemyslaw Kosinski¹, Paula Croal², Jackie Leung², and Andrea Kassner^2,3
1Institute of Medical Science, The University of Toronto, Toronto, Ontario, Canada, ²Physiology & Experimental Medicine, The Hospital for Sick Children, Ontario, Canada, ³Medical Imaging, The University of Toronto, Toronto, Ontario, Canada

The stroke etiology in children with sickle cell anemia (SCA) is thought to be a result large-vessel stenosis. However, 32% of post-stroke children present without a history of stenosis. An alternative etiology is the hemodynamic insufficiency model which proposes that severe anemia exhausts vasodilatory capacity thus increasing the susceptibility for ischemic injury. We measured cerebrovascular reactivity (CVR) using BOLD MRI in synchrony with a hypercapnic stimulus to quantify vasodilatory capacity. Our results show that CVR is significantly associated with the degree of anemia (Hematocrit) in the gray matter (r=0.84,p<0.001) and white matter (r=0.81,p<0.001). These results favour the hemodynamic insufficiency model.

Amy Kuceyeski¹, Babak B. Navi², Hooman Kamel², Norman Relkin², Ashish Raj³, Joan Toglia⁴, Costantino Iadecola², and Michael O'Dell^4
1Radiology and the Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States, ²Neurology and the Brain and Mind Research Institute, Weill Cornell Medical College, NY, United States, ³Radiology and the Brain and Mind Research Institute, Weill Cornell Medical College, NY, United States, ⁴Rehabilitation Medicine, Weill Cornell Medical College, NY, United States

This work aims to predict three aspects of post-stroke recovery, including daily activity, cognition and basic mobility. We compare two models, one based on patient demographics and lesion volume and the other based on patient demographics and structural connectome disruption information gleaned from the Network Modification (NeMo) Tool. Models based on the NeMo tool had higher accuracy and lower Akaike Information Criterion, and also provided insight into the regions important for each of the three measured functional domains. After thorough validation, this method could be a valuable quantitative tool for clinicians in developing prognoses and rehabilitation plans for post-stroke recovery.

Zhao Jiang¹, Lora Talley Watts¹, Shiliang Huang¹, Pavel Rodriguez¹, Qiang Shen¹, and Timothy Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Methylene blue (MB) USP, which has energy-enhancing and antioxidant properties, is currently used to treat methemoglobinemia and cyanide poisoning in humans. We recently showed that MB administration reduces infarct volume and behavioral deficits in rat models of ischemic stroke and traumatic brain injury. This study reports the underlying molecular mechanisms of MB neuroprotection following transient ischemic stroke in rats.

Zhuozhi Dai^1,2, Yanlong Jia², Gen Yan², Fei Duan², Gang Xiao³, Zhiwei Shen⁴, Hongfu Sun¹, Alan H. Wilman¹, and Renhua Wu^2,4
1Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada, ²Medical Imaging, 2nd Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China, ³Math and Information Technology, Hanshan Normal University, Guangdong, China, ⁴Provincial Key Laboratory of Medical Molecular Imaging, Guangdong, China

The presence of diabetes increases the risk and severity of stroke, but conventional MRI examinations cannot distinguish between diabetic and non-diabetic stroke. To our knowledge this is the first report on pH-weighted imaging in diabetic stroke models. We obtained a significant pH decrease in the ischemic lesion in diabetes compared with non-diabetes in vivo, which may provide a marker of specificity of diabetic stroke.

Daniel F. Arteaga¹, Manus J. Donahue^1,2, Carlos C. Faraco¹, Taylor L. Davis¹, Jeroen Hendrikse³, Lori C. Jordan², Jeroen C.W. Siero³, Allison O. Scott¹, and Megan K. Strother^1
1Radiology, Vanderbilt University, Nashville, TN, United States, ²Neurology, Vanderbilt University, Nashville, TN, United States, ³University Medical Center Utrecht, Utrecht, Netherlands

We have translated a 7T MRI vessel wall imaging protocol for assessing intracranial vessel wall morphology to a clinically-available 3T MRI sequence without the need for contrast administration. We have performed this protocol on both young, healthy volunteers as well as on patients with moyamoya disease. Our results indicate that it is possible to discern the vessel wall of young, health individuals with our parameters, and that we can reliably identify the major arteries of the Circle of Willis as well as arteries distal to it.

Carlos C. Faraco¹, Manus J. Donahue^1,2, Cari L. Buckingham¹, Fei Ye³, Lori C. Jordan², Daniel F. Arteaga¹, and Megan K. Strother^1
1Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN, United States, ²Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ³Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, United States

Cross cerebellar diaschisis (CCD) is a hypometabolic condition associated with reduced cerebellar blood flow to the hemisphere contralateral to a supratentorial lesion. CCD remains poorly understood partly owing to use of diagnostic modalities not readily available and/or not suitable for longitudinal monitoring, e.g., PET, SPECT, and Gd-MR. The primary aim of this study was to determine whether cerebellar BOLD-weighted cerebrovascular reactivity (CVR) contralateral to supratentorial infarcts correlated with structural and clinical measures of CCD. We demonstrate that BOLD-weighted CVR in the contralateral cerebellar hemisphere correlates with these measures and is a viable, non-invasive alternative to traditional CCD diagnostic imaging modalities.

Jian Hui-Shan^1,2, Chang Ting-Yu¹, Huang Kuo-Lun¹, Chang Yeu-Jhy¹, Chang Chien-Hung¹, Wai Yau-Yau³, Yeh Chih-Hua³, Lee Tsong-Hai¹, and Liu Ho-Ling^4,5
1Department of Neurology and Stroke Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ²Departiment of Biomedical Engineering and Environmental Sciences, Tsing Hua University, Hsinchu, Taiwan, ³Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan,⁴Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ⁵Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States

We investigated whether the impaired cerebrovascular reactivity dynamics in patients with unilateral ICA stenosis is reversible after carotid artery stenting (CAS). Ten subjects underwent dynamic BOLD MRI during repeated breath-holding, before and after stenting, on a 3T scanner. Signal time courses from the MCA territory were extracted for each hemisphere for evaluation. We found that the ipsilateral MCA time course was significantly compromised, presenting as smaller amplitude, wider response and delayed onset, as compared to the contralateral one before CAS (p<0.05). This phenomenon was recovered after CAS, demonstrating significantly improved correlation between BOLD responses obtained from the two hemispheres (p<0.001).

Shalini A. Amukotuwa^1,2, Fernando Calamante², Stephen M. Davis³, Gregory W. Albers⁴, and Roland Bammer^1,5
1Department of Radiology, Stanford University, Stanford, CA, United States, ²The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia, ³Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia, ⁴Department of Neurology, Stanford University, Stanford, CA, United States, ⁵on behalf of the EPITHET, DEFUSE2, and SENSE3 investigators, United States

In acute stroke patients, detection of acute hemorrhage is critical, but must be balanced against the need for fast imaging (as treatment is time-critical). Unfortunately, conventional T2*-weighted gradient-echo (GRE) sequences, the mainstay of hemorrhage detection on MRI, are time consuming. We have investigated and found that DSC-EPI-based PWI has a high sensitivity and specificity for the detection of acute hemorrhage, and hemorrhagic transformation of acute stroke in particular, and is superior to GRE for the detection of intra-arterial thrombus. Therefore, DSC EPI based PWI is likely sufficient for hemorrhage detection, allowing GRE to be omitted from the acute stroke protocol.