Minhui Ouyang¹, Uma Rao², Tejasvi Gundapuneedi¹, and Hao Huang^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Department of Psychiatry and Behavioral Sciences, Meharry Medical College, Nashville, TN, United States

The underlying mechanisms of long-lasting impairments in behavioral, cognitive and social functioning caused by childhood maltreatment (MALTX) are not well-understood. Integrating functional and structural connectivity from resting state fMRI (rs-fMRI) and DTI provides insight of the affected brain circuits including both cortical region and white matter tracts in the maltreated subjects. In this study, rs-fMRI and DTI scanning were acquired from 19 MALTX adolescent volunteers and 13 age-matched control volunteers. We have identified disrupted structural and functional connectivity and revealed the relationship of the abnormal connectivity of both types in the maltreated healthy subjects.

Nikhil Garrepalli¹, Jennifer Robinson², Tracy K. Witte², and Gopikrishna Deshpande^1,2
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, Alabama, United States, ²Department of Psychology, Auburn University, Auburn, Alabama, United States

Men die by suicide more than women in United States, but women are much more likely than men are to make non-fatal suicide attempts. This gender difference in suicide can be explained by interpersonal-psychological theory of suicide. we also delineate the neural mechanisms that are differentially activated in individuals with SB as compared to depression.

Yi Liao¹, Lizhou Chen¹, Xinyu Hu¹, Junmei Hu², Xuanli Chen³, Jianmei Liu², Danlin Shen², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center, Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China, ³Computer Aided Medical Procedures & Augmented Reality, Technische Universität München, Garching bei München, Bayern, Germany

The purpose of this study is to perform a tentative study on schizophrenia patients with severely violence behavior to explore the microstructure abnormalities in the brain. Voxelwise statistical analysis of the FA data was carried out using Tract Based Spatial Statistics. The correlation between extracted FA value in specific regions and WCST, PANSS scores were evaluated for clinical explanations.

Ali-Mohammad Golestani¹, Dolores Malaspina², Laura Miles¹, Nicole Peccerelli¹, and Mariana Lazar^1
1Radiology, Center for Biomedical Imaging, NYU Medical Center, New York, NY, United States, ²Psychiatry, NYU School of Medicine, New York, NY, United States

Visual working memory (VWM) is one of the executive function domains that have been found to be consistently impaired in schizophrenia. Since schizophrenia is modeled as a brain connectivity disorder, we investigated the association between VWM performance and brain anatomical connectivity using Gaussian (fractional anisotropy (FA)) as well as non-Gaussian (mean kurtosis (MK), axonal water fraction (AWF), and tortuosity (Tort)) diffusion parameters in both schizophrenia patients and control subjects. MK and AWF were found to be correlated with VWM in controls, but not in patients. These findings support white matter involvement in VWM poor performance in schizophrenia.

Jeong-Won Jeong^1,2, Jeffrey Kuentzel³, Carla D. Chugani⁴, Harry T. Chugani^2,5, and Diane C. Chugani^2,6
1Pediatrics and Neurology, Wayne State University, Detroit, Michigan, United States, ²PET center, Children's Hospital of Michigan, Detroit, Michigan, United States, ³Psychology, Wayne State University, Detroit, Michigan, United States, ⁴Counseling and Psychological Services, Florida Gulf Coast University, Fort Myers, Florida, United States, ⁵Pediatrics, Neurology, and Radiology, Wayne State University, Detroit, Michigan, United States, ⁶Pediatrics and Radiology, Wayne State University, Detroit, Michigan, United States

Borderline personality disorder (BPD) is a prevalent mental illness characterized by pervasive instability in emotion, interpersonal relationships, self-image, and behavior. Our previous functional MRI study reported atypically modulated Blood Oxygen Level Dependent signals in young adults with BPD, responding to emotionally congruent and incongruent music-face images. This study utilized topologic network analysis for resting state fMRI in order to investigate which brain networks are mostly affected (or functionally impaired) in young adults with BPD, which might provide an objective tool to quantitatively access atypically organized neural mechanism related to BPD phenotypes.

Ivan I. Kirov¹, Caitlin Hardy^1,2, Kant Matsuda³, Graham Wiggins¹, Ajax George¹, Dolores Malaspina², and Oded Gonen^1
1Radiology, New York University, New York, NY, United States, ²Psychiatry, New York University, New York, NY, United States, ³Pathology, New York University, New York, NY, United States

We used 7 T MRI to compare dentate granule cell layer (DGCL) morphology in schizophrenic patients to matched controls’. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from “not discernable” to “easily visible, appearing dark gray or black”). MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings were 3.2±1.0 and 3.5±1.2 in patients versus 3.9±1.1 and 3.8±0.8 in controls. The right DGCL was less discernible in schizophrenia patients compared to controls (p‹0.05), presumably reflecting morphological abnormalities due to cellular organization.

Sean C. L. Deoni¹, Asal Shahidiani², Vera D’Almeida², Steven Williams³, and Declan Murphy^2
1Advanced Baby Imaging Lab, Brown University, Providence, Rhode Island, United States, ²Department of Forensic and Developmental Sciences, King’s College London, London, England, United Kingdom, ³Department of NeuroImaging, King’s College London, London, England, United Kingdom

A recurrent finding in autism spectrum disorder (ASD) is abnormal brain growth, though the neurobiological basis remains unknown. Prior studies have shown slowed micro-structural development in infants with ASD, which may be indicative of myelination differences in children with ASD. Here we cross-sectionally compare myelin development in children and adolescents (6-19 years of age) with ASD and typically developing controls. We show that in brain regions previously implicated in the disorder, children with ASD have increased myelin development (faster growth) in adolescence than typically developing children.

Tae-Hoon Kim¹, Seok-Kwun Kim², Heoung-Keun Kang³, and Gwang-Woo Jeong^1,3
1Research Institute of Medical Imaging, Chonnam National University Medical School, Gwangju, Korea, ²Plastic and Reconstructive Surgery, Donga-A University School of Medicine, Busan, Korea, ³Radiology, Chonnam National University Medical School, Gwangju, Korea

Since sex differentiation of the brain occurs later in development than sex differentiation of genitals, the morphogenesis of the brain plays a critical role in determining gender identity or transsexualism. A few studies investigated the variation of brain structures of male-to-female (MtF) transsexuals. However, no study on the gray matter (GM)-based volume variation of female-to-male (FtM) transsexuals has not yet been studied. This study used a 3 Tesla MRI to compare the volumes of gray matters between FtM transsexuals and female controls using voxel-based morphometry (VBM) analysis.

Lei Wu¹, Vince D. Calhoun¹, Rex Jung², and Arvind Caprihan^1
1The Mind Research Network, Albuquerque, New Mexico, United States, ²Neurosurgery, University of New Mexico, Albuquerque, New Mexico, United States

Whole brain structural connectivity maps based on diffusion imaging data were calculated for a large group of healthy controls and schizophrenia subjects. Connectivity maps were obtained based on probtrackx/FSL algorithm. We develop methods based on group-ICA to parcellate the whole brain into regions characterized by strong connectivity within each region. These regions automatically split the white matter into established white matter tracts and the gray matter into functional modules. This brain parcellation is then used to look for connectivity and the fractional anisotropy differences between HC and SZ groups.

Shaolin Yang^1,2, Olusola Ajilore¹, Minjie Wu¹, Rebecca A. Charlton¹, Melissa Lamar¹, and Anand Kumar^1
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ²Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

Major depressive disorder (MDD) and normal aging both can be accompanied by various changes in the brain. In this report, we examined biophysical integrity of the brain using magnetization transfer ratio (MTR) imaging on 28 patients with MDD and 31 nondepressed controls, aged 30-88 years. While MTR declines with age in the brain regions shared by both groups, such as putamen, the MDD group has additional brain regions showing decline of MTR with age, such as the caudate nucleus. These findings suggest MDD and increasing age in combination are associated with more extensive brain biophysical changes than normal aging alone.

Fabricio R. S. Pereira¹, Marcus V. Zanetti¹, Maurício H. Serpa¹, Tiffany Moukbel Chaim¹, Geraldo Busatto¹, Choukri Mekkaoui², and Marcel Parolin Jackowski^3
1School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil, ²Harvard Medical School, Boston, Massachusetts, United States, ³Computer Science, University of São Paulo, São Paulo, São Paulo, Brazil

Diffusion Tensor MRI provides the fractional anisotropy (FA) and mean diffusivity (MD) indices to characterize the axonal integrity and structure of white matter. Although abnormal levels of FA and MD have been associated with neuropsychiatric conditions, these indices showed to be insufficient to link brain abnormalities to their corresponding clinical symptoms. In this work, we assess the supertoroidal representation of the diffusion tensor by comparing the toroidal volume and toroidal curvature indices to MD and FA in treatment-naïve patients with first-episode psychosis versus healthy controls. TV and TC showed similar findings to MD and FA, but circumscribed to specific areas.

Martin T. Freitag¹, Thomas van Bruggen², Klaus Hermann Fritzsche², Romy Henze³, Romuald Brunner³, Peter Parzer³, Franz Resch³, and Bram Stieltjes^1
1Quantitative Imaging-based Disease Characterization, German Cancer Research Center, Heidelberg, Baden-Wuerttemberg, Germany, ²Division of Medical and Biological Informatics, German Cancer Research Center, Heidelberg, Baden-Wuerttemberg, Germany, ³Department of Child and Adolescent Psychiatry, Section Disorders of Personality Development, University Clinic Heidelberg, Heidelberg, Baden-Wuerttemberg, Germany

Schizophrenia could result from failure of correct lateralization and lead to white matter misconnectivity. Previously, white matter alterations were described in the cerebellum, the visual system and in the corpus callosum. We investigated these regions using TBSS and evaluated potential changes in lateralization of the optic radiation and the superior cerebellar peduncle. A reduction of fractional anisotropy in the whole corpus callosum and the optic radiation and a decreased lateralization of the optic radiation and the superior cerebellar peduncles were observed. Our findings substantiate the concept that schizophrenia is a neurodevelopmental disorder which affects fiber connectivity and white matter lateralization.

Wen-Jang Chu^1,2, Mathew Norris^2,3, Tracie Northern³, Judd Storrs², David E. Fleck^2,3, Elizabeth M. Fugate^1,2, Jing-Huei Lee^2,3, Caleb M. Adler^2,3, Melissa P. DelBello³, Henry Nasrallah³, and Stephen M. Strakowski^2,3
1Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States, ²Center for Imaging Research, Univ. of Cincinnati, Cincinnati, Ohio, United States, ³Psychiatry and Behavioral Neuroscience, Univ. of Cincinnati, Cincinnati, Ohio, United States

This 4-Tesal study investigated the relationships between regional metabolite concentrations and the accuracy of N-back working memory test in healthy subjects and patients with bipolar disorder and schizophrenia.

Mariana Lazar¹, Dolores Malaspina², Laura Miles¹, Ali-mohammad Golestani¹, and Nicole Peccerelli^1
1Department of Radiology, New York University School of Medicine, New York, NY, United States, ²Department of Psychiatry, New York University School of Medicine, New York, NY, United States

DTI literature widely reports reduced fractional anisotropy (FA) in schizophrenia. However, the underlying white matter pathophysiology remains unclear as differences in FA can stem from a variety of causes including differences in myelination and fiber density and geometry. In this study we employed Diffusion Kurtosis Imaging in conjunction with a newly proposed two-compartment white matter diffusion model to evaluate differences in axonal density and myelination in chronic schizophrenia. Our results suggest atypical myelination as a pervasive pathophysiological feature of the disorder. Fiber density does not appear to be significantly affected in this population.

Wen-Jang Chu^1,2, Mathew Norris^2,3, Tracie Northern³, Judd Storrs², David E. Fleck^2,3, Elizabeth M. Fugate^1,2, Jing-Huei Lee^2,3, Caleb M. Adler^2,3, Melissa P. DelBello³, Henry Nasrallah³, and Stephen M. Strakowski^2,3
1Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States, ²Center for Imaging Research, Univ. of Cincinnati, Cincinnati, Ohio, United States, ³Psychiatry and Behavioral Neuroscience, Univ. of Cincinnati, Cincinnati, Ohio, United States

This work investigated the correlations among fMRI, MRS and cognitive task in bipolar, schizophrenic and healthy brains

Yan Li¹, Angela Jakary¹, Erin Gillung², Natalie M. Holbrook², Stuart Eisendrath^2,3, Sarah J. Nelson^1,4, Pratik Mukherjee¹, and Tracy L. Luks^1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²Langley Porter Psychiatric Institute, University of California, San Francisco, California, United States, ³Department of Psychiatry, University of California, San Francisco, California, United States,⁴Department of Bioengineering and therapeutic sciences, University of California, San Francisco, California, United States

The purpose of this study was to compare relative metabolite levels between unmedicated patients with MDD and healthy controls in the anterior cingulate cortex (ACC) and anterior/mediodorsal thalamus (Thal) using 3D short-echo MRSI at 7 Tesla. Compared to controls, patients had significantly decreased levels of GABA/tCr and NAA/tCr in a subregion of the left ACC, significantly elevated tCho/tCr and lower Glu/tCr in the right mediodorsal thalamus, and lower mI/tCr bilaterally in the anterior and mediodorsal thalamus.

Camilo de la Fuente-Sandoval¹, Pablo L. Ortiz², Xiangling Mao³, Patricia Alavarado-Alanis⁴, Oscar Rodríguez-Mayoral⁵, Francisco Reyes-Madrigal⁴, Ariel Graff-Guerrero⁶, Rodolfo Solis-Vivanco⁷, Rafael Favila⁸, and Dikoma C. Shungu^3
1Neuropsychiatry & Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico City, Distrito Federal, Mexico,²Education, INNN, Mexico City, Distrito Federal, Mexico, ³Radiology, Weill Cornell Medical College, New York, NY, United States, ⁴Laboratory of Experimental Psychiatry, INNN, Mexico City, Distrito Federal, Mexico, ⁵Early Psychosis Intervention, Hospital Fray Bernardino Alvarez, Mexico City, Distrito Federal, Mexico,⁶Multimodal Neuroimaging Schizophrenia Group, Centre for Addiction and Mental Health, Toronto, ON, Canada, ⁷Laboratory of Neuropsychology, INNN, Mexico City, Distrito Federal, Mexico, ⁸MR Advanced Applications, GE Healthcare, Mexico City, Distrito Federal, Mexico

In the present study, ¹H MRS was used to investigate potential dysregulations of GABA and glutamatergic compounds in subjects at ultra-high risk (UHR) for schizophrenia compared to healthy controls, and found higher levels of both neurotransmitters in the striatum and medial prefrontal cortex of the UHR group.

Minjie Wu¹, Alexander Kmicikewycz¹, Shaolin Yang¹, Lisa Lu^1,2, Donatello Arienzo¹, and Mani Pavuluri^1
1Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ²Psychology, Roosevelt University, Chicago, IL, United States

Applying graph theory analyses to resting state brain functional data, the present study aims to characterize the system-level changes in brain organization at rest in PBD. Significant increased betweenness centrality in PBD is observed in left amygdala, nucleus accumbens, precuneus, and right temporal pole. PBD also showed significant decreased connectivity degree in left medial OFC, and increased connectivity degree in right DLPFC. The pattern of increased thoroughfare via subcortical nodes of amygdala and nucleus accumbens and altered connectivity strength of DLPFC and OFC offer strong support of how affective and reward circuits are potentially interlinked and impaired in PBD.

Minjie Wu¹, Alexander Kmicikewycz¹, Shaolin Yang¹, Lisa Lu^1,2, Donatello Arienzo¹, and Mani Pavuluri^1
1Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ²Psychology, Roosevelt University, Chicago, IL, United States

In the current study, graph theoretic analyses was applied to diffusion weighted data to explore the topological efficiency of structural networks in pediatric bipolar disorder (PBD). Significantly decreased small-worldness in PBD was observed, which may reflect decreased efficiency in information transfer, and may contribute to the affective and cognitive dysfunction in PBD.

Susanne Bonekamp¹, Richard Anthony Edward Edden¹, Nicolaas A. J. Puts², Jennifer M. Coughlin³, He Zhu^2,4, Mark Varvaris⁵, Nicola Cascella⁶, Akira Sawa³, and Peter B. Barker^1
1Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Radiology, JHU, Baltimore, MD, United States, ³Psychiatry and Behavioral Sciences, JHU, Baltimore, MD, United States, ⁴Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ⁵Neuro Cognitive Neurology, JHU, Baltimore, MD, United States, ⁶Neuropsychiatry, Sheppard Enoch Pratt Hospital, Towson, MD, United States

It has been suggested that oxidative stress plays a role in the pathogenesis of Schizophrenia. This study provides support for the hypothesis that in vivo levels of gluthathione, the major antioxidant in the brain, are altered in the anterior cingulate cortex and dorsolateral prefrontal cortex of patients with Schizophrenia. Further studies are still needed to determine underlying mechanisms, including the effects of treatment, and to investigate the relationship between GSH levels, other markers of oxidative stress, and severity of both positive and negative symptoms.

Camilo de la Fuente-Sandoval¹, Pablo L. Ortiz², Xiangling Mao³, Patricia Alavarado-Alanis⁴, Oscar Rodríguez-Mayoral⁵, Francisco Reyes-Madrigal⁴, Ariel Graff-Guerrero⁶, Rodolfo Solis-Vivanco⁷, Rafael Favila⁸, and Dikoma C. Shungu^3
1Neuropsychiatry & Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico City, Distrito Federal, Mexico,²Education, INNN, Mexico City, Distrito Federal, Mexico, ³Radiology, Weill Cornell Medical College, New York, NY, United States, ⁴Laboratory of Experimental Psychiatry, INNN, Mexico City, Distrito Federal, Mexico, ⁵Early Psychosis Intervention, Hospital Fray Bernardino Alvarez, Mexico City, Distrito Federal, Mexico,⁶Multimodal Neuroimaging Schizophrenia Group, Centre for Addiction and Mental Health, Toronto, ON, Canada, ⁷Laboratory of Neuropsychology, INNN, Mexico City, Distrito Federal, Mexico, ⁸MR Advanced Applications, GE Healthcare, Mexico City, Distrito Federal, Mexico

This study used ¹H MRS to measure and compare brain GABA and glutamatergic compound (Glx) levels in antipsychotic-naïve schizophrenia patients during first-episode psychosis (FEP) and age- and sex-matched healthy control (HC) subjects, and found regional elevations or strong trend-level elevations of both neurotransmitters in the FEP subjects.

Sheeba Arnold Anteraper¹, Susan Whitfield-Gabrieli², Alice Sawyer³, John Gabrieli², and Christina Triantafyllou^4
1A.A. Martinos Imaging Center at McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States, ²Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States, ³Department of Psychology, Boston University, Boston, MA, United States, ⁴A.A. MArtinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

Cerebellar role in Social Anxiety Disorder (SAD) remains yet to be explored using resting state functional connectivity MRI (fcMRI). Here, we are investigating additional neuronal pathways in a patient population with SAD. Compared to healthy controls, we report hyper-connectivity in left amygdala in the medication naïve patient group. Furthermore, significantly stronger temporal correlations revealed between cerebellar seeds and amygdala in the patient group, underscore the involvement of cerebellum in SAD, which could subsequently serve as guidelines for treatment.

Tracy L. Luks¹, Yan Li¹, Angela Jakary¹, Erin Gillung², Natalie M. Holbrook², Stuart Eisendrath², Pratik Mukherjee¹, and Sarah J. Nelson^3
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Langley Porter Psychiatric Institute, San Francisco, CA, United States, ³Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States

We used 7T MRI gradient-echo imaging to examine the thickness of 2 regions within hippocampal CA1, the cell-body layer stratum pyramidale (SP) and the synaptic layer stratum radiatum/stratum lacunosum-moleculare (SRLM) in Major Depressive Disorder patients, and to test the hypothesis that decreases in these ultra-high field MRI measures of hippocampal thickness would be significantly associated with increases in clinical symptom severity and deficits in memory and attention neurocognitive measures known to involve hippocampal function.

Bochao Cheng¹, Xiaoqi Huang¹, Xun Yang², Xinyu Hu¹, Yajing Meng², Shiguang Li¹, Xiuli Wang², and Qiyong Gong^1
1HMRRC.Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan province, China, ²West China Hospital of Sichuan University, Psychiatric department, Chengdu, Sichuan, China

It is the first study to compare the whole-brain based GMV among three anxiety disorders and HC participants. Our results demonstrate that PTSD have siginificant microstructure discrepancy with other three groups. No statastical siginificant difference in GMV can be found between OCD, SAD and HC group. Our finding show that PTSD might have different psychopatholgy circuit with OCD and SAD, which may give new proposal for the upcoming DSM ¨CV and ICD-11.

Yulin Ge¹, Yongxia Zhou², Hanzhang Lu³, Feng Xu³, Ilya Kister⁴, Hina Jaggi², Damon Kenul², Joseph Herbert⁵, and Robert I. Grossman^6
1Radiology, New York University Langone Medical Center, New York, New York, United States, ²Radiology, NYU Medical Center, New York, New York, United States, ³2Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, ⁴Neurology, NYU Medical Center, New York, New York, United States, ⁵Neurology, New York University, New York, New York, United States, ⁶Radiology, New York University, New York, New York, United States

The cerebrovascular reactivity (CVR) may be impaired due to chronic and tonically higher level of nitric oxide (NO) secondary to the repetitive inflammatory activities in patients with multiple sclerosis (MS). This may lead to defective instantaneous oxygen supply to active neurons leading to chronic hypoxia and neurodegeneration. Using mild hypercapnia (mixed 5%CO2, 21%O2, and 74%N2) perfusion MRI at 3T MR, we found significant decrease of average global CVR of gray matter and normal appearing white matter in MS patients using psudo-continuous arterial spin labeling (pCASL) hypercapnia technique. This is the first study to measure CVR abnormalities in MS.

Olivier E. Mougin¹, Rasha Abdel-Fahim², Alain Pitiot³, Nikos Evangelou², and Penelope A. Gowland^4
1SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, Select, United Kingdom, ²Clinical Neurology, School of Clinical Sciences, Faculty of Medicine and Health Sciences, Nottingham, Nottinghamshire, United Kingdom, ³School of Psychology, Nottingham, Nottinghamshire, United Kingdom, ⁴SPMMRC, University of Nottingham, Nottingham, Select, United Kingdom

This study aims to detect pure intra-cortical lesions in MS patients. High resolution Null Point Images, part of the Phase Sensitive Inversion Recovery protocol (0.6mm isotropic), have been acquired at 7T using a novel imaging sequence. The NPI and PSIR contrast has been compared between white matter, grey matter and cortical grey matter, showing a greater NAGM/cGM lesion contrast to noise ratio at 7T for the NPI, providing a better delineation of the WM and the cGM lesions at high resolution. The sequence is being used to study changes in the cortex of MS patients

Yosef A. Berlow¹, Manoj K. Sammi¹, Audrey H. Selzer¹, Dennis Bourdette¹, and William D. Rooney^1
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States

High resolution tissue classification is achievable at high magnetic field strengths by a novel iterative bias field estimation and correction. An innovative approach is illustrated in a Multiple Sclerosis study for brain tissue volume measurements.

Hagen H. Kitzler¹, Hannes Wahl¹, Jason Su², Nora Nilles¹, Henning Schmitz-Peiffer³, Tjalf Ziemssen³, Sean C. L. Deoni⁴, and Brian K. Rutt^2
1Neuroradiology Department, Technische Universitaet, Dresden, SN, Germany, ²Radiology Department, Stanford University, Palo Alto, CA, United States,³Neurology Department, Technische Universitaet, Dresden, SN, Germany, ⁴Engineering Department, Brown University, Providence, RI, United States

Multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) was applied on Clinically Isolated Syndrom (CIS) patients in a longitudinal trial to investigate the potential sensitivity of mcDESPOT-derived measures in detecting early and conventionally invisible disease-related myelin loss. The inter-subject variance of MWF was higher than the scanning intra-subject variance proofing the consistency of repeated measurements. Significantly reduced values of Myelin Water Fraction (MWF) were found in white matter lesions and a correlation between time since symptom onset and the decrease of the Parenchymal Volume Fraction (PVF) was revealed in preliminary baseline scans.

Adrienne N. Dula^1,2, Richard D. Dortch^1,2, David R. Pennell², Francesca Bagnato², Siddharama Pawate³, John C. Gore^1,2, and Seth A. Smith^1,2
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ²Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ³Neurology and Neuroimmunology, Vanderbilt University, Nashville, TN, United States

Diffuse abnormalities in the normal appearing white matter (NAWM) in multiple sclerosis (MS) patients are known to exist in both the brain and spinal cord (SC). The goal of this study was to use MRI contrast due to chemical exchange by saturation transfer (CEST) to measure protein content (APT) in NAWM of the brain and SC in MS subjects compared to healthy controls. The mean APT metrics were significantly different for healthy (2.03±1.14%) and MS subjects (2.91±2.42%), additionally, the MS data exhibits considerable positive skewness (2.49) relative to healthy subjects (0.79) potentially reflective of the diffuse pathophysiology of the NAWM.

Audrey Peiwen Fan¹, Sindhuja Tirumalai Govindarajan², R. Philip Kinkel³, Bruce R. Rosen^2,4, Elfar Adalsteinsson^1,2, and Caterina Mainero^2,4
1Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States, ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁴Harvard Medical School, Boston, MA, United States

This work evaluates the reproducibility of quantitative oxygen extraction fraction (OEF) measurements in adult volunteers and in patients with MS at 7 Tesla. Mean cortical OEF was evaluated from MRI gradient echo phase images in pial vessels parallel to the main field. We observed excellent intra-observer OEF agreement in a cohort of 5 patients and 5 controls, with coefficient of variation (COV) = 2.1%. Scan-rescan reproducibility a week apart in healthy subjects was also acceptable, with COV = 5.9%. This study supports use of quantitative phase-based OEF as a reliable MRI method to assess oxygenation in the brain.

Elisabetta Pagani¹, Maria A. Rocca¹, Paolo Preziosa¹, Sarlota Mesaros², Dusan Damjanovic³, Tatjana Stosic-Opincal³, Jelena Drulovic², and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy,²Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, BG, Yugoslavia, ³Clinic of Radiology, Faculty of Medicine, University of Belgrade, Belgrade, BG, Yugoslavia

Using Tensor Based Morphometry, we investigated the patterns of regional gray matter (GM) and white matter (WM) atrophy and their changes over one year in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We found that WM loss followed a linear evolution from disease onset, while a transient increase of GM volume in a few regions was detectable early in the disease course followed by the development of GM atrophy, thus possibly reflecting structural plasticity to damage.

Caterina Mainero¹, Sindhuja T Govindarajan¹, R. Philip Kinkel², Allen S. Nielsen², and Julien Cohen-Adad^1,3
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ³Department of Electrical Engineering, Institute of Biomedical Engineering, Ecole Polytechnique de Montreal, Montreal, QC, Canada

We combined T2* relaxation decay at 7 Tesla MRI with a surface-based laminar analysis, which allows for selective sampling of T2* at different depths from pial surface across the whole cortex, to investigate in vivo a gradient in the expression of cortical pathology in multiple sclerosis (MS), until now reported at post-mortem only. Our data show that in early MS cortical T2* changes are focal and mainly confined to the iuxtameningeal cortical layers. As MS progresses cortical changes involve deeper cortical laminae, and extend across multiple cortical areas. Future longitudinal studies are needed to confirm these preliminary observations.

Jing Zhang¹ and Alex L. MacKay^1,2
1Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada, ²Department of Physics and Astonomy, University of British Columbia, Vancouver, British Columbia, Canada

2. Myelin water fractions (MWF) estimated by mcDESPOT method are significantly higher than MWF values derived from multi-spin echo T2-decay curve approachs. It has been suggested that magnetization transfer (MT) may influence the MWF maps. We performed the mcDESPOT method with both short and longer RF pulses in order to investigate effect of MT on the MWF maps. We conclude that the MT effects did play a role in the estimated MWF from mcDESPOT. This effect was more marked in grey matter but less marked in white matter.

Wan Hazlin Zaini¹, Zhang Chen¹, Min Liu¹, Fabrizio Giuliani², Chris Hanstock¹, and Christian Beaulieu^1
1Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada, ²Division of Neurology, University of Alberta, Edmonton, Alberta, Canada

Conventional magnetic resonance imaging has low ability to predict disease progression in multiple sclerosis patients. We used diffusion tensor brain network analysis to assess differences among early relapsing-remitting MS patients with low disability and various levels of lesion load. Relative to controls, the high lesion load group, but not the low lesion load group, had reduced global and local network efficiency and increased shortest path length that all correlated with lesion load within that group. Diffusion tensor brain network analysis identifies altered white matter network properties that may provide a potential biomarker of disease progression.

Paola Valsasina¹, Maria A. Rocca¹, Gianna Riccitelli¹, Claudio Gobbi^1,2, Elisabetta Pagani¹, Paolo Preziosa¹, Vittorio Martinelli³, Giancarlo Comi³, and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy,²Department of Neurology, Neurocentre of Southern Switzerland, Lugano, TI, Switzerland, ³Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy

We investigated whether depression in 123 multiple sclerosis (MS) is related to specific pattern of lesion distribution and gray matter (GM) and white matter regional atrophy and their modulation by presence of fatigue. A positive interaction was detected between depression and fatigue at the level of the right superior frontal gyrus (SFG). Depression had a selective effect on atrophy of the left precentral gyrus and right inferior frontal gyrus. Depression in MS is linked to GM atrophy of regions located in the bilateral frontal lobes. The concomitant presence of depression and fatigue is associated to atrophy of the right SFG.

Ying Wu^1,2, Huan Tan¹, Ryan Hutten¹, Tian Liu³, Hongyan Du^1,4, Hector Ferral^1,2, Matthew Walker^1,2, Joel Meyer^1,2, Yi Wang³, and Robert R. Edelman^1,5
1Department of Radiology, NorthShore University HealthSystem, Evanston, IL, United States, ²Department of Radiology, The University of Chicago Pritzker School of Medicine, Chicago, IL, United States, ³Weill Cornell Medical College, New York, New York, United States, ⁴Center for Clinical and Research Informatics (CCRI), NorthShore University HealthSystem, Evanston, IL, United States, ⁵Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Pathohistological and MR studies indicate possible iron accumulation in MS brain. Compared to previous iron susceptibility quantification methods, quantitative susceptibility mapping (QSM) is potentially more robust and more intrinsic to iron induced susceptibility. In this study, we performed QSM in MS patients to characterize lesion burden, and demonstrate the potential of QSM as a new sensitive clinical strategy for MS lesion identification, as well as a quantitative imaging marker for monitoring disease progression and/or responses to treatments. Conclusions: Our results provide preliminary evidence that the QSM holds promise for assessing iron change in MS brain and may add to clinical lesion visualization.

Vasily L. Yarnykh¹, James D. Bowen², Alexey A. Samsonov³, Pavle Repovic², Angeli Mayadev², Bart P. Keogh², Beena Gangadharan², Hunter R. Underhill¹, Kenneth R. Maravilla¹, and Lily K. Jung Henson^2
1Radiology, University of Washington, Seattle, WA, United States, ²Swedish Medical Center, Seattle, WA, United States, ³Radiology, University of Wisconsin, Madison, WI, United States

Macromolecular proton fraction (MPF) is a key biophysical parameter determining magnetization transfer (MT) between water and macromolecules in tissues and a promising biomarker of demyelination in multiple sclerosis (MS). In this study, MPF measured in white matter, gray mater, and MS lesions was directly compared to more traditional quantitative MRI parameters, such as MT ratio (MTR), R1, and lesion volume on a population of MS patients. The results demonstrate the superiority of MPF in both discrimination of pathologic brain tissue changes and correlations with disability compared to the above quantitative MRI parameters.

Guillaume Bonnier¹, Tilman Johannes Sumpf², David Romanasco¹, Alexis Roche¹, Myriam Schluep³, Renaud Du Pasquier³, Jens Frahm², Gunnar Krueger⁴, and Cristina Granziera^3
1ACIT, EPFL, Lausanne, Switzerland, ²biophysikalische Chemie · Biomedizinische NMR Forschungs GmbH, Max Planck Institute, Göttingen, Germany, ³Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, ⁴Advanced Clinical Imaging Technology, Siemens Healthcare IM S AW, Lausanne, Switzerland

In this study, we investigated the sensitivity of ultrafast T2 relaxometry measurements (ca 3 min acquisition time for the whole brain) in early stages of multiple sclerosis. We extracted regions of interest (ROIs) using a software based on variational expectation-maximization tissue classification; we then performed a statistical analysis using permutation-based Hotelling tests, using age and gender as covariates and correction for family-wise error rate. Results show that white matter T2 values were significantly higher in patients than in controls, suggesting that ultrafast T2 sequence provides a valuable instrument to quantify the impact of MS in early stages of the disease.

Tejasvi Gundapuneedi¹, Hao Huang¹, Nicholas Hubbard², Joanna Hutchison², and Bart Rypma^2
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Center for Brain Health, University of Texas at Dallas, Richardson, TX, United States

Diffusion Tensor Imaging (DTI) is capable of quantifying white-matter (WM) microstructural changes of patients with neurological diseases such as Multiple Sclerosis (MS). The WM can be generally categorized into four tract groups, commissural, limbic, association and projection tracts, based on their functions. Whereas extensive previous work has documented MS-related WM changes, there has been minimal work investigating the functional consequences of these changes. In this study we assessed the sensitivity of the multiple DTI-derived metrics in these four tract groups to MS WM pathology and performance changes, assessed by neuropsychological measures.

Ashish Raj¹, XIaobo Shen², Thanh D. Nguyen, PhD³, and Susan A. Gauthier^4
1Department of Radiology, Weill Cornell Medical Collge, New York, NY, United States, ²Department of Computer Science, Cornell University, Ithaca, NY, United States, ³Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ⁴Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY, United States

To introduce a new post-processing technique for quantifying myelin in the brain, with specific application to the examination of demyelinating disesaes like Multiple Sclerosis. T2 Relaxometry is a popular MRI technique which can separate the contribution of various tissue components in the brain, thereby quantifying the myelin content of brain regions. It works by capturing several MRI scans at different echo times, followed by a numerical fitting procedure to fit multiple components exponentially relaxing at different T2 time constants. Unfortunately, the post-processing required to obtain myelin maps from T2 data is a hard numerical problem due to ill-posedness of the problem. Consequently, the T2 distributions and the resulting myelin water fraction (MWF) maps become very sensitive to noise and are frequently difficult to interpret diagnostically. Hence T2 relaxometry typically necessitates very high SNR T2 scans which can take several hours for whole brain coverage – clearly a clinically unfeasible proposition. Here, we propose a new way of solving the inverse problem in T2 relaxometry by imposing spatial smoothness constraints and by restricting the relaxing T2 distribution to 2 Gaussian-shaped peaks corresponding to myelin water and intra/extra-cellular water. The method greatly improves robustness to noise, reduces spatial variations and definition of white matter fiber bundles in the brain. This allows it to be used on fast but low-SNR spiral acquisitions which take only 10 minutes for whole brain coverage.

Michael Amann¹, Michaela Andelova², Athina Papadopoulou^2,3, Yvonne Naegelin², Julia Reinhardt⁴, Katrin Weier², Ernst-Wilhelm Radue³, Ludwig Kappos², Oliver Bieri⁵, Christoph Stippich⁴, and Till Sprenger^1
1Neurology/Neuroradiology, Universitätsspital Basel, Basel, BS, Switzerland, ²Neurology, Universitätsspital Basel, Basel, BS, Switzerland, ³Medical Image Analysis Centre, Basel, BS, Switzerland, ⁴Neuroradiology, Universitätsspital Basel, Basel, BS, Switzerland, ⁵Medical Physics, University of Basel Hospital, Basel, BS, Switzerland

In this study, we measured the brain's magnetisation transfer ratio (MTR) in 75 multiple sclerosis patients with balanced steady-state free precession (bSSFP). The study protocol included a 3D DIR sequence, a volumetric 3D-T1w scan and the 3D bSSFP MTR sequence. The T1w volumes were segmented into grey matter, white matter and CSF, also subcortical segmentation was performed. Normal appearing white matter had highest and nucleus accumbens had lowest MTR, both differed significantly from all other structures. The MTR of the thalamus was also significant different from all other structures, and it was closer to white matter MTR than to the MTR of cortex.

Milos Ivkovic¹ and Susan A. Gauthier^1
1Weill Cornell Medical College, New York, New York, United States

It has been noticed that DTI metrics on certain white matter tracts, such as optic radiation, correlate better with MS physical disability scores than other WM tracts, in particular corticospinal tract. We compared correlation between EDSS and DTI metrics obtained by two different methods: (1) Region-of-Interest based method and (2) recently developed tractography method where neuronal tracts are reconstructed directly on patient data. Further, we investigated age related differences in EDSS and DTI metrics and used 3 longitudinal EDSS scores on the same cohort of patients, which lead us to propose that observed differences in correlation with physical disability occur because changes in certain tracts are due to primary MS pathology, while observed differences in other tracts are mostly due to atrophic degeneration.

Eve LoCastro¹, Sneha N. Pandya¹, Xiobo Shen², Thanh Nguyen, PhD¹, Susan A. Gauthier³, and Ashish Raj^1
1Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ²Department of Computer Science, Cornell University, Ithaca, NY, United States, ³Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY, United States

To introduce a new software pipeline for performing clinically feasible and routine quantitative myelin imaging via T2 Relaxometry, with specific application to demyelinating diseases like Multiple Sclerosis. T2 Relaxometry uses multi-echo T2weighted images to separate the contribution of various tissue components in the brain, thereby quantifying the myelin content. We have developed a fully automated pipeline in MATLAB featuring 3 steps: a) fast 3D T2-prepared spiral MR sequence for rapid multi-echo T2 imaging, b) a new post-processing technique obtaining T2 distributions and myelin fractions, and c) fully automated atlas-based coregistration, segmentation and parcellation pipeline to enable cross-subject voxel-based analysis. The overall pipeline is depicted in Fig 1. This analysis pipeline will be made publically available to facilitate routine myelin imaging and statistical analysis in common space.

Yuxiang Zhou^1,2, Lingyun Chen², Xiaojun Sun¹, Sushmita Datta³, Jerry S. Wolinsky⁴, and Ponnada A. Narayana^1
1Department of Diagnostic and Interventional Imaging, University of Texas Medical School at Houston, Houston, TX, United States, ²Department of Diagnostic Radiology & Molecular Imaging, Beaumont Health System, Royal Oak, MI, United States, ³Department of Diagnostic and Interventional Imaging, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States, ⁴Department of Neurology, University of Texas Medical School at Houston, Houston, TX, United States

MRI based pCASL was used to quantify cerebral blood flow (CBF) for determining the regional CBF deficits in multiple sclerosis (MS) patients relative to controls in multiple brain regions. The results suggested significant regional perfusion reduction in MS patients. The lowest CBF value in WM mainly corresponds to central WM, the area where chronic MS lesions appear with high probability. The persistence of chronic lesions in poorly perfused WM strongly implicates hypoperfusion as an important factor that interferes with lesion repair.

Yong Wang¹, Peng Sun¹, Anne H. Cross^2,3, and Sheng-Kwei Song^1,3
1Radiology, Washington University in St. Louis, Saint Louis, MO, United States, ²Neurology, Washington University in St. Louis, Saint Louis, MO, United States, ³Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, United States

Gaining a full understanding of the pathogenesis of multiple sclerosis (MS) requires longitudinal studies, which presents a special challenge because the acquisition of tissue samples has the potential of causing harm to patients. Recently developed diffusion basis spectrum imaging (DBSI) can simultaneously quantify axonal injury, demyelination, and inflammation in the CNS disease, therefore holds promise of conducting longitudinal studies which noninvasively reveal the changing histopathology of MS lesions. In this study, we first examined the reproducibility of repeated clinical DBSI scans on selected image voxels from healthy volunteers. Following the reproducibility study, an MS patient was scanned 4 times following the initial diagnosis and during treatment. Preliminary data indicated that DBSI could follow the pathological substrate changes occurring with time and treatment, and potentially be used to eveluate the effectiveness of different treatment protocols.

Jing Zhang¹ and Alex L. MacKay^1,2
1Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada, ²Department of Physics and Astonomy, University of British Columbia, Vancouver, British Columbia, Canada

mcDESPOT derives two-component relaxation information from spoiled and fully balanced steady-state (SPGR and bSSFP) imaging data acquired over multiple flip angles. However, the two water-pool model may be inadequate to address the complex nature of water pools in brain. We analyzed mcDESPOT data using a T2 relaxation model with an arbitrary number of components. The results show that a two pool model may be unable to describe the complex water environments found in brain. MWF values obtained from the T2 distribution of mcDESPOT were smaller and closer to values obtained from the literature.

Yong Wang¹, Peng Sun², Fang-Chang Yeh³, Robert Naismith^4,5, Anne H. Cross^4,5, and Sheng-Kwei Song^1,6
1Radiology, Washington University in St. Louis, Saint Louis, MO, United States, ²Radiology, Washington University in St. Louis, St. Louis, MO, United States,³2Departments of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States, ⁴Neurology, Washington University in St. Louis, Saint Louis, MO, United States, ⁵Hope Center of Neurological disorders, Washington University in St. Louis, St. Louis, MO, United States, ⁶Hope Center of Neurological disorders, Washington University, St. Louis, MO, United States

Conventional magnetic resonance imaging (MRI) has limited capability to detect and quantify the severity and evolution of inflammation, axonal injury and demyelination, coexisting in multiple sclerosis (MS). Recently developed diffusion basis spectrum imaging (DBSI) has demonstrated promise to address these limitations in animal studies. However, DBSI translation to MS patients has not been conducted. In this study, eight healthy volunteers and eight age gender matched MS patients underwent DBSI scans. We report that DBSI-biomarkers were able to reveal detailed pathological profiles within lesions that missed by conventional MRI and DTI.

Keith R. Thulborn¹, Ian C. Atkinson¹, Aiming Lu¹, Saad Jamil¹, Wesley McClain¹, Matthew Koshy¹, Pauliah Mohan², Kathryn Beal², Antonio M. Omuro², and Michelle Bradbury^2
1Ctr Magnetic Resonance Research, University of Illinois, Chicago, IL, United States, ²Radiology, Memorial Sloan Kettering Cancer Ctr, New York, NY, United States

Quantitative sodium MR imaging and the two-compartment model of tissue sodium concentration have been used to measure weekly and accumulated changes in tissue cell fraction (TCF) of human high grade brain tumors during fractionated radiation therapy. Whereas some tumors show regionally distinct responses within weekly intervals, others show no response. This near real-time capability of early monitoring of tumor responsiveness to treatment could be used to guide adaptive therapy or to switch to more effective alternative therapy. The lack of responsiveness in many of these tumors explains why the prognosis remains so grime for these aggressive tumors.

Monika Huhndorf¹, Christian Stehning², Axel Rohr¹, Michael Helle³, Ulrich Katscher², and Olav Jansen^1
1Institute of Neuroradiology, University Medical Center Schleswig-Holstein, Kiel, Germany, ²Philips Research Europe, Hamburg, Germany, ³Philips Research Laboratories, Hamburg, Germany

With Electric Properties Tomography (EPT), we are able to measure the electric conductivity of tissue as an additional parameter, which might improve the diagnostic of brain tumors and other diseases using standard MRI-sequences. Previous single case studies showed different conductivity for grey and white matter as well as for malignant and healthy brain tissue. In this study, we systematically examined 12 patients with intracerebral tumors in reference to the electrical conductivity of the tissue using a dedicated EPT sequence and reconstruction optimized for brain studies.

Liya Wang^1,2, Tricia King³, and Hui Mao^1,2
1Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, ²Center for Systems Imaging, Emory University, Atlanta, GA, United States, ³Department of Psychology, Georgia State University, Atlanta, GA, United States

Radiotherapy causes treatment-related white matter (WM) integrity changes and potential functional impairments. While predicting short-term outcomes (less 5 years) has been investigated, factors affecting predicting longer term (over 10 years) outcomes have not been understood. This study aimed for quantitative evaluation of WM microstructure damages using diffusion tensor imaging and determining correlation of such damage with long-term brain function restrictions in adult survivors of childhood brain tumors so that we can better understand the progression of microstructure damage underlying the brain functioning decline by recognizing complications of radiotherapy. It can lead to optimize radiotherapy techniques to minimize collateral brain damage.

Alexander Brost¹, Neilesh Gupta¹, Christoph Seeger^1,2, Aaryani Tipirneni¹, Zhaoying Han¹, Sjoerd B. Vos^1,3, Julian R. Maclaren¹, Matus Straka¹, Nancy J. Fischbein¹, and Roland Bammer^1
1Center for Quantitative Neuroimaging, Stanford University, Stanford, CA, United States, ²Pattern Recognition Lab, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, ³Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

The assessment of brain tumor progression or regression is an important task in neuroradiology. To standardize review, baseline 3D MRI brain scans were first registered to an atlas and kept in a research PACS system (RAPID). When patients presented for follow-up studies, these were registered to the baseline data set and displayed next to each. Comparison of tumor behavior between the two scans was also more accurate and interpreted with higher confidence. Automatic registration of 3D data for image alignment on serial studies offers a faster and more accurate assessment of changes in tumor size than the standard clinical assessment.

Masami Yoneyama¹, Masanobu Nakamura¹, Taro Takahara², Thomas C. Kwee³, Atsushi Takemura⁴, Makoto Obara⁴, Takashi Tabuchi¹, and Satoshi Tatsuno^1
1Yaesu Clinic, Tokyo, Japan, ²Tokai University School of Engineering, Kanagawa, Japan, ³University Medical Center Utrecht, Utrecht, Netherlands, ⁴Philips Electronics Japan, Tokyo, Japan

Contrast-enhanced (CE)-MRI, using a 3D T1W GRE sequence, is an established method for screening of brain metastasis. However, since contrast materials remain in both blood and the tumor parenchyma, differentiation of vessels and tumor may become difficult. For overcoming this problem, 3D MSDE-TSE has come into use recently. Although MSDE-TSE can produce excellent-quality black-blood images in CE studies, it may suffer from decreasing of T1 contrast. To improve the T1 contrast of 3D MSDE-TSE sequences, we focused on the anti driven equilibrium (ADE). In this study, we propose a T1-enhanced whole-brain black-blood RARE imaging, using MSDE-TSE with ADE, for CE brain tumor screening, and to compare with the conventional methods.

Günther Grabner¹, Sabine Goed¹, Adelheid Wöhrer², Christine Marosi², Aygül Mert³, Stefan Wolfsberger³, Georg Widhalm³, Siegfried Trattnig¹, and Matthias Preusser^2
1Department of Radiology, Medical University of Vienna, Vienna, Austria, ²Institute of Neurology, Medical University of Vienna, Vienna, Austria,³Department of Neurosurgery, Medical University of Vienna, Vienna, Austria

This study shows that the local image variance based on Susceptibility-Weighted Imaging (SWI) at 7 Tesla can facilitate the differentiation between glial tumors. It is also shown that the local image variance correlates with histopathological findings.

Benjamin M. Ellingson^1,2, Timothy F. Cloughesy³, Robert J. Harris¹, Davis C. Woodworth¹, Kevin Leu¹, Albert Lai³, Phioanh (Leia) Nghiemphu³, and Whitney B. Pope^1
1Dept. of Radiological Sciences, UCLA, Los Angeles, CA, United States, ²Biomedical Physics, UCLA, Los Angeles, CA, United States, ³Neurology, UCLA, Los Angeles, CA, United States

Expert radiologists and neuro-oncologists can identify subtle growth in the tumor through visual examination of the mass effect on serial MR scans; however, these evaluations are subjective and are not quantitative. The current study involves the development of a new class of imaging biomarkers that quantify parameters associated tissue deformation fields derived from serial nonlinear (elastic) registration of high-resolution post-contrast T1-weighted images in patients with glioblastoma. “Tissue Expansion Maps” (TEMs) that quantify the local tissue displacement velocity and local distortion vector field maps were can be used to detect new tumor invasion and understand patterns in tumor growth and infiltration.

Sumei Wang¹, Sanjeev Chawla¹, Sungheon Kim², Arati Desai³, Michelle Alonso-Basanta⁴, Maria Martinez-Lage⁵, Steven Brem⁶, Elias R. Melhem^1,7, and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, New York University School of Medicine, New York, NY, United States,³Hematology-Oncology, University of Pennsylvania, Philadelphia, PA, United States, ⁴Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States, ⁵Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States, ⁶Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁷Radiology, University of Maryland, Baltimore, MD, United States

The purpose of this study was to determine whether diffusion and perfusion MRI can help in differentiating pseudoprogression (PsP) from true progression (TP) in glioblastoma patients demonstrating enhancing lesions within six months post chemo-radiation therapy. Six patients with PsP and 7 patients with TP underwent DTI and DSC-MRI studies. Significantly elevated median mean diffusivity (MD) and decreased rCBV from the enhancing part of the tumor was observed in patients with PsP compared with TP, indicating that DTI and DSC may be helpful in differentiating PsP from TP.

Xiang Liu¹, Wei Tian¹, Henry Wang¹, and Sven Ekholm^1
1Imaging Science, University of Rochester Medical Center, Rochester, NY, United States

Standard chemo-radiation therapy with temozolomide may induce pseudo-progression in 20-50% patients with glioblastomas, which resembles true tumor progression on conventional MRI. We reviewed sequential MRI examinations in 41 patients with new diagnosed glioblastoma, our preliminary result showed that increased rCBV value in the early post-operative PWI examinations may be useful in differentiating pseudoprogression and tumor progression in such patients within 6 months after radiation/ temozolomide treatment. Early post-operative restricted diffusion has limited potential value in distinguishing pseudo-progression from tumor progression

Tatsuya Yamamoto¹, Hiroaki Takeuchi², Yasuhiro Fujiwara³, and Hirohiko Kimura^1
1Department of Radiology, University of Fukui, Fukui, Japan, ²Department of neurosurgery, University of Fukui, Fukui, Japan, ³Division of Radiography, University of Fukui Hospital, Fukui, Japan

No reports have focused on the evaluation of tumor blood flow (TBF) at the skull base. However, we demonstrated a significant difference in TBF between a skull base meningioma and schwannoma. The significant correlation between %TBF and the tumor vessel luminal area (p < 0.01, r_s = 0.83) suggests that precise evaluation of the tumor perfusion state could be accomplished using pulsed-continuous arterial spin labeling. Thus, differential diagnosis of a skull base tumor may be possible to some extent even without the use of contrast material.

Peter S. LaViolette¹, Mitchell Daun², Melissa A. Prah¹, Kourosh Jafari-Khouzani³, Pavlina Polaskova³, Elizabeth R. Gerstner⁴, Steven M. Stufflebeam³, and Kathleen M. Schmainda^1
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Radiology, Massachusetts General Hospital, Charlestown, MA, United States, ⁴Neurology, Massachusetts General Hospital, Boston, MA, United States

Independent component analysis applied to DSC perfusion data separates arterial and venous voxels based on the temporal dynamics of contrast agent perfusion. This study varies the number of ICA components modeled to determine which number generates the most repeatable arterial and venous maps in 31 patients who underwent two identical DSC imaging sessions days apart. We compare the repeatability of the resulting arterial and venous maps both across different numbers of components modeled, and between the simultaneously acquired spin-echo and gradient-echo acquisitions. We find that modeling 3 components results in highly repeatable arterial and venous maps, and that ICA maps generated from GE data are more repeatable than SE.

Jalal B. Andre¹, Seema Nagpal², Daniel S. Hippe¹, Heiko Schmiedeskamp³, Roland Bammer³, Reena Thomas², Matus Straka³, Lawrence Recht², and Greg Zaharchuk^3
1Radiology, University of Washington, Seattle, Washington, United States, ²Neuro-oncology, Stanford University, Stanford, California, United States,³Radiology, Stanford University, Stanford, California, United States

The anti-tumoral effects of bevacizumab have been well documented in glioblastoma multiforme, and is attributable in part to it's anti-angiogenic properties. Little attention has been given to the potential alteration in global cerebral blood flow that might results from administration of this therapeutic agent, which is examined in this research.

Masaki Katsura¹, Masaaki Hori², Issei Fukunaga³, Fumitaka Kumagai³, Hiroki Sasaki¹, Harushi Mori¹, Akira Kunimatsu¹, Yoshitaka Masutani¹, Keigo Shimoji², Atsushi Nakanishi², Shigeki Aoki², and Kuni Ohtomo^1
1Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, ²Radiology, School of Medicine, Juntendo University, Tokyo, Japan,³Graduate School of Health Promotion Science, Tokyo Metropolitan University, Tokyo, Japan

In the current study on clinical cases with glioblastoma, we performed diffusion kurtosis imaging (DKI) fitting analyses by applying different combination of b-values. It is crucial that an appropriate b-value combination be independently established for pathologic brain tissue before applying DKI to clinical practice.

Yan Bai¹, Meiyun Wang¹, Dapeng Shi¹, and Jinyuan Zhou^2
1Radiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China, ²Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Diffusion-weighted MR imaging as a noninvasive technology sensitive to microscopic water diffusion has been one of the hottest tools used in neurological diseases in recent years. Previous studies commonly used quantitative ADC obtained from monoexponential fit to grade gliomas. However, the ADC calculated by monoexponential model was influenced by microcirculation of blood in vivo. The separation of diffution and perfusion was obtained from intravoxel incoherent motion (IVIM) imaging of biexponential analysis with multiple b values. A stretched-exponential model of diffusion reflect the intravoxel heterogeneity in the distribution of diffusion coefficientsl.Our study investigated the comparison of monoexponential, biexponential and stretched-exponential models of DWI in grading gliomas.

Jinsoo Uh¹, Chia-ho Hua¹, Michael Lam², Daniel J. Indelicato³, and Thomas E. Merchant^1
1Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, United States, ²Chemistry and Physics, Union University, Jackson, TN, United States, ³Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, FL, United States

Alteration of normal-appearing white matter tissues induced by proton therapy to craniopharyngioma has been assessed by DTI. We observed reduction of FA and increase of RD at 3 months after proton therapy in all regions of interest analyzed in this study. This result implied compromised structural integrity of white matter contributed by demyelination. However, it appeared that these changes are relatively mild compared to those previously reported based on photon therapy, and the data from 6 month follow-up suggested that the alteration has recovered. Longer follow-up with a larger number of patients will be helpful to confirm this observation.

Andrew A. Maudsley¹, Bhaswati Roy², Rakesh K. Gupta², Sulaiman Sheriff¹, Rishi Awasthi², Meng Gu³, Nuzhat Hussain⁴, Sudipta Mohakud², Sanjay Behari², and Daniel Spielman^3
1Radiology, University of Miami, Miami, FL, United States, ²Radiodiagnostics, SGPGIMS, Lucknow, Uttar Pradesh, India, ³Radiology, Stanford University, Stanford, CA, United States, ⁴Pathology, Ram Manohar Lohia, Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

This study reports changes of tissue metabolism, determined using 1H 3D MRSI, and ADC in tissue regions that are remote from the lesion and appear normal on conventional MRI for subjects with glioma. The associations of these changes with tumor grade are reported.

Sumei Wang¹, Sang Joon Kim^1,2, John H. Woo¹, Suyash Mohan¹, Ruyun Jin³, Matthew R. Voluck¹, Ronald L. Wolf¹, Donald M. O’Rourke⁴, Harish Poptani¹, Elias R. Melhem^1,5, and Sungheon Kim^6
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Ulsan Asan Medical Center, Seoul, Korea, ³Medical Data Research Center, Providence Health & Services, Portland, Oregon, United States, ⁴Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁵Radiology, University of Maryland, Baltimore, MD, United States, ⁶Radiology, New York University School of Medicine, New York, NY, United States

In this study, we investigated the potential of DTI metrics for differentiation tumor types with a substantially larger cohort (n = 222) and also its performance in comparison with two experienced neuroradiologists. 128 glioblastomas and 94 brain metastases were included in this study. Two neuroradiologists independently reviewed the images. Diagnostic performance was evaluated using ROC curve for the two raters and logistic regression model (LRM). Our result indicates that our model is as good as experienced neuroradiologist. Furthermore, it was found that the accuracy of LRM model did not vary as much as those of the raters depending on the selection of the cases.

Douglas A.C. Kelley¹, Suchandrima Banerjee², Wei Bian³, Julia P. Owen⁴, Christopher P. Hess⁴, and Sarah J. Nelson^4
1Applied Science Laboratory, GE Healthcare, Corte Madera, CA, United States, ²Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States,³Radiology, UC San Francisco, San Francisco, CA, United States, ⁴Radiology, UCSF, San Francisco, CA, United States

While 7T provides significant improvements in image quality for many techniques for characterizing human brain tumors, diffusion is generally of poorer quality due to the effects of B0 and B1 inhomogeneity, generally requiring a 3T study as well. Advances in parallel imaging, multiband excitation, and B1 mapping have allowed significant improvements leading to diffusion images of comparable quality to 3T without requiring specialized gradient systems. Data from a representative patient are presented and compared to 3T.

Qiuting Wen^1,2, Adam Elkhaled², Emma Essock-Burns¹, Annette Molinaro³, Joanna Phillips^3,4, Susan M. Chang⁵, Soonmee Cha⁶, and Sarah J. Nelson^1,7
1Graduate Group in Bioengineering, UC Berkeley/UC San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, UC San Francisco, San Francisco, CA, United States, ³Department of Neurological Surgery, UC San Francisco, San Francisco, CA, United States,⁴Department of Pathology, UC San Francisco, UCSF San Francisco, CA, United States, ⁵Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, ⁶Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States, ⁷Bioengineering and Therapeutic Science, UC San Francisco, San Francisco, CA, United States

Treatment with radiation and chemotherapy may result in gliosis, edema and necrosis, which can mimic tumor recurrence in standard MR images. Differentiating between these effects is a critical central challenge in neuro-oncology [1]. Acquisition of image guided tissue samples can enable the association of pathological properties of the tissue with pre-surgical MR parameters [2]. Ex vivo spectroscopy also offers direct association of pathology with a wide range of cellular metabolites [3]. The purpose of this study was to evaluate which in vivo and ex vivo MR parameters were able to distinguish between tumor and treatment effect in for patients with GBM. Our results showed the ability of PH, in vivo NAA, ex vivo NAA and Cr in differentiating tumor recurrence from treatment effect, which is consistent with the clinical findings that tumor recurrence has elevated angiogenesis and causes more neuronal disruption..It should be noted that there is overlap between the two groups for these parameters (see Figure 2), which suggests that future studies should consider using a multi-variate index to map out regions of recurrent tumor.

Christopher H. Chapman¹, Mohammad Nazem-Zadeh¹, Oliver Lee², Matthew Schipper¹, Christina I. Tsien¹, Theodore S. Lawrence¹, and Yue Cao^1,3
1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States, ²Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States, ³Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States

We examined regional variation in DTI changes following chemoradiotherapy. The largest fractional anisotropy decreases were seen in the cingula, fornix, and corpus callosum. This pattern of selective white matter degradation may be related to specific neurocognitive impairments commonly seen following treatment. Radial and axial diffusivity changes were temporally and spatially separated, supporting their use as specific markers of distinct pathological processes.

Ulrich Pilatus¹, Oliver Bär², Johannes Rieger², Stefanie Pellikan¹, Maurice Harth¹, Joachim Steinbach², and Elke Hattingen^1
1Institute of Neuroradiology, Goethe-University Frankfurt, Frankfurt, Germany, ²Dr. Senckenbergisches Institut für Neuroonkologie, Goethe-University Frankfurt, Frankfurt, Germany

31P and 1H MRSI was used to monitor changes in phospholipid and energy metabolism in recurrent gliomas during antiangiogenic therapy. Elevated PEth/GPE ratios were typical for all recurrent gliomas while high PCho/GPC ratios correlated with the survival time. Both anabolite/katabolite ratios decreased upon onset of therapy. Energy metabolism, mesures as PCr/Pi ratio, was deprived in tumor tissue.

Changho Choi¹, Sandeep Ganji², Akshay Madan¹, Robert Bachoo¹, Ralph DeBerardinis¹, and Elizabeth A. Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²UT Southwestern Medical Center, Dallas, Texas, United States

Citrate (Cit) is positioned at a crucial metabolic branch point, serving as an intermediate both for energy generation and for biosynthesis of lipids and related molecules. Noninvasive analysis of citrate levels in tumors would therefore provide information about these pathways. We are reporting abnormal Cit levels in gliomas in adult patients for the first time. For 89 adult patients with gliomas, Cit was detected in 62 patients, the incidence of Cit elevation in gliomas being 70%. The estimated concentrations ranged from 1 to 4.4 mM (mean¡¾SD = 2.2¡¾0.7 mM), with CRLBs between 6 and 19% (mean¡¾SD = 11¡¾3).

Jie Deng^1,2, Delilah Burrowes¹, and Emma Boylan^1
1Medical Imaging, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, United States, ²Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

This pilot study was to evaluated the anomalous diffusion model and bi-exponential two-compartment model using extended b-value (0-3500 s/mm²) DWI, in differentiation of malignant and benign tumors in pediatric patients. Multiple diffusion parameters including space constant , complex parameter , extracellular diffusion coefficient (D_fast) and volume (V_fast) and intracellular diffusion coefficient (D_slow) and volume (V_slow) were derived from these two models. This study shows a strong correlation in differentiating malignant and benign brain tumor types using simultaneous evaluation of multiple diffusion parameters. This method may prove to be useful in improving the accuracy and confidence in the diagnosis of various brain tumors,

Craig K. Jones^1,2, Domenico Zacà³, Jun Hua^1,2, Jinyuan Zhou^1,2, Peter C.M. van Zijl^1,2, and Jay J. Pillai^4
1Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²FM Kirby Center, Kennedy Krieger Institute, Baltimore, MD, United States, ³Center for Mind Brain Sciences, University of Trento, Trento, Italy, Italy, ⁴Division of Neuroradiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Amide proton transfer (APT) CEST has been used to successfully detect tumors and the effect of radiation necrosis. However, the mechanism of contrast is still somewhat inconclusive. When using low power RF pulses that slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC), saturation-transfer signals are revealed upfield from water in addition to the usual downfield CEST/APT signals. These effects have been attributed to saturation relayed by nuclear overhauser enhancements (NOE) in mobile macromolecules. Here we mapped the amide proton and NOE transfer effects in an alternative effort to study protein-based signals in an infiltrating tumor.

Esmaeil Davoodi-Bojd^1,2, Michael Chopp^3,4, Hamid Soltanian-Zadeh^2,5, Shiyang Wang^1,6, Guangliang Ding¹, and Quan Jiang^1
1Neurology, Henry Ford Health System, detroit, MI, United States, ²Electrical and Computer Engineering, University Of Tehran, Tehran, Tehran, Iran,³Neurology, Henry Ford Hospital, detroit, MI, United States, ⁴Physics, Oakland University, Rochester, MI, United States, ⁵Radiology, Henry Ford Health System, detroit, MI, United States, ⁶Radiology, University of Chicago, Chicago, IL, United States

In this work, a new model is proposed to estimate Water Exchange Ratio (WXR) –the ratio of exchanged spins during diffusion time, Δ, between intra and extra axonal space using multi-shell DWMR imaging. Injury (such as MS, stroke, and TBI) to the axonal membrane or myelin sheath will likely change WXR. By measuring this parameter, the proposed model can discriminate between normal and injured fiber tracts induced by TBI or other diseases which affect the exchange parameters of the tissue. This model also may be used to estimate other micro-structural parameters like radius, density, and diffusion coefficients.

Ivan I. Maximov¹, Heike Thoennessen^1,2, Kerstin Konrad^2,3, Laura Amort^1,4, Irene Neuner^1,4, and Nadim Jon Shah^1,5
1Institute of Neuroscience and Medicine 4, Forschungszentrum Juelich GmbH, Juelich, Germany, ²Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany, ³Institute of Neuroscience and Medicine 3, Forschungszentrum Juelich GmbH, Juelich, Germany, ⁴Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, ⁵Department of Neurology, RWTH Aachen University, Aachen, Germany

Voxelwise analysis is a powerful and useful technique that allows one to detect white/grey matter changes and to perform inter-subject group comparisons. However, conventional voxelwise approaches suffer from multiple artefacts originating from the absence of a “gold standard” in the data processing pipeline. TBSS is a promising framework that reduces the voxelwise comparison in “skeleton” space. However, this approach is still under debate: does a transition to the FA skeleton space decrease the result variability? We demonstrate that application of the developed robust post-processing framework allows one to reduce the variability of TBSS results. We also found that the TBSS analysis with the developed robust framework exhibits higher reproducibility compared to other DTI algorithms.

Ido Tavor¹, Shlomi Lifshits², Shir Hofstetter¹, and Yaniv Assaf^1
1Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel, ²Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel

Diffusion MRI is widely used in recent years to investigate the relation between brain structure and cognitive abilities, by scanning subjects before and after a learning task. Methodologies applied in such studies require spatial normalization procedure and a statistical comparison in the group level. We propose an approach to execute a permutation test for performing statistical comparison between 2 DTI scans in the single subject level. The main principle is to examine in which voxels the change in DTI parameters is bigger than the inherent noise. We demonstrate that structural brain changes are detectable using such a method.

Kiho Im¹, Michael J. Paldino¹, Olaf Sporns², and Patricia Ellen Grant^3
1Boston Children's Hospital, Harvard Medical School, Boston, MA, United States, ²Indiana University, Bloomington, IN, United States, ³Boston Children's Hospital, Boston, MA, United States

The major contribution of the current study is to provide the first detailed findings and interpretations on abnormal cortical network topology in malformations of cortical development, in particular polymicrogyria, related to extent of abnormal gyral folding. We propose a novel structural connectivity network analysis based on an individual¡¯s primary gyral pattern and topology, which is biologically more meaningful and able to better capture and describe individual brain network.

Y.C. Shih^1,2, H.H. Liu³, C.E. J. Tseng², and Wen-Yih Isaac Tseng^2
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan, ²Center for Optoelectronic Biomedicine, National Taiwan Univerity College of Medicine, Taipei, Taiwan, Taiwan, ³Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan, Taiwan

The hippocampal sclerosis (HS) is the general abnormality observed in patients with mesial temporal lobe epilepsy (MTLE). We have confirmed the altered structural connectivity related to HS or hippocampal atrophy in left MTLE, however, the functional connectivity between these two regions is still unclear. We hypothesized that there were relationships between structural and functional connectivity caused by HS. The present study reveals the relationships among the integrity of the inferior CB, the volume of hippocampal gray matter and the strength of functional connectivity in the lesion side of patients with HS.

Thibo Billiet¹, Louise Emsell¹, Felice D'Arco², Sabine Deprez¹, Judith Verhoeven¹, Ellen Plasschaert³, Ronald Peeters¹, Eric Legius³, and Stefan Sunaert^1
1Radiology, KULeuven, Leuven, Belgium, ²Radiology, University Federico II of Naples, Naples, Italy, ³Human Genetics, UZLeuven, Leuven, Belgium

"unidentified bright objects" are brain lesions occurring in neurofibromatosis type 1. They are related to learning disabilities. Nevertheless knowledge about their exact nature is limited. Using relaxometry and diffusion measures a detailed description of microstructure can now be obtained.

Vincent Lee¹, Amy C. Nau^2,3, and Kevin C. Chan^4,5
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²Sensory Substitution Laboratory, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Departments of Ophthalmology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, United States

This study explored the effect of blindness on visual brain reorganization by analyzing the microstructural changes in fiber architecture in both congenitally blind and acquired blind individuals using diffusion tensor MR imaging. The fractional anisotropy maps from the experimental groups and normally sighted individuals were processed and registered using tract based spatial statistics and evaluated using both voxel-wise and region-of-interest (ROI) based non-parametric analyses. The voxel-wise non-parametric tests uncovered statistically significant FA differences in the bilateral optic radiation and in other major fiber tracts associated with visual processing. ROI based analysis showed that both congenitally blind and acquired blind subjects had lower FA than normal controls in the major fiber tracts connected to the visual cortex. Our results suggested that plastic changes may occur in both early blindness and late onset of blindness after completion of traditional critical period of visual brain development.

Jong-su Baeck¹, Jeehye Seo¹, Seong-Uk Jin¹, Jang Woo Park¹, Moon Han¹, Yongmin Chang^2,3, and Yong Won Cho^4
1Department Medical & Biological Engineering, kyungpook national University, Daegu, Korea, ²Department of Radiology, Kyungpook National University, Daegu, Korea, ³Department of Molecular Medicine, kyungpook national University, Daegu, Korea, ⁴Department of Neurology, Kemyung University School of Medicine, Daegu, Korea

In the present study, using voxel-based DTI, we aimed to explore the possible mechanism of altered integrity of brain white matter in RLS patients. RLS patients demonstrated decreased FA in the genu of corpus callosum and frontal white matter adjacent to inferior frontal gyrus (Brodmann 10) compared with healthycontrol subjects (P<0.001). For areas of decreased FA, both AD and RD were higher than that in control subjects. Decreased FA in RLS patients revealed the microstructural abnormalities in the genu of corpus callosum and the frontal white matter. Among these areas, increased RD in the frontal white matter suggested the demyelination of white matter consistent with findings from previous postmortem study. Increased AD seems to be associated with reduced axonal density. Taken together, our findings may suggest that both loss of axonal density and loss of myelin were responsible for the white matter abnormalitiesin RLS patients.

Rajesh Kumar¹, Paul M. Macey², Mary A. Woo², Frisca L. Yan-Go³, and Ronald M. Harper^1
1Neurobiology, University of California at Los Angeles, Los Angeles, CA, United States, ²UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, United States, ³Neurology, University of California at Los Angeles, Los Angeles, CA, United States

Obstructive sleep apnea (OSA) patients show gray matter and axonal injury in areas that control autonomic, cognitive, and mood functions, deficient in OSA; however, the nature of brain injury (axonal or myelin) in newly-diagnosed OSA subjects is unclear. We examined global and regional axial and radial diffusivity in newly-diagnosed OSA, which assess axonal and myelin changes, respectively, and found significantly reduced global diffusion values, reflected as localized changes in various brain areas, including the medullary, cerebellar, basal-ganglia, and limbic sites. Radial diffusion changes in OSA were more widespread than axial, indicating predominant myelin pathology over axons, possibly resulting from hypoxemia.

Rajesh Kumar¹, Mary A. Woo², Paul M. Macey², Gregg C. Fonarow³, and Ronald M. Harper^1
1Neurobiology, University of California at Los Angeles, Los Angeles, CA, United States, ²UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, United States, ³Cardiology, University of California at Los Angeles, Los Angeles, CA, United States

Heart failure (HF) patients show gray matter and axonal deficits in multiple brain sites; however, it is unknown whether the structural changes are accompanied by acute or chronic tissue pathology. Those changes can be differentiated by mean diffusivity (MD) procedures. We assessed HF subjects with MD procedures, and found increased MD values in multiple brain sites, including limbic, basal ganglia, thalamic, hypothalamic, and cerebellar regions, compared to control subjects, indicating chronic tissue changes in these areas. The pathological mechanisms contributing to chronic injury in HF may include perfusion or hypoxic processes accompanying the condition.

Khader M. Hasan¹, MA Liangsuo², Larry A. Kramer¹, Scott D. Lane², Joel S. Steinberg², Ponnada A. Narayana¹, and Gerry F. Moeller^2
1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, Texas, United States, ²Psychiatry and Behavioral Sciences, University of Texas Health Science Center at, Houston, Texas, United States

In this work we applied atlas-based methods to identify the macro and microstructural correlates of cocaine effects by incorporating white matter (WM) connections in addition to the limbic-thalamic-striatal-cortical regions as previously reported. Our study indicates that GM mean diffusivity of the cingulate cortex and thalamus may serve as early markers that could precede subsequent long term effects of cocaine on WM pathways.

Kenji Ito¹, Kuniaki Ogasawara², Masakazu Kobayashi², Makoto Sasaki¹, Kohsuke Kudo¹, Fumio Yamashita¹, Satomi Higuchi¹, Jonathan Goodwin¹, Ikuko Uwano¹, and Suguru Yokosawa^1
1Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Morioka, Iwate, Japan, ²Department of Neurosurgery, Iwate Medical University, Morioka, Iwate, Japan

This study investigated cerebral white matter (WM) changes in diffusion fractional anisotropy (FA), which are associated with altered cognitive function after carotid endarterectomy (CEA), by applying tract-based spatial statistics (TBSS). In 11 patients showing postoperative improvement in cognitive function, the mean FA values in the cerebral WM significantly increased after CEA, but no significant changes were found in 78 other patients. Furthermore, FA values in the bilateral frontal WM increased after CEA in patients with improved cognition. TBSS can detect bilateral increases in FA values in the frontal WM, and these increases are associated with cognitive improvement after CEA.

Il Yong Chun¹, Allan Diaz¹, Yun-Jang Jin¹, Xiaodong Li¹, Larry Leverenz², Eric Nauman³, and Thomas Talavage^1,4
1School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana, United States, ²3Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, United States, ³School of Mechanical Engineering, Purdue University, West Lafayette, Indiana, United States,⁴Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States

Building on our study of repetitive blows in contact sports, we introduce a bootstrapped z-score analysis as a robust voxel-wise statistical analysis method to detect deviations from normal white matter fractional anisotropy. With this approach, we evaluate the progression of changes in fractional anisotropy (FA) over time, using DW-MRI scans from pre-season to post-season. These changes provide strong evidence that contact sports athletes, especially American football players, who receive many blows to the head during the season, exhibit likely chronic white matter injuries.

Keumsil Lee¹, Daniel H.-E. Chang¹, Huali Wang², and Min-Ying Su^1
1Center for Functional Onco-Imaging, Department of Radiological Sciences, University of California, Irvine, CA, United States, ²Department of Geriatric Psychiatry, Peking University Institute of Mental Health, Beijing, China

The impact of white matter lesion (WML) on FA maps is studied. We selected a group of AD patients without WML based on the Age-Related White Matter Changes (ARWMC) rating scale of the European Task Force, and another group of AD patients with severe WML for comparison. The AD subjects with severe WML show smaller differences compared to normal control (NC), while the AD subjects without WML show a more extensive difference compared to the NC. The results suggest that the AD group containing white matter lesions have more heterogeneity white matter abnormality, thus less likely to show significant differences.

Claudia Metzler-Baddeley¹, Roland John Baddeley², Jaime Canteras³, Anne Rosser⁴, Elizabeth Coulthard⁵, and Derek K. Jones^1
1CUBRIC, Cardiff University, Cardiff, Wales, United Kingdom, ²Experimental Psychology, Bristol University, Bristol, Avon, United Kingdom, ³Music Factory, Bristol, Avon, United Kingdom, ⁴Biosciences, Cardiff University, Cardiff, Wales, United Kingdom, ⁵Dementia and Cognitive Neurosciences, Bristol University, Bristol, Avon, United Kingdom

Huntington’s disease is characterised by basal ganglia and white matter degeneration leading to motor and executive dysfunction. This pilot study investigated for the first time a novel drumming training paradigm that combines sequence learning, timing and multi-tasking with practise of hand movement coordination. Diffusion MRI indices of white matter microstructure in frontal motor pathways and working memory performance were compared pre- and post-training. The results show improvements in white matter microstructure and in working memory function and hence potential for an effective clinical intervention.

Julio Acosta-Cabronero¹, Dina Kronhaus², Robert J. Arnold¹, Guy B. Williams³, and Peter J. Nestor^4
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ²Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ³Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ⁴Plasticity and Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Saxony-Anhalt, Germany

This study explored the hypothesis that diffusion tensor imaging (DTI) abnormalities in Alzheimer’s disease (AD) should capture axonal damage or cell death. This was done by testing the linear dependence of DTI-derived metrics on hippocampal atrophy using whole-brain and region of interest approaches. The results revealed that in the same white matter areas where axial diffusivity (1) is abnormal early, progressive change in radial diffusivity (RD) and fractional anisotropy (FA) – but not in 1 – predict atrophy in the hippocampus. What is then 1 sensitive to in very early disease stages?

Ashish Raj¹, Amy Kuceyeski, PhD¹, Michael Weiner, MD², and Bruce Miller, MD^3
1Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ²Department of Radiology, University of California, San Francisco, San Francisco, CA, United States, ³Department of Neurology, University of California, San Francisco, San Francisco, CA, United States

Recent studies on prion-like proteopathy of dementias suggest transmission along fiber pathways of the brain network. In a recent paper we modeled the macroscopic consequences of network-centric propagation as a diffusion process on the structural (tractography-derived) brain network. The model accurately recapitulated known patterns of atrophy seen in several dementias. To our knowledge network diffusion constitutes the first fully quantitative, testable model of macroscopic transmission of degenerative processes in the brain. Its neurologic impact arises from its implication that diverse proteopathic etiologies could produce shared spatial patterns whose explanation requires neither selective vulnerability nor focal points of origin, nor differential stressor loads. Here we highlight this new advance and put it in the wider context of graph theoretic modeling of dementias. We believe that researchers involved in neuroimaging of neurodegenerative diseases can benefit from a deeper understanding of this exciting new technology.

Juliette Driessen^1,2, Joanna Caldas-Magalhaes³, Chris Terhaard³, Luuk M. Janssen¹, Wilko Grolman^1,2, and Marielle E.P. Philippens^3
1Otorhinolaryngology – Head and Neck Surgery, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Rudolf Magnus Institute of Neuroscience, Utrecht, Utrecht, Netherlands, ³Radiotherapy, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

For head and neck squamous cell carcinoma, a correlation between local failure after (chemo)radiotherapy and diffusivity has been found . However, the pathohistological basis for this is not clear. Therefore, we performed imaging validation with whole-mount sections. We found a strong relationship between ADC and both cellularity and nuclear-to-cytoplasm ratio. Stromal ratio was indistinguishable from cellularity due to strong interdependence. Besides the association with higher ADC, local failure after chemoradiotherapy has also been related to higher stromal fractions. This suggests that the relationship between local failure and ADC might be partly attributed to the tumor-stroma component.

Tim Leiner¹, Eveline Alberts², Niels Blanken¹, Mark Stoesz², Martijn Hartjes², and Jeroen Hendrikse^1
1Department of Radiology, Utrecht University Medical Center, Utrecht, Netherlands, ²Clinical Science Department, Philips Healthcare, Eindhoven, Netherlands

Decreased MR examination times are clinically of high interest in order to improve the cost-effectiveness of MR imaging. We demonstrate that application of recent advances in MR hardware and software enable faster imaging compared to standard vendor supplied protocols. For 4 very commonly per-formed MR studies (brain, cervical spine, knee and ankle) we were able to bring image acquisition down to less than 8 minutes, while still satisfying the criteria as set forth in the most recent version of the ACR Clinical Image Quality Guide.

Christina Louise Sammet¹, Adesola Ogunniyi², Ann B. Ragin¹, Robert L. Murphy¹, Steffen Sammet³, and Godwin Inalegwu Ogbole^2
1Northwestern University, Chicago, IL, United States, ²University of Ibadan, Ibadan, Oyo, Nigeria, ³University of Chicago, Chicago, IL, United States

This educational exhibit will explore the neuroimaging capabilities and challenges of low-field, permanent magnet MR imaging technologies increasingly utilized in developing countries. As the MR community dedicates itself to optimizing neuroimaging at ultra-high field, the challenges of low-field (<0.4T) imaging are infrequently discussed. This exhibit summarizes the state-of-the art in permanent magnet MRI with the intention to encourage interest in the improvement of existing systems and their utilization for collaborative neuroimaging research in the developing world.

Masaaki Hori¹, Koji Kamagata¹, Mariko Yoshida¹, Nozomi Hamasaki², Keigo Shimoji¹, Yuriko Suzuki³, Yoshitaka Masutani⁴, Issei Fukunaga^5,6, and Shigeki Aoki^1
1Department of Radiology, School of Medicine, Juntendo University, Tokyo, Japan, ²Juntendo University Hospital, Tokyo, Japan, ³Philips Electronics Japan, Ltd., Tokyo, Japan, ⁴Division of Radiology, and Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, ⁵Department of Radiology, Juntendo University, Tokyo, Japan, ⁶Graduate School of Human Health Sciences, Tokyo, Japan

The purpose of this exhibit is to present the effects of the combinations of b-values and Rician noise filter for DTI and DKI metrics in the spinal cord, for clinical use in particular. The different combinations of b values result in the different diffusion metrics, such as mean kurtosis. Therefore, suitable selection of b values is important for the specific purpose of the study. Moreover, Rician denoising technique lead to appropriate DKI and DTI metrics estimation, mean kurtosis in particular because the diffusion MR images of spinal cord often suffer from low signal-to-noise ratio in vivo.

Michael H. Buonocore^1,2, David G. Amaral³, Gerald J. Sonico², Jeff Bennett³, and Martin Styner^4
1Radiology, UC Davis, Sacramento, CA, United States, ²Imaging Research Center, UC Davis, Sacramento, CA, United States, ³Psychiatry and Behavioral Sciences, UC Davis, Sacramento, CA, United States, ⁴Psychiatry and Computer Science, University of North Carolina at Chapal Hill, Chapel Hill, NC, United States

This abstract reviews the process of selecting RF coils, pulse sequences and scan parameters for structural and functional brain imaging of non-human primates (NHPs). Compared to these factors in human imaging, the smaller size of the NHP brain, desire for high spatial resolution, and ability to scan for longer durations without head motion, lead to selections that are uncommon in human imaging yet generate NHP images with high spatial resolution, tissue contrast, and SNR. The unique characteristics of NHP imaging provide opportunities for protocol optimization that are not practical, or not available, for human imaging protocols.

Norbert Campeau¹ and Alice Patton^1
1Radiology, Mayo Clinic, Rochester, MN, United States

3D Phase contrast angiographic imaging of the brain and neck: Initial clinical experience in 100 patients. Specific protocols for performing 3D-Phase contrast MRA and MRV of the brain, and MRA of the neck are presented, including optimal choice of VENC, acquisition volume orientation, matrix size, and use of SAT bands. Comparison with available 3D-TOF brain MRA, 2D-TOF and bolus gadolinium brain MRV, 2D-TOF neck MRA, and bolus gadolinium neck MRA is provided. 3D Phase contrast MRA/MRV does not require IV gadolinium, and is excellent choice for imaging in patients with gadolinium allergy or renal insufficiency. Bolus gadolinium MRA remains the "gold standard", however 3D phase contrast techniques can provide comparable and occasional superior results.

Koji Kamagata¹, Masaaki Hori¹, Keigo Shimoji¹, Michimasa Suzuki¹, Atsushi Nakanishi¹, Hiroyuki Tomiyama², Yumiko Motoi², Issei Fukunaga³, Humitaka Kumagai¹, Nobutaka Hattori², and Shigeki Aoki^1
1Department of Radiology, Juntendo university, Tokyo, Japan, ²Department of Neurology, Juntendo university, Tokyo, Japan, ³Department of Radiology, Juntendo University, Tokyo, Japan

Conventional MR imaging of Parkinson disease (PD) is frequently normal or nonspecific. However, advanced MR techniques, such as diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and arterial spin labeling (ASL) allow us to evaluate changes related to the pathophysiology of PD. The purpose of this exhibit is to review the conventional and advanced MR imaging of PD and to present some new data from ASL and DKI studies of PD.

Da Shi^1,2, Jiachen Zhou^2,3, Su Xu^2,3, and Rao P. Gullapalli^2,3
1Biochemistry and Molecular Biology, University of Maryland Baltimore, Baltimore, MD, United States, ²Core for Translational Research in Imaging @ University of Maryland, University of Maryland Baltimore, Baltimore, MD, United States, ³Diagnostic Radiology and Nuclear Medicine, University of Maryland Baltimore, Baltimore, MD, United States

Recent use of MRI to study Fragile X syndrome (FXS) has revealed changes in brain during development. However, there is still a gap in knowledge about developmental alterations in the FXS and Fmr1 knockout mouse model. We have found deceased diffusion parameters in many regions of the Fmr1 KO mouse brain compared to wild-type mice at postnatal day (PND) 30. A general decreasing trend of mean, axial and radial diffusivity were found in whole brain and specific brain regions of Fmr1 KO mice. Preliminary histological correlation found decrease staining of myelin in Fmr1 KO mice at PND 30.

Houshang Amiri^1,2, Anna C. Navis³, Jolanda de Vries², William P. Leenders³, and Arend Heerschap^1
1Radiology Department, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands, ²Tumor Immunology Department, Nijmegen Centre for Molecular Life Sciences, Nijmegen, Gelderland, Netherlands, ³Pathology Department, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands

Combined DTI and ASL with T2* imaging Discriminates Between Angiogenic and Highly Diffuse Infiltrative Brain Tumor Models: A Study at 11.7 Tesla We combined diffusion tensor imaging with arterial spin-labeling and T2* imaging to differentiate between angiogenis and highly diffuse infiltrative xenograft glioma models. Fractional anisotropy, apparent diffusion coefficient and cerebral blood flow (CBF) not only allowed us to detect the fibers abnormalities but also to discriminate between our models. Additionally, T2* of tumors correlated with CBF, interestingly. Our data suggests that employed techniques provides better tumor delineation and phenotypic characterization of angiogenic and diffuse infiltrative tumor tissue.

Yohan van de Looij^1,2, Volodomyr Petrenko³, Petra Susan Hüppi¹, Rolf Gruetter^4,5, Jozsef Kiss³, and Stéphane V. Sizonenko^1
1Division of Child Growth & Development, University of Geneva, Geneva, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Department of Fundamental Neurosciences, University of Geneva, Geneva, Switzerland,⁴Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁵Department of radiology, University of Geneva and Lausanne, Geneva and Lausanne, Switzerland

Despite the importance of apoptosis in the brain pathology, in vivo diagnostic of this process is still not developed. The aim of this work was to evaluate the possibility of using non-invasive MR techniques to detect apoptotic neuronal death in the rodent cerebral cortex. Neuronal ablation was induced by using a diphtheria toxin and diphtheria toxin receptor system. MRS and DTI detected metabolic and micro-structural alterations induced by apoptotically dying neurons within the cortex. Further experiments are in progress to assess precisely acute and long-term apoptosis-induced MRI changes.

Xiaohua Hong^1,2, Silun Wang¹, and Jinyuan Zhou^1
1Radiology, Johns Hopkins University, Baltimore, Maryland, United States, ²Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Several MRI modalities were applied to rat U87MG tumors that were treated with radiotherapy (40 Gy). It was found that the APT signal in the radiated tumor significantly decreased from day 3 post-treatment and the ADC signal significantly increased from day 6 post-treatment. Our results show that both APT and ADC were biomarkers that can early assess glioma response to radiotherapy.

Monika Huhndorf¹, Olga Will², Rolf Mentlein³, Olav Jansen¹, and Susann Boretius^2
1Institute of Neuroradiology, University Medical Center Schleswig-Holstein, Kiel, Germany, ²Biomedical Imaging, Diagnostic Radiology, Christian-Albrechts-University, Kiel, Germany, ³Institute of Anatomy, Christian-Albrechts-University, Kiel, Germany

High resolution susceptibility weighted imaging (SWI) was used in comparison with other MR-contrasts at 7T in order to visualize iron-labeled C6-glioma cells in a rat model. Although even very low iron concentrations were detectable by SWI, no significant iron accumulation was found at the margin of advanced tumors, suggesting persistence of the iron particles at the site of the primary cells in the tumor center.

Lindsey A. Leigland¹, Matthew D. Budde², and Christopher D. Kroenke^1,3
1Advanced Imaging Research Center and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States,²Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ³Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United States

The aim of this research was to investigate the effects of prenatal exposure to ethanol on diffusion tensor imaging (DTI) measurements in the developing cerebral cortex, and directly compare histological evidence of disrupted neuronal morphology in a rat model of fetal alcohol spectrum disorders (FASD). Data indicated disruptions in cortical developmental DTI patterns seen in response to prenatal exposure to ethanol, related via histology to abnormal neuronal morphology and differentiation. Given the sensitivity of DTI to detect abnormalities caused by ethanol exposure during gestation, DTI is introduced as a potential diagnostic methodology for FASD.

Holly Elizabeth Holmes¹, Nick M. Powell*^1,2, Jack A. Wells¹, Niall Colgan¹, James M. O'Callaghan¹, Da Ma^1,2, Marc Modat², Manuel Jorge Cardoso², Simon Richardson¹, Bernard M. Siow¹, Michael J. O'Neill³, E Catherine Collins⁴, Elizabeth Fisher⁵, Sebastien Ourselin², and Mark F. 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, ³Eli Lilly & Co. Ltd, Windlesham, Surrey, United Kingdom, ⁴Eli Lilly & Co. Ltd, Indianapolis, Indiana, United States, ⁵Institute of Neurology, University College London, London, Greater London, United Kingdom

Preclinical MRI has become a promising technique to examine mouse brain morphology. In this study, we employed an optimised sequence for high resolution 3D in vivo imaging. We used a novel automatic image analysis toolbox to examine a mouse model of Alzheimer’s disease (rTg4510). Tensor-based morphometry analysis revealed significant changes in local brain volume between this model and age-matched wild-types. Our findings correspond to expected changes, including hippocampal and forebrain atrophy, as well as ventricular dilation.

Su Xu^1,2, Kaspar M. Keledjian³, Jiachen Zhuo^1,2, Xin Lu^1,2, Vladimir V. Gerzanich³, J. Marc Simard³, and Rao P. Gullapalli^1,2
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States, ²Core for Translational Research in Imaging @ Maryland, Baltimore, Maryland, United States, ³Departments of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, United States

In this study we investigated in vivo changes using advanced MRI to understand the effects of a blast overpressure traumatic brain injury on a direct cranial blast injury rat model. Diffusion kurtosis imaging (DKI) and proton MRS was used before and up to 28 days following the blast injury. Results indicate that while no structure imaging and MRS changes were found until 14 days following injury, significant structural changes were found in the internal capsule, cerebellum and cortex after 14 days using DKI. These changes were also accompanied by changes in neurometabolites at 28 days in the cerebellum suggesting delayed effects following blast injury which is consistent with mild TBI.

Lian Li¹, Michael Chopp^1,2, Guangliang Ding¹, Changsheng Qu³, Qingjiang Li¹, Siamak P. Nejad-Davarani¹, and Quan Jiang^1
1Neurology, Henry Ford Hospital, Detroit, MI, United States, ²Physics, Oakland University, Rochester, MI, United States, ³Neurosurgery, Henry Ford Hospital, Detroit, MI, United States

While cell transplantation has potential as an effective therapeutic strategy to attenuate secondary injury after traumatic brain injury (TBI), several key issues regarding optimization of basic transplantation techniques, such as timing of transplantation, remain to be addressed. Using MRI, we tested the hypothesis that acute engraftment of human marrow stromal cells (hMSCs) into the brain subjected to TBI provides an advanced therapeutic effect as compared to delayed transplantation. Our data demonstrate that acute cell intervention extends the time range of therapeutic benefit by initiating the therapeutic effects earlier, resulting in an enhanced protective and therapeutic effect.

Guangliang Ding¹, Michael Chopp^1,2, David J. Poulsen³, Lian Li¹, Changsheng Qu⁴, Qingjiang Li¹, Siamak P. Nejad-Davarani¹, John Budaj^1,5, Hongtao Wu⁴, Asim Mahmood⁴, and Quan Jiang^1
1Neurology, Henry Ford Hospital, Detroit, Michigan, United States, ²Physics, Oakland University, Rochester, Michigan, United States, ³Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, United States, ⁴Neurosurgery, Henry Ford Hospital, Detroit, Michigan, United States,⁵Biomedical Engineering, Oakland University, Rochester, Michigan, United States

Traumatic brain injury (TBI) is an important public health problem in Western countries. There is an urgent need to develop a novel approach for the treatment of TBI. With a CCI model of TBI in young Wistar rats, methamphetamine treatment of TBI significantly improved white matter reorganization at 5 to 6 weeks after TBI, compared with saline treatment, based on the MRI FA measurements. And significant correlation was detected between the FA and histological BLFB measurements. It suggested that the the improved white matter may contribute to the functional recovery after TBI in rat.

Chao-Yu Shen^1,2, Zhen-Hui Li¹, Tao-Tao Chen¹, Yeu-Sheng Tyan^1,2, and Jun-Cheng Weng^1,2
1School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

In the study, we used a linear accelerator as the source of radiation to establish an adult rabbit model for single-dose cerebral hemisphere exposure radiation-induced brain injury, and afterward, it longitudinally evaluated the changes in various brain compartments on a 1.5T clinical MR scanner by using T2 weighted imaging (T2WI) and diffusion tensor imaging (DTI) indices: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) mapping. It is hoped that this experimental model can be used to evaluate the neuro-toxic adverse effects of irradiation treatment.

Blanca Lizarbe¹, Pilar Lopez-Larrubia¹, and Sebastián Cerdán^2
1Instituto Investigaciones Biomedicas "Alberto Sols" CSIC-UAM, Madrid, Madrid, Spain, ²Instituto de Investigaciones Biomédicas - CSIC, Madrid, Madrid, Spain

Obesity is a pandemic syndrome associated with the most prevalent and morbid pathologies. Body adiposity is thought to be regulated systemically through an endocrine ‘adiposity’-negative feedback loop, including mainly leptin2. Disruptions in the leptin signalling systems are associated with obesity in humans and mice, and the leptin-null ob/ob mouse model exhibits decrease energy expenditure, hyperphagia and obesity. Here, we prpose the fDWI approach to the evaluation of ob/ob mice in fed and fasted conditions, to validate the use of fDWI in animal models with hypothalamic disfunctionality and characterize the individual responses to fasting of relevant hypothalamic nuclei from leptin-null mice.

Yuguang Meng¹, Longchuan Li², Xiaoping P. Hu², Jocelyne Bachevalier³, Christa Payne³, and Xiaodong Zhang^1,4
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States, ³Yerkes National Primate Research Center and Department of Psychology, Emory University, Atlanta, GA, United States, ⁴Division of Neuropharmacology and Neurologic Disease, Emory University, Atlanta, GA, United States

An earlier study on the impact of hippocampal lesions on the integrity of the corpus callosum (CC) and its inter-hemispheric connectivity indicated a reduction in the surface area of the posterior CC. To assess whether the same CC changes will follow the hippocampal lesions occurred in early life, the present study measured CC integrity in adult monkeys with neonatal hippocampal lesions. Mean diffusivity data showed alterations of posterior CC segment and transcallosal fibers from the posterior parietal and retrosplenial cortex, the damage of which would impair visuospatial processing functions due to Neo-H lesions.

Yi-Ling Wu¹, Sheng-Min Huang¹, Shin-Lei Peng¹, Yi-Chun Wu², Tao-Chieh Yang³, Jee-Ching Hsu⁴, Ming-Long Wu⁵, and Fu-Nien Wang^1
1Department of Biomedical Engineering & Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, ²Animal Molecular Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ³Department of Neurosurgy, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ⁴Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ⁵Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan

In this study we investigated the resting state (RS) networks of attention deficit and hyperactive disorder (ADHD) using spontaneously hypertensive rats (SHR). RS network of SHR was found to be more active than normal rat in primary somatosensory (S1) and insular cortex region. The hyperactivity in S1 is speculated to be the possible reason of attention deficit since rats are sensitive to external changes. Though the detail connections of RS network and physiological functions should be further examined, our works suggest the feasibility to evaluate RS network differences by rat model. More case studies of ADHD could be conducted via rat model.

Valerio Zerbi^1,2, Diane Jansen¹, Maarten Van Beek¹, Roy Haast¹, Andor Veltien³, Laus M. Broersen⁴, Jack JA Van Asten³, Arend Heerschap³, and Amanda J. Kiliaan^1
1Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Netherlands, ²Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, Netherlands, ³Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Netherlands, ⁴Nutricia Advanced Medical Nutrition, Centre for Specialised Nutrition, Wageningen, Netherlands, Netherlands

Research into Alzheimer’s disease (AD) suggests that dietary behavior may affect the course of AD. A specific combination of omega-3 fatty acids with precursors and cofactors in membrane synthesis was developed for the dietary management of AD. In this study, we tested the hypothesis that a specific nutrient-combination diet is able to positively influence cerebral hemodynamics, metabolite levels and white- and gray matter diffusion in mouse models resembling vascular risk factors for AD (apoE4 and apoE-ko). Results showed improved brain capillary vasoactivity, metabolism and neurodegeneration our specific multi-nutrient diet, and thus may contribute to slow AD pathology development.

Sunil Koundal¹, Sonia Gandhi¹, Tanzeer Kaur², Subash Khushu¹, and Rajendra P. Tripathi^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, India, ²Department of Biophysics, Panjab University, Chandigarh, Panjab, India

High altitude related exposure results in decreased oxygen supply to brain. Brain being most sensitive to hypobaric hypoxia, gets adversely affected. Our study investigates the changes in metabolic profiles of rat brain’s hippocampus region due to acute hypobaric hypoxia stress and recovery using invivo magnetic resonance spectroscopy. Results showed significant decrease in levels of glutamate,myoinositol,NAA,creatine but increase in choline indicating hypobaric hypoxia induced damage in hippocampus of rat brain. These studies can be helpful in detecting early biomarkers for high altitude stress injuries in humans which can further be used for risk assessment & early diagnosis.

Xuan Vinh To^1,2, Chun-Yu Yip¹, Ho Ngoc Na¹, Boon Seng Wong², and Kai-Hsiang Chuang^1,2
1Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, Singapore, ²Department of Physiology, National University of Singapore, Singapore, Singapore, Singapore

To understand the genetic influence of apolipoprotein (Apo) isoforms on the brain in the ageing process, we conducted longitudinal MRI on transgenic mice with human Apo E3 (hApoE3) or hApoE4 genes at 6 and 9 months old. Structural MRI data were analyzed using voxel-based morphometry and identified several regions with increased gray matter volume in E4 mice at both time points. CBF were imaged using pseudo-continuous ASL (pCASL) with spin-echo EPI acquisition. Higher CBF was found in E3 mice at 6 mo but the difference reduced at 9 mo. The different trends in brain volume and CBF indicate genetic influence of Apo and suggest a compensatory mechanism.

Tom Dresselaers¹, Wouter Oosterlinck², Tom Struys^1,3, Kristof Govaerts¹, Ivo Lambrichts³, Paul Herijgers², and Uwe Himmelreich^1
1Department of Imaging & Pathology, KU Leuven, Leuven, Vl.Brabant, Belgium, ²Department of Experimental Cardiac Surgery, KU Leuven, Leuven, Vl.Brabant, Belgium, ³Department of Functional Morphology, Hasselt University, Diepenbeek, Limburg, Belgium

Unilateral Ligation of the common carotid artery (CCA) is usually performed for mouse stroke models. This study shows the impact of such a ligation on the cerebral blood flow using arterial spin labeling in sham operated animals under isoflurane anesthesia. Such ligation of the CCA may impact stroke development at early and later stages in the tMCAO mouse model. We demonstrate that a suture of the CCA avoids interhemispheric differences in CBF. We therefore speculate that this sutured tMCAO model may result in more consistent lesions, less mortality and a more realistic stroke model.

Yuguang Meng¹, Longchuan Li², Xiaoping P. Hu², Jocelyne Bachevalier³, Christa Payne³, and Xiaodong Zhang^1,4
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States, ³Yerkes National Primate Research Center and Department of Psychology, Emory University, Atlanta, GA, United States, ⁴Division of Neuropharmacology and Neurologic Disease, Emory University, Atlanta, GA, United States

A recent diffusion tensor imaging (DTI) study demonstrated that excitotoxic hippocampal lesions in adult macaques alter white matter tracts of the temporal and frontal lobes. In the present study, DTI was used to examine whether similar changes will also be found in adult macaque monkeys with similar selective hippocampal lesions done in infancy. Significant diffusivity alterations were found in the white matter of the temporal stem and ventromedial prefrontal cortex which is involved in memory consolidation and working memory retrieval.

Ling-Yuh Shyu¹, Hao-Hung Tsai^2,3, Yi-Hsin Wang², Shin-Tai Chong^2,4, and Jun-Cheng Weng^2,3
1Department of Parasitology, Chung Shan Medical University, Taichung, Taiwan, ²School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ³Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ⁴Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan

Angiostrongylus cantonensis (A. cantonensis) is a zoonotic nematode parasite residing in the pulmonary arteries and brain of rats. It was first identified and described by Chen in Canton, China, and was reported to cause human diseases in 1945 in Taiwan. Now A. cantonensis is the major cause human eosinophilic meningitis in Taiwan. However, the features of the pathological changes in the brain were limited to diagnostic techniques. Previously the diagnosis was established by immunodiagnosis, lumbar puncture and eosinophilia examination. Fourth- or fifth-stage larvae could be found in the cerebrospinal fluid (CSF) with lumbar puncture. Improper puncture and false immune response resulted in an erroneous diagnosis. Therefore, the purpose of this study was to longitudinally monitor the lesion localization, pathological changes and angiostrongyliasis characterization of rat brain infected with different numbers of A. cantonensis larvae by MRI techniques. The results were also verified with histopathological study. The association between the clinical features of the rats and MRI findings was also addressed.

Christopher D. Kroenke^1,2, Torsten Rohlfing³, Edith V. Sullivan⁴, Adolf Pfefferbaum^3,4, and Kathleen A. Grant^2,5
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, United States, ³Neuroscience Program, SRI International, Menlo Park, CA, United States, ⁴Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, United States, ⁵Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States

A known consequence of prolonged heavy alcohol drinking is reduction of brain tissue volume, including cerebral cortical gray matter. To facilitate systematic characterization of the biological processes underlying this volumetric change, T1-weighted magnetic resonance imaging-based brain volumetric measurements are reported for 18 rhesus macaque (Macaca mulatta) monkeys in the ethanol-naive state, and following 6 and 12 months of voluntary drinking (three time points total). Reductions in cerebral cortical gray matter volume are found following both drinking intervals, and the extent of volumetric reduction is proportional to the average daily intake of ethanol, which ranged from 0.2 to 4.3 g/kg/day.

Tom Dresselaers¹, Tom Struys¹, Wouter Oosterlinck², Sarah Caers¹, Ann Van Santvoort¹, Paul Herijgers², Ivo Lambrichts³, and Uwe Himmelreich^1
1Department of Imaging & Pathology, KU Leuven, Leuven, Vl.Brabant, Belgium, ²Department of Experimental Cardiac Surgery, KU Leuven, Leuven, Vl.Brabant, Belgium, ³Department of Functional Morphology, Hasselt University, Diepenbeek, Limburg, Belgium

Cerebral perfusion deficits are a hallmark of several neurovascular diseases but are recently also coupled to the development and/or progression of neurodegenerative diseases such as Alzheimer’s disease. Besides monitoring basal cerebral blood flow, the cerebral vascular response (CVR) induced by hypercapnic challenges might be a more sensitive and early detectable marker of vascular defects. This study describes the influence of different anaesthetics on the feasibility of non-invasive monitoring CVR in mice. Data show optimal results under ketamine/xylazine anaesthesia in combination with a muscle relaxant to allow proper ventilation to exclude any adverse effects of endogenous breathing patterns.

Sunil Koundal¹, Sonia Gandhi¹, Tanzeer Kaur², Subash Khushu¹, and Rajendra P. Tripathi^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, India, ²Department of Biophysics, Panjab University, Chandigarh, Panjab, India

Ascent to high altitude results in air at low pressure, this condition of hypobaric hypoxia affects brain adversely. We used T2 relaxometry to trace any changes in brain parenchyma due to exposure to hypobaric hypoxia in rat brain. Result showed significant decrease in T2rt in grey matter areas and increase in white matter areas which indicates inhomogeniety and edema in brain tissue respectively indicating changes in tissue architecture at micro level , possibly an neuronal dysfunction and neurotransmitter metabolism.