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

This study was to investigate both signal-to-noise ratio (SNR) and exchange effects on the MWF estimation from Spin-Echo and Steady-State Techniques.

Arun GovindaRao¹, Ramesh Venkatesan¹, Uday Patil², and Abhishek Goyal^1
1Healthcare, General Electric, Bangalore, Karnataka, India, ²GE Global Research, General Electric, Bangalore, Karnataka, India

MRI though considered being an advanced technique for clinical diagnosis has not been accepted clinically as a quantification tool. Reliable and reproducible results have always been a challenge for MRI. For perfusion analysis, commercial vendors report relative functional maps due to various factors that prevent quantification. The criticality in reporting quantitative values is needed in perfusion based analysis. Stroke for example, decision for selection of candidates that require tPA is an task for clinicians using relative values, Quantification can help identify candidates accurately. Automated approach for normalizing the functional maps can reduce user induced variability leading towards more reproducible results.

Mingyi Li¹, Erik Beall¹, and Mark Lowe^1
1Cleveland Clinic, Cleveland, Ohio, United States

When investigating intrinsic connectivity type of measure on fMRI datasets, we used Matlab Parallel Computing Toolbox and Matlab Compiler Toolbox on Linux cluster to greatly reduce the computation time. The same solution and methodology could also be useful for other researchers, especially those who are using Matlab in their data processing pipeline.

MARTINA ABSINTA^1,2, GOVIND NAIR¹, THOMAS TALBOT³, MASSIMO FILIPPI², ABHIK RAY-CHAUDHURY⁴, CARLOS A. PARDO⁵, and DANIEL S. REICH^1
1Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke (NINDS), NIH, BETHESDA, MARYLAND, United States, ²Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, MILAN, MILAN, Italy, ³The Laboratory of Cellular and Synaptic Neurophysiology, NICHD, NIH, BETHESDA, MARYLAND, United States, ⁴Surgical Neurology Branch, NINDS, NIH, BETHESDA, MARYLAND, United States,⁵Department of Neurology, Johns Hopkins School of Medicine, BALTIMORE, MARYLAND, United States

We developed a technology to integrate postmortem, high-resolution MRI into the planning and execution of the pathological analysis through the precise localization of the target and cutting coordinates. Compared to standard pathological sectioning, the use of an individually rendered, 3D-printed cutting box for formalin-fixed whole-brains can improve the speed, quality, and accuracy of pathological localization of small findings identi-fied on MRI and should be applicable in a wide spectrum of neurological disorders.

Zhuozhi Dai^1,2, Tao Zhang¹, Yanglong Jia¹, Gen Yan¹, Gang Xiao³, Guishan Zhang¹, Zhiwei Shen⁴, and Renhua Wu^1
1Medical Imaging, Shantou University Medical College, Shantou, Guangdong, China, ²Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada,³Math and Information Technology, Hanshan Normal University, Guangdong, China, ⁴provincial key laboratory of medical molecular imaging, Guangdong, China

Glutamate and GABA are a pair of important neurotransmitters that play a key role in neuropsychiatric diseases. In these studies, we aim to imaging the Glutamte and GABA specifically using chemical exchange saturation transfer technique at 7 Tesla. In addition, we optimized the pre-saturation power respectively and further demonstrated the application in ischemic stroke model in vivo.

Sotirios Bisdas¹, Christian Braun², Ulrike Ernemann¹, and Uwe Klose^1
1Neuroradiology, Eberhard Karls University, Tübingen, Germany, ²Neurology, Eberhard Karls University, Germany

The dependence of perfusion fraction (f) on CSF in IVIM analysis of brain can be demonstrated by DWI measurements with 2 different TEs. The f in cortical or juxta-cortical regions was higher in measurements with longer TE indicating that the fast decaying signal component had long T2, as expected for CSF. In white matter and tumor tissue, f showed no dependence on TE. Considering the influence of CSF on f values and the robustness of the method in lesions located in white matter and tumors is very important prior to any clinical dissemination of IVIM analysis in brain pathologies.

Jorge Arrubla¹, Lukas Breuer¹, Nuno da Silva¹, Jürgen Dammers¹, Irene Neuner^1,2, and N. Jon Shah^1,3
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Jülich, Jülich, NRW, Germany, ²Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, NRW, Germany, ³JARA - Faculty of Medicine, RWTH Aachen University, Aachen, NRW, Germany

In this study we investigate components of the pulse artefact in EEG data recorded at 9.4 T using a combination of ICA, ICASSO and CTPS. We found that the pulse artefact can be separated into different deflections, depending on the phase of the heartbeat, which contribute differently to the resulting artefact. It was possible to identify a link between the amplitude of the pulse artefact and the age of our volunteers, suggesting that the pulse artefact has a strong dependence on what we hypothesize is the arterial compliance.

Jianhua Yan¹, Jason Chu-Shern Lim¹, and David W Townsend^1
1A*STAR-NUS, Clinical Imaging Research Center, Singapore, Singapore, Singapore

Image resolution of MRI is limited by several factors such as hardware, signal to noise ratio, hardware and time limitations or patient’s comfort. In typical clinical settings, several types of images are obtained with different voxel resolutions. Typically, resolution of through-plane is lower than that of in-plane. In many applications, such as image segmentation or registration, voxel size of low-resolution (LR) image is desired to match with a higher-resolution dataset. Traditionally, interpolation techniques such B-spline interpolation were applied. Super-resolution technique has been emerged as an effective way to improve the resolution, signal-to-noise ratio and acquisition time trade-offs compared with direct high-resolution (HR) acquisition. Here, an alternative super-resolution method with intermodality priors from another HR MRI is proposed. In particular, we aim to improve resolution of LR T2-weighted image with help of HR T1-weighted image

Didem Aksoy¹, Murat Aksoy¹, Julian Maclaren¹, Jakob Ehrl¹, and Roland Bammer^1
1Radiology, Stanford University, Stanford, CA, United States

Prospective motion correction is gaining popularity to prevent motion artifacts in MRI of the brain. In many cases, an optical system, such as a camera, is used to track head position. Many authors have claimed, or implied, that one of the advantages of the technique is that it is applicable to any imaging sequence, since it operates independently from the MRI scanner. The purpose of this work was to test this claim by developing and evaluating a complete neuroimaging protocol compatible with optical prospective motion correction.

Hui Xue¹, Peter Kellman¹, Souheil Inati², Thomas Sorensen³, and Michael Schacht Hansen^1
1Magnetic Resonance Technology Program, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States, ²National Mental Health Institute, National Institutes of Health, Bethesda, Maryland, United States, ³Department of Computer Science, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Applying non-linear reconstruction to high resolution 3D MRI is challenging because of the lengthy computing time needed for those iterative algorithms. To achieve practical processing duration to enable clinical usage of non-linear reconstruction, we have extended previously published Gadgetron framework to support distributed computing in a cloud environment. This extension is named GT-Plus. A cloud version of 3D l1-SPIRiT was implemented on the GT-Plus framework. We demonstrate that a 3mins reconstruction could be achieved for 1mm3 isotropic resolution neuro scans with significantly improved image quality using two dimensional acceleration factors of R=3×2 and 3×3.

Quentin Duché^1,2, Giulio Gambarota^1,2, Isabelle Merlet^1,2, Oscar Acosta^1,2, and Hervé Saint-Jalmes^1,2
1Université de Rennes 1 - LTSI, Rennes, Bretagne, France, ²INSERM, UMR 1099, Rennes, France

Many disorders such as multiple sclerosis or focal cortical dysplasia (FCD) require the use of MRI to precisely delineate size ­limited lesions. Optimizing MRI sequences to enhance the contrast between healthy and pathological tissues is necessary. In addition, improving brain images post­processing algorithms of pathological subjects where usual assumptions are void is an important task. For this purpose, it is of primary interest to develop test objects able to mimic the aspect of certain brain lesions. This will allow the optimization for both MRI sequences and post­processing algorithms. In this work, we present a useful test object for sequences optimization.

Mauro DiNuzzo^1,2, Silvia Mangia³, Bruno Maraviglia^1,4, and Federico Giove^1,2
1MARBILab, Enrico Fermi Center, Rome, Rome, Italy, ²Department of Physics, U Sapienza, Rome, Rome, Italy, ³CMRR, U Minnesota, Minneapolis MN, United States, ⁴Santa Lucia Foundation IRCCS, Rome, Italy

We developed a kinetic model of rat brain metabolism including electrophysiological information related to short-term synaptic plasticity in order to examine the coupling between neuronal activity, BOLD, and cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRGlc). We found that post-synaptic activity correlates with CMRO2 and BOLD, while pre-synaptic spiking activity correlates with CMRGlc. In particular, axonal action potentials, albeit consuming less energy than dendritic excitatory postsynaptic potentials, are found to be the primary determinants for the decrease in oxygen/glucose index at firing rates above 4-6 Hz. Our results are relevant for further understanding neurovascular and neurometabolic coupling.

Khin Khin Tha¹, Christian Stehning², Yuriko Suzuki³, Ulrich Katscher², Jochen Keupp², Ken Kazumata¹, Shunsuke Terasaka¹, Marc Van Cauteren³, Kohsuke Kudo¹, and Hiroki Shirato^1
1Hokkaido University Graduate School of Medicine, Sapporo, Japan, ²Philips Technologie GmbH, Germany, ³Philips Electronics, Japan

This study evaluated the repeatability of noninvasive electrical conductivity measurements by electric properties tomography (EPT) and the conductivity values of the normal intracranial compartments, normal-appearing brain parenchyma and intra-axial brain tumors, in 1 normal subject and 25 brain tumor patients. The results revealed high repeatability of the measurements, significantly different conductivity metrics between the tumors and adjacent normal-appearing brain parenchyma, and possible differentiation of WHO grade IV tumors from the other tumors. EPT provides information about the tissues�f electrical conductivity noninvasively and in vivo, and can become a tool for diagnosis and monitoring of the brain tumors.

Ravjit Singh Sagoo¹, David Bailey¹, Sarah Wayte², Eddie Ng'andwe¹, Charles Handford³, Sanjoy Nagaraja¹, Mahmud Saedon⁴, Helen Parsons⁵, Alex Wright^6,7, Arthur Bradwell^6,7, Christopher Imray^4,7, and Charles Hutchinson^1,8
1Department of Imaging, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom, ²Department of Medical Physics, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom, ³University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁴Department of Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom, ⁵Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, West Midlands, United Kingdom, ⁶University of Birmingham, Birmingham, United Kingdom, ⁷Birmingham Medical Research Expeditionary Society, Birmingham, United Kingdom, ⁸University of Warwick, Coventry, West Midlands, United Kingdom

One of the processes responsible for maintaining oxygen delivery in high altitude climbers is an increase in cerebral arterial flow velocity. Arterial dilatation has long thought to play no part in maintaining cerebral oxygenation, a theory that has recently been disputed. This study documents changes in middle cerebral artery (MCA) calibre, flow velocity, flow and calculated oxygen delivery in response to a 22-hour period of normobaric hypoxia in 12 subjects. MCA flow velocity significantly increased to maintain cerebral oxygen (p<0.05) while the increase in MCA calibre approached significance (p=0.09). A larger number of subjects may be needed to detect significance.

Wendy W Ni¹, Catie Chang², Hesamoddin Jahanian³, Gary H Glover³, and Greg Zaharchuk^3
1Department of Electrical Engineering, Stanford University, Stanford, CA, United States, ²Advanced MRI Section, LFMI, NINDS, NIH, Bethesda, MD, United States, ³Department of Radiology, Stanford University, Stanford, CA, United States

Cardiac contribution to resting state BOLD signal fluctuations may be modeled as a linear response to heart rate variation using the RVHR model. In this study, we interpret three features of the response function as indicators of the strength of cerebrovascular autoregulation, and examine the differences between young normals, elderly subjects with hypertension and chronic kidney disease, and elderly normals. We find statistically significant differences in response strength between young and elderly normals, and between elderly normals and patients. Our numerical results also suggest that aging reduces autoregulation, while hypertension obscures the effect of aging on BOLD signal fluctuations.

Elhum Shamshiri¹, Maria Centeno¹, Kelly St Pier², Suejen Perani¹, Helen Cross³, and David Carmichael^1
1UCL Institute of Child Health, London, UK, United Kingdom, ²Epilepsy Unit, Great Ormond Street Hospital, London, UK, United Kingdom, ³Neurosciences Unit, UCL Institute of Child Health, London, UK, United Kingdom

The current study looks at aberrant cognitive networks previously established in children with epilepsy by exploring the task-related differences between patients and controls during a ‘natural stimulus’ and resting state. We used a GLM in SPM8 as well as functional connectivity looking at temporal changes in BOLD response to analyse the results. Significant differences between groups are found in the dorsal anterior cingulate cortex. Additionally, connectivity results showed that patients recruit more brain regions than controls in performing cognitive tasks, and that patients are also shown to have problems with task switching and cognitive network modulation when compared to controls.

Jianghong He¹, Yi Zhang^1,2, Zhenyu Zhou³, Ruxiang Xu¹, and Yijun Liu^4
1Department of Neurosurgery, Beijing Army General Hospital, Beijing 100700, China, ²School of Life Science and Technology, Xidian University, Xi'an, Shanxi 710071, China, ³GE Healthcare, Beijing 100176, China, ⁴Department of Biomedical Engineering, Peking University, Beijing 100871, China

People's Republic of In disorders of consciousness (DOC), the vegetative state (VS) represents a unique mental status distinct from coma and the minimally conscious state. Functional MRI (fMRI) reveals that awareness can be reduced to two coexistent networks--- the external and internal awareness, and that the two components are anti-correlates. According to this framework, the present study hypothesizes that there is imbalance between the external and internal awareness in VS. Our study provides evidence that VS in DOC patients is likely related to the imbalance between the external and internal awareness systems as well as the DMN. The hyperactivaion of external awareness system and the hypoactive internal awareness and DMN exhibit a key pattern of brain activity in the unique mental states of VS, which may be further characterized as prognostic markers of VS and DOC.

Jianghong He¹, Yue Cui², Ming Song², Yi Zhang¹, Yuanyuan Dang¹, Tianzi Jiang², and Ruxiang Xu^1
1Department of Neurosurgery, Beijing Army General Hospital, Beijing 100700, China, ²National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China

It is generally assumed that interactions between thalamic nuclei and the cortex play an important role in consciousness. Recent studies have implicated the DMN in consciousness, which includes functional less strong connections within the DMN in patients with DOC. The purpose of the present study is to address this limitation by investigating functional connectivity between individual thalamic nuclei and the DMN in DOC patients. 9 DOC patients and 9 age-matched healthy controls were included in this study. In comparison to healthy controls, DOC patients had significantly decreased functional connectivity between the mediodorsal thalamus and brain areas within the DMN, including the medial prefrontal cortex and posterior cingulate cortex/precuneus. Patients and controls did not show differences in functional connectivity for any thalamic nucleus other than the mediodorsal thalamus.

Haiko Schlögl^1,2, Karsten Mueller¹, Annette Horstmann^1,3, Harald E Möller¹, Konstanze Miehle², Burkhard Pleger^1,4, Arno Villringer^1,4, Mathias Fasshauer^2,3, and Michael Stumvoll^2,3
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Department for Internal Medicine, University Hospital Leipzig, Germany, ³Integrated Research and Treatment Center (IFB) Adiposity Diseases, Leipzig, Germany, ⁴Day Clinic for Cognitive Neurology, University Hospital Leipzig, Germany

Patients with congenital lipodystrophy (LD) present reduced serum leptin concentrations, leading to disturbed eating behavior with the inability to develop sustaining satiety. We substituted leptin in eight LD patients and assessed functional resting state MRI during the first year of the treatment. Leptin substitution lead to decreased hunger and increased post-meal satiety. In fMRI we found a strengthened functional connectivity in dopaminergic reward regions (nucleus accumbens and medial prefrontal cortex) as well as the hedonic control centre (hypothalamus). These data suggest long-term adaptation of the interconnectedness of brain areas involved in the control eating behavior after leptin substitution in LD.

Yue Xing^1,2, Hamza Alshuft^1,2, and Dorothee Auer^1,2
1Radiological Sciences, University of Nottingham, Nottingham, United Kingdom, ²Arthritis Research UK Pain Centre, University of Nottingham, Nottinghamshire, United Kingdom

Graph theory combining MRI techniques enables a non-invasive description of structural and functional network topology in human brain. Despite the recent explosion of studies on functional brain network and anatomical connectivity provided by diffusion MRI, little is known about the structural architecture in patients with primary nociceptive disorders, which may cause reconfiguration of the underlying brain organisation. We measured cortical thickness of more precise localization of sulco-gyral regions on patients with chronic pain due to knee osteoarthritis and healthy controls. By applying graph theory analysis, we present a preliminary morphometric signature of knee osteoarthritis pain.

Ravjit Singh Sagoo¹, Victoria Bull², Helen Parsons³, Sarah Wayte⁴, Eddie Ng'andwe¹, Charles Handford⁵, Mahmud Saedon⁶, Chris Koller², Alex Wright^7,8, Arthur Bradwell^7,8, Christopher Imray^6,8, and Charles Hutchinson^1,9
1Department of Imaging, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom, ²Department of Clinical Physics and Bioengineering, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom, ³Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom, ⁴Department of Medical Physics, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom, ⁵University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁶Department of Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom, ⁷University of Birmingham, Birmingham, United Kingdom, ⁸Birmingham Medical Research Expeditionary Society, Birmingham, United Kingdom, ⁹University of Warwick, Coventry, United Kingdom

Acute mountain sickness (AMS) develops in individuals following rapid ascent to high altitudes with low atmospheric oxygen levels. One of the proposed theories is that AMS may be due to an increase in intracranial pressure as a result of cerebral oedema. Based on changes in serial apparent diffusion coefficient (ADC) maps over a 22-hour period of normobaric hypoxia, we demonstrated that ADC values were significantly higher within the corpus callosum at 11 and 22 hours compared to baseline (p<0.01), representing oedema. This change was independent of the presence of AMS. No other significant changes in cerebral ADC values were observed.

Chun-Yuan Chang^1,2, Fa-Hsuan Lin¹, and Jong-Ling Fuh^3
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Taipei, Taiwan, ²2Department of Neurology, Min-Sheng General Hospital, Taoyuan, Taiwan, Taoyuan, Taiwan, ³Neurological Institute, Taipei Veterans General Hospital, Taiwan, Taipei, Taiwan

The CKD patients had smaller total cerebral cortex volume and smaller cortical thickness compared to the control subjects. Moreover,in neurocognition test,the CKD groups showed lower scores in MMSE, MoCA and digit span forward compared with the normal control group significantly.The CKD subjects had smaller gray matter volume compared with the control subjects in some brain regions.

Ulrike Dydak^1,2, Eric J Ward³, Ruoyun Ma¹, Sandy Snyder¹, Elizabeth Zauber⁴, James B Murdoch⁵, Zaiyang Long¹, and Frank Rosenthal^1
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, ²Dept. of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³School of Health Sciences, Purdue Universiy, West Lafayette, IN, United States, ⁴Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States, ⁵Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

Thalamic GABA levels have been shown to be elevated in metal workers occupationally exposed to manganese (Mn). While symptoms of Mn neurotoxicity resemble those of Parkinson’s disease, the role of basal ganglia GABA is not clear in this context. This study finds a significant correlation between thalamic GABA levels and individual Mn exposure levels accumulated over the past three months in typically exposed welders, suggesting that GABA might serve as biomarker of recent exposure. Since the thalamus plays a major role in regulating cognitive and motor function, these findings may help to further elucidate the underlying mechanism of Mn neurotoxicity.

Zaheer Abbas¹, Kathrin Reetz^1,2, Ana Sofia Costa², Vincent Gras¹, Shahram Mirzazade^1,2, Johannes Schiefer², Georg Neuloh³, Jörg Bernhard Schulz^2,4, and N Jon Shah^1,2
1INM-4, Research Centre Jülich GmbH, Jülich, Germany, ²Department of Neurology, RWTH Aachen University, Aachen, Germany, ³Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany, ⁴Translational Brain Medicine, Jülich Aachen Research Alliance (JARA), Jülich and Aachen, Germany

Proton density (PD) is tightly regulated in the human brain. Quantitative measures of PD have provided new insights into monitoring disease progression. MRI protocols were set up to quantitatively assess PD in idiopathic normal pressure hydrocephalus (iNPH) patients, before and after cerebrospinal fluid (CSF) removal by lumbar puncture. Data were co-registered to the MNI brain template and PD mean values for total white matter (WM), total grey matter (GM), frontal, parietal, occipital and temporal WM and GM were determined. Although, no changes in GM were found, increased water content in WM (about 3%) in iNPH decreased after lumbar puncture.

Laura Biagi¹, Manuela Casarano¹, Roberta Battini¹, Tommaso Pizzorusso^2,3, Giorgio Pini⁴, Danilo Scelfo^1,5, Giovanni Cioni^1,6, and Michela Tosetti^1
1IRCCS Fondazione Stella Maris, Pisa, PI, Italy, ²Institue of Neuroscience, National Research Council, Pisa, PI, Italy, ³University of Florence, Firenze, FI, Italy, ⁴Department of Child Neurology and Psychiatry, Versilia Hospital, Lido di Camaiore, LU, Italy, ⁵Institute of Clinical Physiology, National Research Council, Pisa, PI, Italy, ⁶University of Pisa, Pisa, PI, Italy

The principal aim of this study is to identify specific biomarkers of Rett syndrome (RTT) using neuroimaging techniques that could be used as index of disease progression. 14 patients with MECP2 mutations and 14 matched healthy controls participated in the study. We explored Voxel-Based-Morphometry (VBM) and Cerebral perfusion by using pCASL technique. Data showed global reductions of GM and WM volumes in RTT patients and the capability of a functional/metabolic parameter like CBF to identify different profiles in the groups of RTT subjects, differentiating epileptic patients from no-epileptic ones and finding different alterations in patients with different respiratory patterns.

Shawna Farquharson^1,2, David Raffelt¹, Farnoosh Sadeghian¹, J-Donald Tournier^1,3, Simone Mandelstam^1,4, Michal Schneider-Kolsky², Samuel F Berkovic⁵, Ingrid Scheffer^1,5, Graeme Jackson^1,6, and Alan Connelly^1,5
1The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia, ²Department of Medical Imaging & Radiation Science, Monash University, Melbourne, Victoria, Australia, ³Deptartment of Medicine, Austin Health, University of Melbourne, Victoria, Australia, ⁴Medical Imaging, Royal Children's Hospital, Melbourne, Victoria, Australia, ⁵Department of Medicine, Austin Health, University of Melbourne, Victoria, Australia, ⁶Department of Medicine, Austin Health,University of Melbourne, Victoria, Australia

Individuals with neuronal migration disorders such as heterotopia often present with epilepsy that is refractory to medical and surgical treatment. Recent fibre tractography studies of periventricular nodular heterotopia (PVNH) patients have reported abnormal fibre tracks associated with regions of heterotopia. In the present study we use Apparent Fibre Density (AFD) to perform whole brain voxel-based analysis of DWI data from patients with PVNH to investigate differences in tissue microstructure. We observed a significant decrease in AFD in many white matter tracts beyond regions of heterotopia in PVNH patients compared to healthy control participants.

Angelique Van Ombergen¹, Ben Jeurissen², Floris Vanhevel³, Wim Van Hecke⁴, Vincent Van Rompaey⁵, Jan Sijbers², Stefan Sunaert⁶, Paul Parizel³, Paul van de Heyning⁵, and Floris Wuyts^1
1Antwerp University Research center for Equilibrium and Aerospace, University of Antwerp, Antwerp, Belgium, ²Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium, ³Department of Radiology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium, ⁴icoMetrix, Leuven, Belgium, ⁵Department of Otorhinolaryngology and Head and Neck Surgery, Antwerp University Hospital & University of Antwerp, Belgium, ⁶Department of Radiology, University Hospital of the Catholic University of Leuven, Leuven, Belgium

Correlations between diffusion and clinical vestibular parameters in uncompensated vestibular patients and healthy controls were investigated. Multi-shell high angular resolution diffusion weighted data were acquired and tractography was performed. We found multiple significant correlations between diffusion parameters in several vestibular-related brain regions and clinical parameters. Thus, this pilot study shows that quantities derived from diffusion-weighted imaging appear to be correlated with several clinical parameters from vestibular testing. This suggests that the cause of the symptoms of unresolved continuous vertigo is probably more situated at the central level than at the peripheral level.

Courtney A Bishop^1,2, Qi Guo³, Rahul Dimber¹, Rexford D Newbould^1,2, Roger N Gunn^1,2, Eugenii A Rabiner^1,3, and Graham P Taylor^4
1Imanova Centre for Imaging Sciences, London, United Kingdom, ²Department of Medicine, Imperial College London, London, United Kingdom, ³King's College London, London, United Kingdom, ⁴St Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom

HTLV1-associated myelopathy (HAM) is a chronic, debilitating neuro-inflammatory disease that may be associated with neuro-cognitive defects in spite of being a peripheral infection. In this study, we used VBM and DTI to attempt to differentiate six HAM patients (with high viral load but varying disease burden) from healthy controls, in order to probe CNS changes before the development of cognitive defects. Both VBM and DTI analysis identified the thalamus as correlated to disease burden, which was reinforced by [11C]PBR28 PET identifying the thalamus as an area of inflammation in HAM patients.

Diane Reckziegel^1,2, Jennifer Dixon^1,2, and Dorothee P. Auer^1,2
1Radiological Sciences, Division of Clinical Neurosciences, University of Nottingham, Nottingham, United Kingdom, ²Arthritis Research UK Pain Centre, Nottingham, United Kingdom

DTI was used to investigate potential brain microstructural disruptions underlying any adaptive or predisposing changes to the networks in the brain in response to chronic knee pain due to osteoarthritis (OA). TBSS and ROI-based analysis revealed an increase in thalamic MD as pain duration increases, and a tendency for association between more neuropathic-like symptoms and MD in an area involving the insula and ACC. Our findings suggest that microstructural abnormalities in OA pain, a primary nociceptive condition, are a feature of pain chronification. They seem to develop after several years of persistent pain probably preferentially in patients with more neuropathic-like symptoms.

William J Cottam^1,2, Jennifer Dixon^1,2, Laura Condon^1,2, Maryam Abaei^1,2, and Dorothee Auer^1,2
1Radiological and Imaging Sciences, Clinical Neurosciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²ARUK Pain Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

In this study we aimed to characterise the central processing of chronic knee osteoarthritis (OA) pain. We investigated the interrelations between regional cerebral blood flow (CBF) and the level of experienced spontaneous OA pain severity in chronic knee OA pain patients. Within patient analysis showed positive correlations between spontaneous pain severity (VAS scores) and local CBF within the anterior cingulate cortex, left hippocampus, left amygdala, left insula, left thalamus, left putamen, subcallosal cortex and the brain stem. In conclusion, this study shows that ASL imaging allows us to map spontaneous OA pain involving known sensory and emotional pain processing areas.

Tanja Su¹, Matthan Caan¹, Ferdinand Wit², Judith Schouten³, Gert Geurtsen³, Ben Schmand³, Frans Vos⁴, Peter Portegies⁵, Peter Reiss², and Charles Majoie^1
1Radiology, Academic Medical Center, Amsterdam, Netherlands, ²Infectious disease, Academic Medical Center, Amsterdam, Netherlands, ³Neurology, Academic Medical Center, Amsterdam, Netherlands, ⁴Delft University of Technology, Delft, Netherlands, ⁵Neurology, OLVG hospital, Amsterdam, Netherlands

HIV-associated neurocognitive disorder (HAND) has been suggested to remain common in patients with suppressed viraemia on combination antiretroviral therapy (cART). We used DTI tract-based spatial statistics (TBSS) to explore the contribution of white matter microstructural disintegration to HAND. Locally increased mean diffusivity in callosal fibers and association fibers were found in HIV-infected men on cART compared to representative uninfected controls. However, an association with cognitive impairment or impairment in any of the individually tested domains could not be demonstrated.

David Raffelt¹, Donna Parker¹, Jacinta M McMahon¹, Ingrid E Scheffer^1,2, and Alan Connelly^1,2
1Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia, ²Department of Medicine, University of Melbourne, Melbourne, VIC, Australia

Dravet syndrome is a devastating disease characterised by the onset of infantile seizures, with myoclonic, focal, and absence seizures developing later in life. Childhood development is slowed resulting in intellectual disability in most patients. Despite a well-recognised molecular etiology, little is understood about the pathophysiology. MRI abnormalities to date have been relatively sparse and not reflective of the severity of the clinical picture. We performed the first diffusion MRI study of Dravet syndrome by a whole-brain analysis of Apparent Fibre Density (AFD). We observed a marked decrease in AFD in the majority of white matter tracts compared to control participants.

Steve H Fung^1,2, Christof Karmonik^1,2, Mario F Dulay^1,2, Robert G Grossman^1,2, and Amit Verma^1,2
1Houston Methodist Research Institute, Houston, Texas, United States, ²Houston Methodist Hospital, Houston, Texas, United States

We investigated the effect of statistical threshold and various spatial masks on laterality index (LI) calculation in determining language lateralization in patients with temporal lobe epilepsy (TLE) evaluated using fMRI with language tasks. Majority of patients with TLE had some atypical lateralization, suggesting possible plasticity/reorganization of language function in patients with TLE.

Yu-Shin Ding^1,2, Bangbin Chen³, Mariana Lazar¹, Christopher Glielmi⁴, and Orrin Devinsky^5
1Radiology, New York University School of Medicine, New York, NY, United States, ²Psychiatry, New York University School of Medicine, New York, NY, United States, ³National Taiwan University Hospital, Taiwan, ⁴Siemens Healthcare, New York, NY, United States, ⁵Neurology, New York University School of Medicine, NY, United States

Surgery for treatment-resistant epilepsy can be effective, but the decision to operate depends on a careful assessment of the risk-benefit profile for each patient. A combined PET/MR scanner with simultaneous acquisition allows direct correlation of PET data with MR-detected patterns of neural synchrony in the brain, facilitating the identification of an optimal biomarker. To demonstrate this feasibility, we initiated a comparative study in controls and epilepsy patients using FDG at 7 functionally connected networks. Our results showed significant group difference in metabolism at visual and attention networks, and that ALFF at PCC significantly correlated with SUV at attention network.

Victoria L Morgan¹, Alexander S. Dagley¹, Hakmook Kang², Bassel Abou-Khalil³, and Baxter P. Rogers^1
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, United States, ²Biostatistics, Vanderbilt University, Tennessee, United States,³Neurology, Vanderbilt University, Tennessee, United States

We used elastic net linear regression to identify regional structural and functional parameters that predict duration of temporal lobe epilepsy to quantify the evolution of the disease. We found that the volume of regions including the thalamus, putamen, entorhinal cortex and the hippocampus decrease linearly as duration increases. Functional connectivity between many regions including the left hippocampus and the right insula, left and right insula, and the right hippocampus and the left thalamus also vary linearly as duration of disease increases. The identification of this network can inform decisions on surgical treatment and prediction of surgical outcome.

Daniel Rodriguez¹, Nigel P Davies^2,3, L Abernethy⁴, Chris A Clark^5,6, Tim Jaspan⁷, D Hargrave⁶, L MacPherson³, Martin O Leach⁸, G S Payne⁸, B L Pizer⁴, Andrew C Peet^2,9, T Arvanitis^9,10, Richard Grundy^1,7, and Dorothee P Auer^1,7
1University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²University of Birmingham, Birmingham, United Kingdom, ³University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁴Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom, ⁵University College London, London, United Kingdom,⁶Great Ormond Street Hospital, London, United Kingdom, ⁷Nottingham University Hospitals Trust, Nottingham, United Kingdom, ⁸The Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom, ⁹Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, United Kingdom, ¹⁰University of Warwick, Coventry, United Kingdom

The relationship between ADC histogram-based metrics and neurofibromatosis type1 (NF1) in optic pathway gliomas (OPG) is investigated. Non-NF1 OPGs are known to carry a significantly poorer prognosis without any differences in conventional MR imaging markers. This study suggests that there are no differences in ADC-based metrics between NF1 groups either.

Shih-Wei Chiang^1,2, Cheng-Yu Chen^3,4, Ping-Huei Tsai³, Hsiao-Wen Chung¹, Chao-Ying Wang², and Ming-Chung Chou^5
1Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ²Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taipei, Taiwan, ³Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ⁴Institue of Clinical Medicine, Taipei Medical University, Taipei, Taiwan, ⁵Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan

Gait disturbance in iNPH is associatedwith altered axonal integrity in the corups callosum and lower-limb motortracts. The degree of axonal integrity changes is significantly increased inlumbar-drainage non-responders than the responders. DTI may potentially beuseful in differentiate the responders from non-responders in the diagnosticworkup of iNPH patients who might benefit fronm permanent ventriculo-peritonealshunting treatment.

Arturo Cardenas-Blanco¹, Judith Machts², Julio Acosta-Cabronero¹, Joern Kaufmann², Susanne Abdulla³, Katja Kollewe³, Susanne Petri³, Reinhard Dengler³, Stefan Vielhaber², and Peter Nestor^1
1Brain Plasticity & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Saxony-Anhalt, Germany, ²Neurology, Magdeburg medical school, Magdeburg, Germany, ³Neurology, Hannover medical school, Hannover, Germany

Bulbar onset amyotrophic lateral sclerosis (ALS-B) has a worse prognosis that limb onset (ALS-L). This could reflect either that ALS-B targets muscles more critical for survival or because it is biologically more aggressive. The purpose of this study was to compare patterns of neuro-degeneration between ALS-B and ALS-L patients carefully matching age, sex, cognitive impairment and motor dysfunction using DTI. The results indicated that both groups had similar distribution of change (corticospinal tracts) although ALS-B had more severe white matter tract degeneration than ALS-L. This suggests that, when matched for clinical markers of severity, ALS-B is a more aggressive variant.

Joao M. S. Pereira¹, Julio Acosta-Cabronero², Peter J. Nestor², Guy B. Williams³, and Miguel Castelo-Branco^4
1Laboratory of Biostatistics, IBILI - Faculty of Medicine, University of Coimbra, Coimbra, Portugal, ²German Centre for Neurodegenerative Diseases (DZNE), Magdeburg, Germany, ³Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ⁴Visual Sciences Laboratory, IBILI - Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Voxel based morphometry (VBM) is a common brain imaging tool used in research to detect differences in the volume of brain tissues between groups. Its application to a clinical setting has been hampered by its inability to assess single subjects. This work presents a proof of concept of single subject VBM, using a nonlinear registration algorithm to simulate normal anatomical variability and thus generate a sample of subjects out of a single scan.

Guangwei Du¹, Tian Liu², Mechelle M. Lewis^1,3, Jeffrey Vesek⁴, Lan Kong⁵, Martin Styner⁶, Qing X. Yang^4,7, and Xuemei Huang^1,4
1Department of Neurology, Penn State Hershey Medical Center, Hershey, PA, United States, ²MedImageMetric LLC, New York, NY, United States, ³Department of Pharmacology, Penn State Hershey Medical Center, Hershey, PA, United States, ⁴Department of Radiology, Penn State Hershey Medical Center, Hershey, PA, United States,⁵Public Health Sciences, Penn State Hershey Medical Center, Hershey, PA, United States, ⁶Department of Computer Science, University of North Carolina, Chapel Hill, NC, United States, ⁷Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Increased iron content in the substantia nigra (SN) of PD patients has been reported as a surrogate marker of PD. Quantitative susceptibility mapping (QSM) has been proposed to directly quantify iron content in human brain. In this work, we examine the use of QSM as an in vivo marker(s) of PD related pathology in nigrastriatal structures. Our results showed increased susceptibility in the SN and the RN in PD patients compared with controls. This study supports the hypothesis that QSM can measure iron accumulation associated with the PD-related pathological process.

Yu-Shin Ding^1,2, Bangbin Chen³, Christopher Glielmi⁴, Timothy Shepherd¹, Thomas Koesters¹, Anne-Kristin Vahle¹, Kent Friedman¹, Fernando Boada¹, and Orrin Devinsky^5
1Radiology, New York University School of Medicine, New York, NY, United States, ²Psychiatry, New York University School of Medicine, New York, NY, United States, ³Medical Imaging, National Taiwan University Hospital, Taiwan, ⁴Siemens Healthcare, NY, United States, ⁵Neurology, New York University School of Medicine, NY, United States

We have initiated a comparative study in neurotypical controls (NC) and epilepsy patients (Epi) using a state-of-the-art PET/MR combined imaging technology with simultaneous acquisition to study epilepsy. With quantitative data analysis on glucose metabolism in over 120 brain regions, we have identified the ROIs showed group differences. The fact that our preliminary results (e.g., abnormal regional glucose metabolism and prevalence of asymmetry) are consistent with the clinical data of epilepsy patients suggests that simultaneous PET/MR imaging provides a useful imaging tool to identify regional abnormality and assist in localizing the seizure focus.

Katherine A Koenig¹, Mark J Lowe¹, Jian Lin¹, Deborah L Harrington², Ken E Sakaie¹, Jane S Paulsen³, and Stephen M Rao^4
1Imaging Sciences, The Cleveland Clinic, Cleveland, OH, United States, ²Research, Neurology, and Radiology Services, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States, ³Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, Iowa, United States, ⁴Neurological Institute, The Cleveland Clinic, Cleveland, OH, United States

Activation on a motor task was used to seed a resting state connectivity analysis in the left primary motor cortex (M1) in 48 participants in the prodromal stages of Huntington’s disease (preHD) and 16 gene-negative participants. Bilateral anterior cerebellar lobes and bilateral middle temporal gyri showed a relationship between strength of connectivity to left M1 and time-to-onset in preHD. These findings suggest that connectivity strength is impacted by disease process prior to onset of symptoms in HD.

Thibo Billiet^1,2, Sabine Deprez^1,2, Burkhard Maedler³, Ronald Peeters^1,2, Hui Zhang⁴, Alexander Leemans⁵, Thijs Dhollander⁶, Daan Christiaens⁶, Frederic Amant⁷, Ann Smeets⁷, Bea Van den Bergh⁸, Mathieu Vandenbulcke⁹, Eric Legius¹⁰, Stefan Sunaert^1,2, and Louise Emsell^1,2
1Translational MRI, Imaging & Pathology, KU Leuven & Radiology, University Hospitals Leuven, Leuven, Belgium, ²Medical Imaging Research Center, Leuven, Belgium,³Stereotaxis and MR-based Intervention, Department of Neurosurgery, Bonn University Hospital, Bonn, Germany, ⁴Computer Science, University College London, London, United Kingdom, ⁵University Medical Center, Utrecht, Netherlands, ⁶ESAT-PSI Processing Speech and Images, KU Leuven, Leuven, Belgium, ⁷Leuven Cancer Institute (LKI), Multidisciplinary Breast Cancer Unit, KU Leuven & University Hospitals Leuven, Belgium, ⁸Developmental Psychology, Tilburg University, Tilburg, Netherlands, ⁹Psychiatry, KU Leuven & University Hospitals Leuven, Leuven, Belgium, ¹⁰Human Genetics, KU Leuven & University Hospitals Leuven, Leuven, Belgium

Systemic chemotherapy as a treatment against breast cancer patients is known to induce cognitive deficits, related with alterations in diffusion tensor imaging (DTI) measures of the brain's white matter. Using advanced diffusion techiques (DTI, DKI, NODDI) and multicomponent T2 relaxation, the long-term effects of this chemotherapy treatment are assessed.

Hiroshi Kawaguchi¹, Hitoshi Shimada¹, Masayuki Suzuki¹, Shigeki Hirano¹, Hitoshi Shinotoh¹, Jeff Kershaw¹, Tetsuya Suhara¹, and Hiroshi Ito^1
1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba, Japan

Ying Cui¹, Yun Jiao¹, Pei-Cheng Li¹, Bing Luo¹, Hai-Dong Zhu¹, Cheng-yu Peng¹, and Gao-Jun Teng^1
1Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospita, Nanjing, Jiangsu, China

Type 2 diabetes mellitus (T2DM) has been shown to be associated with an increased risk of dementia. However, the etiology underlying is still largely unknown. The default-mode network (DMN) is an important brain network which supports several key functions. Dysfunction of DMN has been suggested as an early marker of several psychiatric disorders. This study aimed to investigate the integrity of the DMN by using independent component analysis (ICA) in T2DM patients and to correlate the DMN functional connectivity (FC) changes with neurocognitive performance and clinical variables. The disrupted DMN could help imply the mechanism linking T2DM and cognitive impairment.

David Neil Manners¹, Giovanni Rizzo^1,2, Chiara La Morgia^1,2, Caterina Tonon¹, Claudia Testa¹, Piero Barboni³, Emil Malucelli⁴, Maria Lucia Valentino^1,2, Leonardo Caporali^1,2, Daniela Strobbe^1,2, Valerio Carelli^1,2, and Raffaele Lodi^1
1Dept of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Emilia Romagna, Italy, ²IRCCS Istituto delle Scienze Neurologiche di Bologna, Emilia Romagna, Italy, ³Studio Occulistico d'Azeglio, Bologna, Italy, ⁴Dept of Pharmacy and Biotechnology, University of Bologna, Bologna, Emilia Romagna, Italy

Whole brain white matter of 19 OPA1-dominant optic atrophy (OPA1-DOA) patients was compared with 17 Leber's hereditary optic atrophy (LHON) patients and 19 healthy controls, using diffusion tensor imaging, to detect subtle structural alterations. LHON patients presented a preferential involvement of the optic radiation and of the acoustic radiation possibly due to trans-synaptic degeneration, with a protective effect of idebenone therapy. OPA1-DOA patients presented a widespread involvement supporting the view of a multisystemic disorder. The correlation between diffusivity abnormalities and the age of these patients also supports the hypothesis of a congenital and developmental disorder

Thibo Billiet^1,2, Sabine Deprez^1,2, Burkhard Maedler³, Felice D'Arco⁴, Ellen Plasschaert⁵, Ronald Peeters^1,2, Hui Zhang⁶, Alexander Leemans⁷, Bea Van den Bergh⁸, Mathieu Vandenbulcke⁹, Eric Legius⁵, Stefan Sunaert^1,2, and Louise Emsell^1,2
1Translational MRI, Imaging & Pathology, KU Leuven & Radiology, University Hospitals Leuven, Leuven, Belgium, ²Medical Imaging Research Center, Leuven, Belgium,³Stereotaxis and MR-based Intervention, Department of Neurosurgery, Bonn University Hospital, Bonn, Germany, ⁴Diagnostic Imaging and Radiotherapy, University Federico II of Naples, Salerno, Italy, ⁵Human Genetics, KU Leuven & University Hospitals Leuven, Leuven, Belgium, ⁶Computer Science, University College London, London, United Kingdom, ⁷University Medical Center, Utrecht, Netherlands, ⁸Developmental Psychology, Tilburg University, Tilburg, Netherlands, ⁹Psychiatry, KU Leuven & University Hospitals Leuven, Leuven, Belgium

Often Neurofibromatosis type 1 (NF1) patients express hyperintensities on T2-weighted MRI brain scans. Their microstructure is still not well understood. Combining multicomponent T2 relaxation and advanced diffusion techniques (DTI, DKI, NODDI) we try to characterize these so-called "unidentified bright objects" (UBOs)

Paula Trujillo^1,2, Paul Summers¹, Giorgio Marotta³, Ioannis Isaias^4,5, and Antonella Costa^1
1Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI, Italy, ²Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, MI, Italy, ³Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI, Italy, ⁴Centro Parkinson, Istituti Clinici di Perfezionamento, Milan, MI, Italy, ⁵Neurologische Klinik und Poliklinik, Universitätsklinikum Würzburg, Bayern, Germany

Our aim was to compare contrast-to-noise ratio (CNR) and volume measurements of the substantia nigra (SN) made using NM-MRI with dopamine reuptake in the caudate nucleus and putamen in Parkinson’s disease patients as measured using FP-CIT SPECT. Differences in NM-MRI measures between healthy controls (HC) and Parkinson’s disease (PD) patients were also examined. Both NM-MRI measures of the SN showed a significant correlation with the FP-CIT binding values, and were significantly different between the HC and PD groups. Our results suggest that NM-MRI may find use in quantifying pathology and following disease progression.

João M. Sousa^1,2, Rita G. Nunes¹, Sofia Reimão³, Joaquim Ferreira⁴, and Hugo A. Ferreira^1
1IBEB - Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal, ²FCT - NOVA University of Lisbon, Almada, Setubal, Portugal, ³Neurologial Imaging Department, Centro Hospitalar Lisboa Norte - Hospital de Santa Maria, Lisbon, Portugal, ⁴Clinical Pharmacology Unit, Instituto de Medicina Molecular and Laboratory of Clinical Pharmacology, Lisbon, Portugal

In this work we compared structural connectivity metrics derived from diffusion data of Parkinson’s Disease (PD) subjects and a control group. As well as standard analysis of Fractional Anisotropy (FA) and Mean Diffusivity (MD) Diffusion Tensor measures, Graph Theory (GT) analysis was employed. Detected differences in FA and MD were consistent with previous work, while connectivity metrics derived from GT were able to detect significant changes in further areas also known to be involved in PD. A new framework for exploring connectivity metrics as biomarkers for PD has been proposed which may offer novel insights into the disease.

Jessica J Steventon^1,2, Da Ma^3,4, Manual J Cardoso⁴, Marc Modat⁴, Mark F Lythgoe^3,4, Sebastian Ourselin⁴, Rebecca Trueman^2,5, Anne E Rosser², and Derek K Jones^1
1Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff, Wales, United Kingdom, ²Brain Repair Group, Cardiff University, Cardiff, Wales, United Kingdom, ³Centre for Advanced Biomedical Imaging (CABI), University College London, London, United Kingdom, ⁴Centre for Medical Image Computing (CMIC), University College London, London, United Kingdom, ⁵Nottingham University, Nottingham, United Kingdom

Patient studies in Huntington’s Disease (HD) are limited by the incompatibility of MRI with chorea, producing an incomplete picture of neuropathological changes at later disease stages. Here, we used both T2-weighted and diffusion MRI in a mouse model of HD at a pre-symptomatic and symptomatic time-point, where anaesthesia is necessary during scanning but eliminates chorea-related motion artefacts. We apply automated atlas-based segmentation and diffusion tractography for the first time in a knock-in mouse model of HD and find that macro-structural changes preceded micro-structural changes, suggesting microstructural abnormalities may be a downstream effect of grey matter abnormalities in HD.

Florian Franz Erich Borsodi¹, Christian Langkammer¹, Valeriu Culea¹, Lukas Pirpamer¹, Christian Enzinger^1,2, Reinhold Schmidt¹, Franz Fazekas¹, and Stefan Ropele^1
1Department of Neurology, Medical University of Graz, Graz, Austria, ²Division of Neuroradiology, Medical University of Graz, Graz, Austria

Previous approaches to study microstructural tissue changes in the corticospinal tract (CST) of patients suffering from amyotrophic lateral sclerosis (ALS) were based on spatial statistics on a group level with its inherent limitations. In our research, we applied a new global probabilistic fiber tracking approach with an automated seed region positioning to study diffusion properties (FA, MD, RD, AD) in major white-matter tracts of 23 ALS patients and 18 age-matched healthy controls. In line with previous studies, we found significant changes in the CST, while other tracts remained unaffected.

David Neil Manners¹, Emil Malucelli², Giuseppe Nicoletti³, Claudia Testa¹, Caterina Tonon¹, Aldo Quattrone³, and Raffaele Lodi^1
1Dept of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Emilia Romagna, Italy, ²Dept of Pharmacy and Biotechnology, University of Bologna, Bologna, Emilia Romagna, Italy, ³National Research Council Neuroimaging Research Unit, University Magna Graecia, Catanzaro, Calabria, Italy

A voxel-based morphometry analysis was conducted on isotropic T1-weighted brain image volumes, acquired at 1.5 T, to determine whether variations in the APOE allele, known as a risk factor in disorders such as Alzheimer’s disease, are also associated with grey matter degenerative changes in patients with Parkinson’s disease (PD), with or without dementia. Despite a small increase in whole brain CSF in patients with the ε4 allele, after accounting for age, brain size and dementia, no localized grey matter changes were detected. Variations in the APOE allele are not associated with grey matter degenerative changes in the PD patients studied.

Lele Xu¹, Xia Wu^1,2, and Li Yao^1,2
1School of Information Science and Technology, Beijing Normal University, Beijing, Beijing, China, ²State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, Beijing, China

In this study, the group ICA and correlation analysis methods were performed to explore and compare the network coupling in the triple networks, including the salience network (SN), executive control network (ECN) and default mode network (DMN), for Parkinson¡¯s disease (PD) patients and normal controls. The results revealed decreased coupling between SN and ECN for PD patients, suggesting that SN may less focus on the processing of external stimuli for PD patients. Furthermore, the results also showed the decreased coupling between SN and DMN, indicating that for PD patients, SN may also less mediate the processing of internal events.

Pi-Yu Hsu^1,2, Chou-Ming Cheng², Chi-Che Chou², Li-Kai Cheng¹, and Tzu-Chen Yeh^1,3
1Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, ²Integrated Brain Research Unit, Taipei Veterans General Hospital, Taipei, Taiwan, ³Department of radiology, Taipei Veterans General Hospital, Taipei, Taiwan

This study was compared with single- and multi-modal voxel-based morphometry database approach to detect the lesion of focal cortical dysplasia (FCD). The approaches used to assist or remind neuroradiologist for detecting the potential lesion of FCD.

Matthew C. Murphy^1,2, Ian P. Conner¹, Seong-Gi Kim^2,3, Gadi Wollstein¹, Joel S. Schuman¹, and Kevin C. Chan^1,2
1Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, United States, ²Neuroimaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ³Center for Neuroscience Imaging Research, Department of Biological Sciences, SKKU, Suwon, Korea

Glaucoma is a neurodegenerative disease that affects the entire visual system, from eye to visual cortex. However, the pathogenesis of glaucoma in the human visual brain and its relationship with progression in the eye remains largely unknown. The purpose of this study was to assess that relationship in a group of 22 subjects spanning the spectrum of glaucoma severity. The results indicate a significant relationship between disease severity (as assessed by both clinical diagnosis and ocular structural measurements) and measures of brain function (measured by BOLD response to visual stimulation) and metabolism (measured by proton MRS in the visual cortex).

Jack A Wells¹, James M O'Callaghan¹, Holly E Holmes¹, Nicholas M Powell¹, Bernard Siow¹, F Torrealdea², Marilena Rega², Ozama Ismail¹, Simon Walker-Samuel¹, Xavier Golay², Simon Richardson¹, Adam J Schwarz³, Michael J O'Neil⁴, Emily C Collins³, Niall Colgan¹, and Mark F Lythgoe^1
1Centre for Advanced Biomedical Imaging, UCL, London, London, United Kingdom, ²Institute of Neurology, UCL, London, United Kingdom, ³Lilly Corporate Centre, Eli Lilly & Co. Ltd, Indianapolis, United States, ⁴Eli Lilly & Co. Ltd Erl Wood Manor, Windlesham, Surrey, United Kingdom

In this study, we target diverse and specific components of tau pathology by applying multi-parametric MRI to the rTg4510 model of Alzheimer’s disease. We investigate how elevated tau expression affects: i) cerebral blood flow using arterial spin labelling ii) chemical exchange saturation transfer iii) brain glucose uptake using gluco-CEST iv) diffusion tensor imaging and v) brain atrophy using tensor based morphometry. Each technique can unambiguously discriminate tau pathology from healthy control subjects in selective white and grey matter regions, providing a platform for the longitudinal assessment of experimental treatments using non-invasive imaging techniques.

Mark David Meadowcroft^1,2, Douglas G Peters¹, Carson Purnell², James R Connor¹, and Qing X Yang^1,2
1Neurosurgery, The Pennsylvania State University - College of Medicine, Hershey, PA, United States, ²Radiology, The Pennsylvania State University - College of Medicine, Hershey, PA, United States

The role of iron in the formation of amyloid-beta plaques and neurofibrillary-tangles in not well understood. Our research has shown that the APP/PS1 transgenic mouse model produces plaques in a light iron environment compared to Alzheimer’s disease. Furthermore, transgenic model plaques exhibit dissimilar plaque morphology, inflammatory response, and have less focal iron. The goal of this study is to recapitulate the Alzheimer’s neuronal milieu through diet induced iron over-loading with a novel lipophilic compound and evaluate the role of iron on Alzheimer’s disease pathology. The results show longitudinal changes in regional transverse relaxation indicative of iron loading and plaque progression.

Elena Makovac¹, Laura Serra¹, Barbara Spanò¹, Giovanni Giulietti¹, Mario Torso¹, Mara Cercignani^1,2, Carlo Caltagirone^3,4, and Marco Bozzali^5
1Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy, ²Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, United Kingdom, ³Deptment of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy, ⁴University of Rome ‘Tor Vergata’, Rome, Italy, ⁵Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Italy

Behavioral disorders and psychological symptoms (BPSD) in Alzheimer’s Disease (AD) are known to correlate both with grey matter (GM) atrophy and white matter (WM) damage. Using probabilistic tractography and voxel based morphometry of the GM we were able to delineate precise patterns of correlation between WM damage in the Genu of the Corpus Callosum and GM atrophy in AD patients exhibiting four different BPSD clusters: mood alterations, frontal deficits, psychosis and apathy. Our data shows that BPSD are likely to be caused by a disconnection syndrome, rather than being a reactive response to accumulation of cognitive disabilities.

Hui Zhang¹, Ying Hao¹, Brad Manor^1,2, Jue Zhang^1,3, Jing Fang^1,3, and Vera Novak^4
1Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, Beijing, China, ²Division of Gerontology, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, United States, ³College of Enigneering, Peking University, Beijing, Beijing, China, ⁴Department of Neurology, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, United States

Type 2 Diabetes mellitus (T2DM) is a major risk factor for cognitive impairment, vascular dementia and Alzheimer¡¯s disease (AD). It accelerates brain aging, leads to insulin resistance, and insulin transport. Intranasal insulin (INI) administration improved cognition and memory in healthy young and older people, but also in patients with cognitive impairment or mild AD. The mechanism for INI-related improvement of memory (hippocampus function) remains unclear. In our research, resting state fMRI was used to study connectivity between hippocampus and default mode network (DMN) after the administration of intranasal insulin or placebo in type 2 DM and controls adults.

Jeff Thompson^1,2, Kevin Whittingstall³, Nicolas Vigneau-Roy^3,4, Mohammed A. Warsi⁵, and Michael D. Noseworthy^1,2
1Electrical and Computer Engineering, McMaster University, Hamilton, Ontario, Canada, ²Imaging Research Centre, St. Joseph's Healthcare, Hamilton, Ontario, Canada,³Department of Diagnostic Radiology, Sherbrooke University, Sherbrooke, Quebec, Canada, ⁴Molecular Imaging Centre, Sherbrooke University, Sherbrooke, Quebec, Canada,⁵Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada

Using Susceptibility Weighted Magnetic Resonance Imaging, a significant increase in venous density was found in subjects with Alzheimer’s Disease (AD). This study used 37 suspected AD subjects and 16 healthy age-matched controls. The venous density was found for the whole brain, as well as the grey matter and white matter. The subjects brains were registered to an AD atlas and statistical testing was performed showing the brain regions of greatest venous difference.

Christos Michaelides¹, David J Lythgoe¹, Harold G Parkes², Claire Troakes³, Istvan Bodi⁴, Tina Geraki⁵, Amy H Herlihy⁶, and Po-Wah So^1
1Department of Neuroimaging, Institute of Psychiatry, King's College London, London, London, United Kingdom, ²CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, United Kingdom, ³MRC London Neurodegenerative Diseases Brain Bank, Department of Clinical Neuroscience, Institute of Psychiatry, King’s College London, London, United Kingdom, ⁴Clinical Neuropathology & London Neurodegenerative Diseases Brain Bank, King's College London, King’s College Hospital, London, United Kingdom, ⁵Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, United Kingdom, ⁶Agilent Technologies, Yarnton, Oxfordshire, United Kingdom

Iron dysregulation may be a contributing factor to neuronal cell death in Alzheimer’s disease. MR relaxometry measurements in fixed post-mortem human AD and control samples were correlated with direct iron assessment by synchrotron-radiation X-ray fluorescence mapping. AD did not affect iron concentrations or relaxometry. Whilst R2 and R2* correlated with iron, R1 correlated less well, potentially due to significant effects from fixation time. Increased iron in white compared to grey matter is consistent with elevated iron concentrations within white matter myelin. Our results support R2 and R2* relaxometry in non-invasive assessment of brain iron.

Mathijs Buijs¹, Sanneke van Rooden¹, Maarten Versluis¹, Andrew Webb¹, Mark van Buchem¹, and Jeroen van der Grond^1
1Radiology, Leiden University Medical Center, Leiden, Netherlands

Subjective cognitive impairment can be prodromal to Alzheimer's disease. Alzheimer-related pathology has been known to precede symptoms by as much as two decades. Using 7 Tesla MRI, cortical Alzheimer-related phase shifts can be visualized. We investigated whether these phase shifts could be detected in SCI, and whether there is a correlation between phase shifts and cognitive performance. We found significant correlations between measured cortical phase shifts and neuropsychological test scores. In subjects with SCI no AD-like phase shifts could be determined.

Elena Makovac¹, Laura Serra¹, Barbara Spanò¹, Giovanni Giulietti¹, Mario Torso¹, Mara Cercignani^1,2, Carlo Caltagirone^3,4, and Marco Bozzali^1
1Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy, ²Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, United Kingdom, ³Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy, ⁴Department of Neuroscience, University of Rome ‘Tor Vergata’, Italy

Patients with amnestic mild cognitive impairment (aMCI) are known to have a higher risk of convertion to AD than healthy elderly subjects. In this longitudinal study, we used probabilistic tractography to perform a multiple DTI index analysis of the principal association, limbic and commissural WM tracts known to be involved by AD pathology. Subtle changes in brain structure associated with disease progression were remarkably more evident in aMCI converters than MCI non converters. These findings suggest that both primary myelin breakdown and axonal loss occur over AD evolution, and different patterns may account for different stages between preclinical and clinical AD.

Matthias Vandesquille^1,2, Chrystelle Po^1,2, Mathieu Santin^1,3, Emmanuel Comoy⁴, and Marc Dhenain^1
1MIRCen, CEA, Fontenay-aux-Roses, France, ²Institut Pasteur, Paris, France, ³ICM, Hôpital de la Pitié Salpêtrière, Paris, France, ⁴SEPIA, CEA, Fontenay-aux-Roses, France

Amyloid plaques are one of the hallmarks of Alzheimer’s disease and numerous mouse models of amyloidosis have been developed to study the pathology. In APP_sl/PS1_M146Lmice amyloid plaques can be detected by in vivo MRI thanks to gadolinium-staining procedure, a method based on the intravenous or intracerebroventricular administration of gadolinium contrast agent to the mice. The present work evaluated gadolinium-staining procedure to compare the in vivo and ex vivo MRI detection of amyloid plaques in five different mouse strains developing amyloidosis. Depending on the strain, the number, the size and the contrast of the plaques are highly different.

Michael Horn¹, Nyoman Kurniawan², Marianne D Keller², Ian M Brereton², and Graham J Galloway^2
1University of Melbourne, Melbourne, Victoria, Australia, ²Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia

Automated detection of amyloid plaques and microbleeds visualised using MRI phase image and susceptibility weighted imaging (SWI) acquired using an ultra-high field magnet will be demonstrated. We hypothesised that the phase shifts between amyloid plaques and microbleeds are significantly distinct, and therefore fine-tuning the weighting of the phase map for creating SWI could help distinguishing microbleeds from plaques. The validity of this methodology will be assessed using a fixed brain from an APP23 mouse model of Alzheimers Dementia.

Michael Dayan¹, Farras Abdelnour¹, Eve LoCastro¹, Amy Kuceyeski¹, Sneha Pandya¹, and Ashish Raj^1
1Department of Radiology, Weill Cornell Medical College, New York, NY, United States

The origin and course of Alzheimer's Disease (AD) was estimated with a diffusion model propagating on a network. The network nodes were defined in 73 healthy controls as 90 different cerebral regions and its edges as the connectivity strength between these regions, as estimated from diffusion imaging and tractography. The atrophy pattern in AD patients was estimated from a two sample t-test between 99 AD subjects and 95 age-matched controls. AD foci were estimated by seeding the diffusion model in all regions in turn and calculating the maximum correlation over time with the observed atrophy pattern. The most likely foci were found to be the hippocampus, caudate, putamen and amygdala. When seeding from the hippocampus, the AD progression calculated from the model was similar to the known time course of AD.

Aikaterini Kotrotsou¹, David A. Bennett², Julie A. Schneider², Sue E. Leurgans², and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States

The purpose of this study was to investigate the link between the total volume of brain white matter hyperintensities (WMH) and various age-related neuropathologies, in a community cohort of 264 older persons. WMH volume was measured with ex-vivo MRI on brain hemispheres from all participants. It was demonstrated that the total WMH volume was significantly associated with AD pathology and gross chronic infarcts. To our knowledge, this study is the largest MRI-pathology investigation of WMHs in a community cohort to date.

Flavio Dell'Acqua^1,2, Wasim Khan^1,2, David Bouls¹, Gareth J Barker¹, Gunther Schumann^2,3, Simon Lovestone^2,4, and Andrew Simmons^1,2
1Neuroimaging, King's College London, Institute of Psychiatry, London, United Kingdom, ²NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia, King's College London, Institute of Psychiatry, London, United Kingdom, ³Social, Genetic and Developmental Psychiatry Centre, King's College London, Institute of Psychiatry, London, United Kingdom, ⁴Old Age Psychiatry, King's College London, Institute of Psychiatry, London, United Kingdom

Alleles of the Apolipoprotein E (ApoE) gene are known to modulate the genetic risk for developing late-onset Alzheimer’s disease (AD). While the presence of ApoE ε4 allele is a major genetic risk factor for the development of late onset AD, the possession of the ε2 allele has been suggested to confer a protective effect against the disease. On a cohort of more than 500 young healthy adolescents this TBSS study found no differences in white matter microstructural organisation between carriers and non-carriers of the ApoE ε4 and ε2 alleles suggesting that effects of these alleles may emerge later in life.

Anne Rijpma^1,2, Marinette van der Graaf^3,4, Olga Meulenbroek^1,2, Rianne de Heus¹, Marcel G.M. Olde Rikkert^1,2, and Arend Heerschap^3
1Geriatric Medicine, Radboud university medical center, Nijmegen, Gelderland, Netherlands, ²Radboud Alzheimer Centre, Radboud university medical center, Nijmegen, Gelderland, Netherlands, ³Radiology, Radboud university medical center, Nijmegen, Gelderland, Netherlands, ⁴Paediatrics, Radboud university medical center, Nijmegen, Gelderland, Netherlands

3D ³¹P-MRSI was performed to assess whether regional variation could be observed in phospholipid and energy metabolism in 17 patients with mild Alzheimer Disease (AD). The results showed significantly (P<.01) higher PE and PC content for anterior cingulate cortex (ACC) than for retrospinal cortex (RSC). In addition, differences in high energy phosphates were found, with high Pi and NAD, low PCr and ATP for the ACC, and high PCr, low ATP, Pi and NAD for the RSC, both compared with contents obtained in the hippocampi. These variations indicate regional differences in phosphorus metabolism in the mild AD brain.

Niall Colgan*¹, Bernard Siow*^1,2, James M O'Callaghan¹, Jack A Wells¹, Holly E Holmes¹, Nick M Powell^1,2, Ozama Ismail¹, Simon Richardson^1,2, Daniel C Alexander², Emily C Collins³, Michael O'Neill⁴, Hui Zhang*², and Mark F Lythgoe*^1
1Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, ²Centre for Medical Image Computing, University College London, London, United Kingdom, ³Eli Lilly and Company, Indianapolis, United States, ⁴Eli Lilly & Co. Ltd, Surrey, United Kingdom

We applied neurite orientation dispersion and density imaging (NODDI) to estimate the microstructural changes due to tau pathology in the TG4510 (TG) animal model of Alzheimer’s disease (AD). The mouse model overexpresses a mutant human tau (P301L) resulting in intercellular tauopathies largely restricted to the hippocampus, cortex, olfactory bulb, and striatum. NODDI metrics discriminated between the wild type (WT) and TG is distinct regions of the brain associated with pathology.

Leonardo A. Rivera-Rivera¹, Eric M. Schrauben¹, Sterling C. Johnson², Kevin M. Johnson¹, Michael Loecher¹, Patrick Turski², Chuck Illingworth², and Oliver Wieben^1,3
1Medical Physics, University of Wisconsin, Madison, Wisconsin, United States, ²Medicine, University of Wisconsin, Madison, Wisconsin, United States, ³Radiology, University of Wisconsin, Madison, Wisconsin, United States

Cerebral arteries are often morphologically altered and dysfunctional in Alzheimer’s disease. In this pilot study, 4D flow MRI was used to measure intra-cranial flow features, particularly mean flow and pulsatility index, in patients with AD and in healthy controls. We found a statistically significant decrease in mean flow and increase in pulsatility index for the AD patients. With the large volume coverage and high temporal and spatial resolution demonstrated here, 4D flow MRI can provide additional biomarkers of vascular health that can contribute to the identifying patients who could benefit from interventions to improve circulatory system functions.

Susanne J. van Veluw¹, Jaco J.M. Zwanenburg², Wim G.M. Spliet³, Peter R. Luijten², and Geert Jan Biessels^1
1Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands, ²Radiology, University Medical Center Utrecht, Utrecht, Netherlands,³Pathology, University Medical Center Utrecht, Utrecht, Netherlands

Cerebral microinfarcts are common neuropathological findings in the aging human brain, and correlate strongly with cognitive decline. Post-mortem brain MRI at high field strength (7Tesla) has proven to be useful in identifying microinfarcts and to translate findings to in vivo. In the current study, we have used post-mortem 7Tesla MRI to characterise microinfarct subtypes. By using a targeted approach, 4 types of intracortical microinfarcts could be identified. Future studies can now look into the causes of these abundant manifestations of small vessel disease to better understand their role in aging and dementia.

Bernd Merkel^1,2, Nicola T. Lautenschlager³, Kay Cox⁴, David Ames^2,5, Kathryn A. Ellis³, Elizabeth Cyarto⁵, Pramit Phal¹, Bob Tran², Christopher Steward^1,2, and Patricia M. Desmond^1,2
1Radiology, Royal Melbourne Hospital, Parkville, VIC, Australia, ²The University of Melbourne, VIC, Australia, ³Psychiatry, The University of Melbourne, VIC, Australia,⁴University of Western Australia, Perth, Western Australia, Australia, ⁵National Ageing Research Institute, Parkville, VIC, Australia

White matter hyperintensities (WMH), which appear bright on T2-FLAIR images, are considered to reflect pathology of brain vessels and have been linked to age-related cognitive changes as well as cognitive impairments and complaints. Physical activity (PA) may be a modifiable and potentially protective factor for Alzheimer’s Disease (AD). However, its effect on cerebrovascular disease and AD is still not clear. We segmented and quantified WMH and hippocampal volumes of patients with subjective memory complaints (SMC) and mild cognitive impairments (MCI), who are at increased risk of developing AD. The volumes were associated with different exercise-related assessments of PA.

Arnold Moya Evia Jr¹, David A Bennett^2,3, Julie A Schneider^2,3, Aikaterini Kotrotsou¹, Robert J Dawe², and Konstantinos Arfanakis^1,2
1Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Chicago, Illinois, United States, ³Rush University Medical Center, Chicago, Illinois, United States

Iron accumulation in the brain has been associated with aging, and Alzheimer’s disease (AD). MRI techniques that allow detection of iron accumulation may lead to development of biomarkers of AD pathology. Quantitative susceptibility mapping (QSM) was introduced recently, and is shown to be sensitive to changes in iron levels. Therefore, the purpose of this study was to investigate the neuropathologic correlates of magnetic susceptibility in subcortical gray matter, by conducting the first ex-vivo QSM-pathology investigation in a community cohort.

Yung-Chieh Chen¹, Cheng-Yu Chen^2,3, Shih-Wei Chiang^4,5, Hsiao-Wen Chung⁵, Yu-Te Wu¹, Ping-Huei Tsai², Yi-Hsiu Hsiao², Ming-Chung Chou⁶, Hung-Wen Kao⁴, and Chao-Ying Wang^4
1Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ²Department of Medical Imaging and Imaging Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ³Graduate Institue of Clinical Medicine, Taipei Medical University, Taipei, Taiwan, ⁴Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan, ⁵Graduate Institute of Biomedical Electrics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ⁶Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan

Idiopathic normal pressure hydrocephalus (NPH) is manifested clinically with classic triad of gait disturbance, incontinence and dementia. Quantification of anisotropy in terms of metrics such as the fractional anisotropy (FA) offers insight into microstructure alternations. The purpose of this study is to examine the diffusion tensor parametric behavior of anterior thalamic nucleus in response to memory changes in normal pressure hydrocephalus. Our study indicated that alternations of diffusion tensor metrics can be measured in thalamic nucleus responsible for memory in NPH patient, which may have potential clinical implications for responses monitoring at microstructure level in NPH patients under treatment.

Mario Torso¹, Laura Serra¹, Giovanni Giulietti¹, Roberta Perri², Lucia Fadda^2,3, Barbara Spanò¹, Camillo Marra⁴, Mara Cercignani^1,5, Carlo Caltagirone^2,3, and Marco Bozzali^1
1Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy, ²Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, IRCCS, Rome, Italy,³Department of Neuroscience, University of Rome "Tor Vergata", Rome, Italy, ⁴Institute of Neurology, Università Cattolica, Rome, Italy, ⁵Clinical Imaging Sciences Centre, Brighton & Sussex Medical School, Brighton, United Kingdom

This study, using Voxel-based lesion–symptom mapping (VSLM) and Voxel Based Morphometry analysis (VBM), investigated the contribution of White Matter lesions and regional grey matter atrophy in determining behavioural symptoms in patients with amnestic mild cognitive impairment (a-MCI), which is widely regarded as a prodromal stage of Alzheimer disease. Behavioural symptoms were quantified by Neuropsychiatric Inventory-12 (NPI-12). The main finding of the study was that a selective and bilateral lesion damage to the anterior thalamic radiation (ATR) was strictly associated to the presence and severity of patients’ apathy, in the absence of any contribution from regional grey matter loss.

Gunther Helms¹, Markus Matros², Kai Kallenberg³, Niels K Focke⁴, Inga Zerr⁵, Walter J Schulz-Schaeffer⁶, and Peter Dechent^1
1Cognitive Neurology, Göttingen University Medical Center, Göttingen, Germany, ²Imaging Diagnostics and Interventional Radiology, Klinikum Wolfsburg, Wolfsburg, Germany,³Neuroradiology, Göttingen University Medical Center, Göttingen, Germany, ⁴Neurology, Tübingen University Hospital, Tübingen, Germany, ⁵Neurology, Göttingen University Medical Center, Göttingen, Germany, ⁶Neuropathology, Göttingen University Medical Center, Göttingen, Germany

Reduced diffusivity is the radiological hallmark of spongiform degeneration of the basal ganglia in sporadic Creutzfeldt-Jacob disease (sCJD) which is difficult to detect by structural T1-weighted MRI. Using a novel semi-quantitative parameter for magnetization transfer (MT) with a high intrinsic contrast within GM, the MT-saturation, a significant reduction of MT was found in 5 sCJD patients compared to controls in caudate and putamen. This was correlated to the reduction in mean diffusivity thus associating hindered diffusion to increased water content. This can be explained by the influence of microcysts on diffusion and MT.

Babak A Ardekani¹, Alvin H Bachman¹, and Sang Han Lee^1
1The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States

We studied the rate of change of the area and circularity (CIR) of the corpus callosum in normal aging and early AD using 75 normal controls (NC), 51 mild cognitively impaired (MCI), and 21 mild AD (AD) subjects, scanned about two years apart. Programs automatically segmented and measured the CC. The CIR declined significantly with time in all three groups. Furthermore, the rates of decline were significantly different between groups. Change in the circularity of the corpus callosum may be a useful imaging biomarker of AD progression.

Hao Shu^1,2, Yongmei Shi¹, Gang Chen², Zan Wang¹, Duan Liu¹, Chunxian Yue¹, B. Douglas Ward², Wenjun Li², Zhan Xu², Guangyu Chen², Qihao Guo³, Jun Xu⁴, Shi-Jiang Li², and Zhijun Zhang^1
1Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China, ²Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ³Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China, ⁴Department of Neurology, Afï¬�liated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

APOE ε4 allele is the genetic risk factor and ε2 allele is the protective factor of Alzheimer’s disease (AD). However, the similar influences of the two alleles on the brain function have challenged the conceptual framework that the altered brain functions are directly linked to AD development. Given aging is another risk factor of AD, we utilized the resting-state functional connectivity approach to demonstrate that the opposite aging trajectories may contribute to the different AD risks between the two alleles, indicating the antagonistic pleiotropic property of APOE polymorphism and the necessity for including aging in AD related imaging genetics study.

C. M. Barth¹, D. A. Bennett², and K. Arfanakis^1
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States

Brain white matter hyperintense lesions (WMHs) are common in older adults. When diffusion imaging is used to investigate brain microstructure in cross-sectional voxel-wise studies of aging, it is necessary to control for the effects of WMHs on the diffusion parameters. This is often accomplished by including in statistical models a measure of the total volume of WMHs, which is problematic. The purpose of this study was to test the hypothesis that controlling for the presence of WMHs (binary mask), allows more sensitive detection of other microstructural abnormalities compared to controlling for the total volume of WMHs.

Keith S Cover¹, Ronald A van Schijndel¹, Adriaan Versteeg¹, Alberto Redolfi², Jérôme Revillard³, Baptiste Grenier³, David Manset³, Hugo Vrenken¹, Bob W van Dijk¹, Giovanni B Frisoni², and Frederik Barkhof^1
1VU University Medical Center, Amsterdam, Netherlands, ²IRCCS San Giovanni di Dio Fatebenefratelli, Italy, ³gnúbila France, France

To compare the reproducibility of the hippocampal atrophy rates over one year generated by different versions of the FreeSurfer/ReconAll and FSL/FIRST software packages using a back-to-back (BTB) reproducibility test. The test is based on the first Alzheimer's Disease Neuroimaging Initiative (ADNI1) data set - which includes two MPRAGE scans for each patient visit. The FSL/FIRST and FreeSurfer/ReconAll reproducibilities of hippocampal atrophy rates were similar. The poor reproducibility of the well documented bug in longitudinal mode of FreeSurfer 5.0.0 is clearly evident. The ADNI1-based BTB benchmark presented is a valuable way to compare performance of volumetric algorithms.

Christopher Nishioka¹, Christina Poh², and Shu-Wei Sun^2
1University of California, Riverside, CA, United States, ²Loma Linda University, CA, United States

Optic nerves of Alzheimer’s Disease (AD) patients were analyzed with diffusion tensor imaging (DTI) and compared to control patients. DTI scans were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Signs of white matter damage, including decreased fractional anisotropy, increased radial diffusivity and trace diffusion were seen in the AD patient population. These changes may be indicative of fiber loss and/or demyelination in the optic nerve.

Maria Marcella Laganà¹, Niels Bergsland^1,2, Mario Clerici^1,3, Pietro Cecconi¹, Giuseppe Baselli², Raffaello Nemni^1,3, and Francesca Baglio^1
1Fondazione Don Carlo Gnocchi ONLUS, Milan, Milan, Italy, ²Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Milan, Italy, ³Physiopatholgy Department, Università degli Studi di Milano, Milan, Italy

Recent MRI studies investigated the relationship between gray (GM) and white matter (WM) alterations in Alzheimer’s Disease, selecting areas known to be altered in AD and correlating their volumetric and DTI indices. We performed TBSS of 22 AD patients vs 23 healthy controls, mapped the results to the JHU-WM atlas, computed mean FA values of significant voxel corresponding to each atlas region and correlated them to GM volume, using VBM of the whole brain. A significant correlation between WM integrity and volume of near GM regions were obtained. The cause/effect interpretation of these results requires longitudinal multimodal MRI studies.

Amir Fazlollahi^1,2, Fabrice Meriaudeau², Luca Giancardo³, Christopher C. Rowe⁴, Victor L. Villemagne⁴, Paul Yates⁴, Olivier Salvado¹, Pierrick Bourgeat¹, and on behalf of the AIBL Research Group^5
1CSIRO Preventative Health Flagship, CSIRO Computational Informatics, Brisbane, QLD, Australia, ²Le2i, University of Burgundy, Le Creusot, France, ³RLE, Massachusetts Institute of Technology, MA, United States, ⁴Department of Nuclear Medicine and Centre for PET, Austin Hospital, Melbourne, VIC, Australia, ⁵http://www.aibl.csiro.au/, Australia

Since the incidence of cerebral microbleeds (CMBs) have come to attention as a potential biomarker of cerebrovascular disease and dementia, a computer-aided detection scheme to improve screening is required. In this work, a novel approach of CMB detection in SWIs is presented and compared to visual rating. The proposed method (1) identifies potential CMB candidates with their corresponding bounding boxes using a multi-scale Gaussian technique, (2) extracts a set of robust 3D Radon- and Hessian-based shape descriptors within the bounding boxes, as well as 2D Radon features computed on intensity-projection images, and (3) incorporates a cascade of random forests classifiers to reduce false detection rates.

Shu-Wei Sun¹, Chen-Fang Chung², Christopher Nishioka³, Hsiao-Fang Liang², and Wei-Xing Shi^2
1Loma Linda University, Loma Linda, CA, United States, ²Loma Linda University, CA, United States, ³University of California, Riverside, CA, United States

Synaptic deficits and brain atrophy are two major hallmarks in Alzheimer’s disease. Synaptic deficits usually occur early in contrast to the neuronal loss which usually occurs late. Thus, it is speculated that the early synaptic deficits may facilitate the later neuronal loss. A-beta was injected in the lateral geniculate nucleus, which affected the synapses but not the soma of RGCs. A-beta injected in axonal terminals may impair synapses to adversely affect the neural signal conduction. However, the injured synapses may not lead to a retrograded axonal degeneration to cause a neuronal loss.

Chieh-En Jane Tseng¹, Yu-Chun Lo¹, Yu-Jen Chen¹, Yun-Chin Hsu¹, Shur-Fen Susan Gau², and Wen-Yih Isaac Tseng^1
1Center of Optoelectronic Biomedicine, National Taiwan University, Taipei, Taiwan, ²Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

Abnormalities in functional connectivity have been reported within the default mode network (DMN) in autism spectrum disorder (ASD). This study uses diffusion spectrum imaging tractography to evaluate the white matter integrity of the white matter fiber tracts connecting the brain regions of the DMN in ASD. Differences between ASD and typically developing controls are subtle but show heterogeneity in structural connectivity.

Do-Wan Lee¹, Jung-Whan Min², Jung-Hoon Lee^1,3, Sang-Young Kim¹, Jin-Young Jung¹, Kyu-Ho Song¹, and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea, College of Medicine, Seoul, Seoul, Korea,²Department of Radiological Science, The Shingu University College of Korea, Seongnam, Seongnam, Korea, ³Department of Radiology, Kyunghee Medical Center, Seoul, Korea

The aim of presesnt study was to assess the effects of short-term binge ethanol intoxication on cerebral metabolite changes among the controls (CNTL), the low-dose-ethanol (LDE)-exposed, and the high-dose-ethanol (HDE)-exposed rats, which were determined with the ex vivo spectra. Our results showed that the normalized tNAA, GABA, and GSH levels were significantly altered among CNTL, LDE- and HDE-exposed rats. Moreover, the 6 pairs of normalized metabolite levels were significantly correlated in the individual rat data. Our ex vivo 1H HR-MAS NMRS results suggested some novel metabolic markers for the dose-dependent influence of short-term binge ethanol intoxication in the frontal cortex.

Yoshiyuki Hirano^1,2, Takayuki Obata^1,2, Chihiro Sutoh^1,2, Daisuke Matsuzawa^1,2, Naoki Yoshinaga^1,2, Zhongming Liu³, Hiroshi Ito², Hiroshi Tsuji², and Eiji Shimizu^1
1Research Center for Child Mental Development, Chiba University, Chiba, Chiba, Japan, ²National Institute of Radiological Sciences, Chiba, Chiba, Japan, ³School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, United States

We set out to investigate rsfMRI and DTI to assess the effect of cognitive behavioral therapy (CBT) on neural networks in patients with selective serotonin reuptake inhibitor (SSRI)-resistant social anxiety disorders (SAD). Increased neuronal connectivity at rest was found between the dorsal anterior cingulate cortex and striatum after 16-week CBT compared with healthy subjects. Also, decreased FA value was observed in the right anterior limb of the internal capsule after CBT. These results suggested that changes in emotional-related neural circuit by CBT exposed alterations in functional and structural MRI.

Beatriz Dionisio^1,2, Gracián García Martí^1,3, Conrado J Calvo⁴, Nicolás Peñaranda², Ana Beatriz Solana⁵, J. A. Hernández-Tamamés⁵, Luis Martí-Bonmatí³, and Julio Sanjuán^1,2
1University of Valencia, CIBERSAM, Valencia, Valencia, Spain, ²Instituto de Investigación Sanitaria, INCLIVA, Valencia, Valencia, Spain, ³Servicio de Radiología, Hospital Quirón de Valencia, Valencia, Spain, ⁴Instituto ITACA-Bio. Universitat Politècnica de València, Grupo Electrofiosiología y Bioingenería (GEB), Valencia, Spain, ⁵Fundación CIEN, Fundación Reina Sofía, Madrid, Spain

The pathophysiology of Auditory Hallucinations in Schizophrenia remains poorly understood due to the complexity to capture the spontaneous episodes and lack of knowledge about its neuronal dynamics. By using simultaneous EEG/fMRI techniques, we aimed to identify power spectral differences of brain waves, linking regional findings to intrinsic hemodynamic activations leading to AHs in chronic patients. Our results suggest that simultaneous EEG/fMRI seems to be a promising technique for thorough investigation on AHs neural spatiotemporal mechanisms alleviating technical limitations. Both modalities were correlated during the spontaneous AHs, with specific regional increase in theta EEG activity and hemodynamic activations in auditory and language cortical areas.

Maria Concepcion Garcia Otaduy¹, Marcus Vinicius Zanetti², Rafael T. Sousa², Wagner Farid Gattaz², Claudia da Costa Leite¹, and Rodrigo Machado-Vieira^2,3
1Laboratory of Magnetic Resonance in Neuroradiology, LIM 44, Institute and Department of Radiology, University of São Paulo, São Paulo, SP, Brazil, ²Laboratory of Neuroscience, LIM 27, Institute and Department of Psychiatry, University of São Paulo, São Paulo, SP, Brazil, ³ETPB, Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

In this study we assessed by in vivo 7Li-MRS lithium brain concentration in a group of patients with bipolar disorder after 6 weeks of lithium therapy, in order to test the hypothesis that patients presenting remission of the disease have a different absorption of lithium in the brain than non-remitted patients. Our results showed a higher brain to serum lithium ratio in the group of remitted patients when compared to patients with no remission. For remitted patients lithium brain concentration increased with lithium serum concentration, while in the non-remitted group there was no correlation between these measures.

Guoying Wang¹, Traute Demirakca¹, Markus Sack¹, Sabine Vollstaedt-Klein², Derik Hermann², Matthias Ruf¹, Karl Mann², and Gabriele Ende^1
1Department of NeuroImaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, ²Department of Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Brain activation in ACC to alcohol-related cues is able to elicit craving and relapse. In this ongoing study we used graph theory to test modular organization and topological properties of the ACC in abstinent alcohol dependent patients’ response to alcohol-associated cues. Repeated ANOVA analysis shows a trend towards decreased modularity in patients over early abstinence in which modular size as well as modular composition changed. This trend for less modularity implies an increasingly disrupted modular organization over early abstinence. Moreover, the ACC seems to be a hub in whole brain network with abnormal activity/importance in patients.

Benjamin W Krause¹, S Andrea Wijtenburg¹, Frank Gaston¹, Sarah Nisonger¹, Stephanie Korenic¹, and Laura Rowland^1,2
1MPRC, University of Maryland School of Medicine, Baltimore, MD, United States, ²Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

This study combined proton magnetic resonance spectroscopy, arterial spin labeling, and resting state fMRI to investigate anterior cingulate neurochemistry, regional cerebral blood flow, and functional connectivity in participants with schizophrenia and healthy controls. Patients had significantly lower tNAA levels than controls. Additionally, tNAA was positively correlated with cerebral blood flow, and this relationship was found to be weaker in patients than controls. We also found altered anterior cingulate functional connectivity in patients, however, tNAA was not significantly correlated with AC functional connectivity in patients or controls.

Kay Jann¹, Devora Beck-Pancer², Emily Kilroy³, Mirella Dapretto⁴, and Danny JJ Wang^1
1Department of Neurology, University of California, Los Angeles, Los Angeles, California, United States, ²) Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, United States, ³Division of Occupational Science, University of Southern California, Los Angeles, California, United States,⁴Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, United States

The aim of the present study was to characterize abnormal patterns of resting state network perfusion and functional connectivity using pseudo-continuous ASL (pCASL) perfusion MRI. PCASL-based resting state networks and their baseline perfusion were identified using ICA in 12 children with autism spectrum disorder (ASD). Our results show that altered perfusion in the DMN is related to autism symptom severity. Further, reduced DMN perfusion is associated with altered connectivity of anterior and posterior DMN, suggesting an association between baseline activity within networks, their connectivity and potentially alterations in stimulus processing and/or development of clinical symptoms in ASD.

Yu-Jen Chen¹, Chun-Chieh Fan², Yung-Chin Hsu¹, Yu-Chun Lo¹, Chih-Ming Liu³, and Wen-Yih Isaac Tseng^1
1Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taipei, Taiwan, ²Department of Cognitive Science, UC San Diego, CA, United States, ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taipei, Taiwan

In this study, we employed a high throughput tract-specific analysis, called tract-based automatic analysis, and a feasible statistical testing by performing threshold-free cluster enhancement (TFCE) and controlling family-wise error rate (FWER) to investigate the abnormalities of white matter tracts in schizophrenia using diffusion spectrum imaging. Our results showed consistent findings in association fibers and callosal fibers with previous studies. Furthermore, we also found many significant differences in projection fibers, such as frontal-striatal tracts and thalamo-cortical tracts. Moreover, clusters with significant difference could be discovered after applying TFCE and controlling FWER.

Sang-Young Kim¹, Do-Wan Lee¹, Hyunju Kim², Eunjung Bang², and Bo-Young Choe^1
1Department of Biomedical Engineering, The Catholic University of Korea, Seoul, Seoul, Korea, ²Korea Basic Science Institute, Seoul, Korea

In this study, we investigated the effects of chronic repetitive transcranial magnetic stimulation on GABA level in chronic unpredictable mild stress model using 1H-NMR spectroscopy. The prefrontal cortex and hippocampus tissues were harvested from rats brain and the spectra obtained from CPMG sequence were analyzed by LCModel. There were significant differences in GABA concentrations in chronic rTMS-treated rats compared to controls. Our finding indicates that chronic rTMS has a modulatory effect on GABAergic systems, suggesting its beneficial effects.

Brianne Mohl¹, Dhruman D. Goradia¹, Dalal Khatib¹, Usha Rajan¹, Arthur L. Robin¹, David R. Rosenberg¹, Noa Ofen^1,2, Joseph E. Casey³, Vaibhav A. Diwadkar¹, and Jeffrey A. Stanley^1
1Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan, United States, ²Merrill Palmer Skillman Institute, Wayne State University, Detroit, Michigan, United States, ³Psychology, University of Windsor, Windsor, Ontario, Canada

ADHD commonly occurs with a reading disability (RD); inattention has been linked with poorer reading measures in ADHD. However, the neural basis of the association has yet to be investigated. Age interactions and main effects of diagnosis were modeled for functional activations in ADHD+RD, ADHD-RD, and controls during a sustained attention fMRI task. Results suggest that developmental patterns may be similar in ADHD subgroups compared to controls, but the degree of hypoactivation in attention-related areas is significantly worse in ADHD+RD.

Su Lu¹, Lihua Qiu², John A. Sweeney³, and Qiyong Gong^2
1West China Hospital, Chengdu, Sichuan, China, ²West China Hospital, Sichuan, China, ³University of Texas Southwestern, TX, United States

Most previous structural studies of major depressive disorder (MDD) investigated volumetric changes in chronic medicated patients. In the present study, we investigate both the cortical thickness and surface area changes in first-episode, treatment-naïve, mid-life MDD. By studying 46 first-episode, treatment-naïve, mid-life adult MDD patients and 46 matched controls, we firstly observed greater rather than reduced cortical thickness at early stage of MDD. These changes in first-episode, treatment-naïve, mid-life MDD patients may reflect an active illness-related cortical change close to illness onset, and thus may provide important new insight into the early neurobiological manifestations of the disorder.

Ming-Chung Chou¹, Ming-Ting Wu^2,3, Hsiu-Lin Chen⁴, Yu-Chen Wu¹, and Pinchen Yang^5
1Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan, ²Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ³School of Medicine, National Yang Ming University, Taipei, Taiwan, ⁴Department of Pediatrics & Department of Respiratory Therapy, Kaohsiung Medical University & Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ⁵Department of Psychiatry, Kaohsiung Medical University & Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

In humans, birth weight generally correlates to gestational age and is easy to determine. Preterm infants are vulnerable to brain injuries, and brain injury due to prematurity and impaired brain development are inextricably intertwined. Nevertheless, there are few long-term brain MRI reports of adolescence born VLBW without overt neurological or mental disability. This study performed emotional-behavioral assessments and voxel-based DTI analysis in adolescents born VLBW without overt physical or mental disability. The results showed significant differences in DTI indices and emotional-behavioral outcomes between VLBW adolescents and control subjects. Therefore, we concluded that subtle WM alterations were significantly associated with emotional-behavioral measures in VLBW adolescents without overt disability.

Alessandra Griffa^1,2, Philipp S. Baumman^3,4, Carina Ferrari^3,4, Philippe Conus^3,4, Kim Q. Do^3,4, Jean-Philippe Thiran^1,2, and Patric Hagmann^1,2
1Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland, ³Service of General Psychiatry and Center for Psychiatric Neuroscience, Lausanne University Hospital, Lausanne, Switzerland, ⁴Naional Center of Competence in Research (NCCR) “SYNAPSY - The Synaptic Bases of Mental Diseases”, Switzerland

Schizophrenia is a complex psychiatric disorder involving impaired brain connectivity. The connectome framework allows describing various aspects of the brain topology in terms of network measures, and is therefore well suited for the investigation of schizophrenia. The purpose of the present study is to build on findings related to the alteration of global brain network properties, in order to identify the brain regions that mainly contribute to the integration and segregation deficit. Adopting a data-driven approach, we identified a distributed subnetwork affected in schizophrenia, and quantitatively characterized the related brain network topology reorganization.

Yuguang Meng¹, Xiaoping Hu², Jocelyne Bachevalier³, and Xiaodong Zhang^1
1Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Biomedical Engineering, Emory University, Atlanta, GA, United States, ³Yerkes National Primate Research Center and Department of Psychology, Emory University, Atlanta, GA, United States

Previous studies showed that visual working memory dependent on dorsolateral prefrontal cortex (dlPFC) was impaired in adult rhesus macaques after neonatal hippocampal lesions. To further explore the neuronal substrates for the deficient working memory performances, the integrity of the whole functional network of dlPFC was examined by resting-state fMRI and correlations were found between the functional connectivity in the dlPFC network and the working memory performances.

Ravi Prakash Reddy Nanga¹, Simon Vandekar², Sheila Shanmugan^2,3, Sarah Conlin^2,3, Kejia Cai¹, Mark A Elliott¹, Hari Hariharan¹, Jeanette Bradley^2,3, Ravinder Reddy¹, and Neill C Epperson^2,3
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ³Penn Center for Women’s Behavioral Wellness, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Menopausal women frequently report new onset decline in memory, focus, and organization- domains of cognition referred to as executive functions (EFs). Loss of estradiol effects on dopaminergic systems in the prefrontal cortex is thought to contribute to this phenomenon. We sought to test whether the psychostimulant lisdexamphetamine (LDX) improves EF in menopausal women and whether drug-induced changes in prefrontal glutamate and neural activation (measured at 7T) are responsible for improved working memory. This is the first study of its kind and may provide evidence to support LDX treatment in women with EF complaints related to natural or surgical/chemotherapy-induced menopause.

Xinyu Hu¹, Shiguang Li¹, Lizhou Chen¹, Qi Liu¹, Yi Liao¹, Fei Li¹, Wanjie Tang², Bin Li², Yanchun Yang², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center(HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China

White matter (WM) is suggested to play an important role in pathology of obsessive-compulsive disorder (OCD). In this study, we investigated the anatomic brain structures alterations of WM in OCD patients using both volumetric morphometry and multivariate pattern analysis. Decreased WM volume was revealed in bilateral external capsule of OCD patients compared to healthy controls, while discriminative regions were mainly involving the left middle frontal WM and bilateral temporo-patieto-occipital junction. Current study supported the potential translational role of WM for individual level diagnosis in OCD.

Dhruman D Goradia¹, Charles Frank¹, Andrew Lorence¹, Brianne Mohl¹, Dalal Khatib¹, Usha Rajan¹, Arthur Robin¹, David R Rosenberg¹, and Jeffrey A Stanley^1
1Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, United States

The prevalence of attention-deficit/hyperactivity disorder (ADHD) with a comorbid reading disability (RD) has been estimated to be as high as 45%. ADHD children with RD tend to have greater severity in cognition; however, morphological measures differentiating ADHD with RD from ADHD without RD remains poorly understood. The aim of this study is to investigate differences between subgroups in cortical thickness of key implicated areas in ADHD. As expected, ADHD with RD show a greater extent of cortex thinning than ADHD without RD in the prefrontal, parietal and cingulate areas, when compared to healthy individuals.

Huawei Zhang¹, Zhiyun Jia¹, Sugai Liang², Li Yin², Yi Huang², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), West China Hospital, Sichuan University, Chengdu, Sichuan, China, ²Department of Psychiatry, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Previous researches of suicide in depression always focused on either suicidal behavior or ideation. Present study aimed to give a more complete profile for the white matter microstructural abnormalities in depressive patients concerning suicide behavior. We found significant decrease in FA in the splenium corpus callosum in depressive patients comparing with healthy controls via MRI scans for diffusion tensor imaging and suicide attempters showed more significant decrease than patients without suicide attempt. Our results suggest that depression and suicide are associated with microstructure abnormalities of the white matter and people with suicide history have more severe cerebral alteration.

Hsiang-Yun Chien¹, Yung-Chin Hsu¹, Yu-Jen Chen¹, Yu-Chun Lo¹, Yao-Chia Shih¹, Susan Shur Fen Gau², and Wen-Yih Isaac Tseng^1
1Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ²Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taiwan, Taiwan

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder featuring the deficits of social communication and interactions. Past studies have reported that mirror neuron system (MNS), which is important for human social development by imitation, shows functional deficient in the social imitation tasks. In current study, we hypothesize the structural connectivity in MNS would also be abnormal in ASD patients. By analyzing the cortical thickness and fiber tracks of specific MNS regions, we found that the bilateral pars opercularis has thinner cortical thickness and the commissural fiber between them also shows abnormal in ASD group. The preliminary result implies the structural deficits of MNS in ASD patients.

Bochao Cheng¹, Lin Yuan², Xuhong Liao³, Su Lui¹, Xiaoqi Huang¹, Yong He², and Qiyong Gong^1
1HMRRC.Radiology Department, West China hospital of Sichuan University, Chengdu, Sichuan, China, ²State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China, ³Center for Cognition and Brain Disorders, Hangzhou Normal University, Zhejiang, China

We chose the left subgenual ACC as the seed region and explored the differed dynamic functional connectivity (D-FC) patterns in refractory and nonrefractory MDD in resting-state fMRI with the VPR combined with Kalman filtering approach. The results suggested that D-FC method can reveal the dysfunction brain network which is widely verified by the traditional static FC of MDD. And the cortical-limbic circuit, especially the prefrontal/temporal¨Climbic circuit, is the most stable varying important dysfunction brain network in MDD. The frontal part of left OFC, which shows reversed activity in MDD subtypes, may provide new insight into evaluate the treatment.

Ju Liu¹, Jianliang Yao¹, Siyou Qiu¹, Yi Zhang¹, and Yijun Liu^2
1School of Life Science and Technology, Xidian University, Xi'an, Shanxi, China, ²Department of Biomedical Engineering, Peking University, Beijing 100871, China

Prader-Willi syndrome(PWS) is a genetic imprinting disorder associated with hyperphagia and early childhood obesity.To study the neurobiological drive for overeating implicated in Prader-Willi syndrome,the current study combined the resting-state fMRI and Granger causality analysis (GCA) techniques to investigate the interactive causal influences among key neural pathways underlying overeating in PWS.Our data revealed significantly enhanced causal influences from theamygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala. This study provides both a new methodological and neurobiological perspective to aid in a better understanding of neural mechanisms underlying common dietary obesity in the general public.

Chenwang Jin¹, Kai Yuan², Tao Dong², Ce Chen³, Hongmei Wang¹, Wei Wang³, Ming Zhang¹, Wei Qin², and Jie Tian^2
1Departmentof Medical Imaging,The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shanxi, China, ²School of Life Science and Technology, Xidian University, Xi'an, Shanxi, China, ³Department of psychiatry,The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shanxi, China

Internet addiction (IA) has become a serious society problem due to the bad influence on the adolescents. Adolescence is an developmental stage, encompassed by alterations in physical, psychological, and social development, and those behavior characteristics of IA may introduce injuries to teenage development in the future. Thus, it is critical to understand the neurobiological mechanisms underlying this disorder. Although white matter integrity abnormalities have been reported in IA adolescents, little is known about the brain structural topological property changes and the relationship with the IA severity.

Natalia Semenova^1,2, Dmitry Kupriyanov³, Maxim Ublinskiy¹, Irina Lebedeva⁴, and Tolibjon Akhadov^1
1Children Emergency Surgery and Trauma Institute, Moscow, Russian Federation, ²N.M.Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russian Federation, ³Philips Healthcare, Moscow, Russian Federation, ⁴Mental Health Research Center of Russian Academy of Medical Sciences, Moscow, Russian Federation

The aim of this study was the analysis of motor cortex metabolism dynamics during period of BOLD response to fMRI motion task. The BOLD signal demonstrated maximum at the 6th sec after target stimulus for both patient and control groups, with lower intensity for schizophrenia patients. For control group, NAA decreased at the 12th second after fMRI motion task presentation and recovered to the initial value at the 15th second. Patient group demonstrates different dynamics of NAA in motor cortex – with smaller NAA intensity changes.

Ying Liu¹, Huishu Yuan¹, Xiangzhu Zeng¹, Zheng Wang¹, and Han Zhang^2
1Radiology, Peking University Third Hospital, Beijing, Beijing, China, ²The consultation liaison, Peking University Mental Health Institute, Beijing, Beijing, China

As important diagnostic tools for cerebral microstructure impairment, diffusion tensor imaging (DTI) and diffusion kurtosis imaging(DKI) have the ability to assess the white matter characteristics by investigating water diffusion with a Gaussian and a non Gaussian models. Fractional anisotropy is a very important parameter of DTI. Diffusion kurtosis imaging is an extension of diffusion tensor imaging. Fractional anisotropy of kurtosis (FAk) is similar to FA in DTI, and can be conveniently defined as FAk. The aim of this study is to evaluate the differences between depression and comorbid hypertension in depression using FA of DTI and FAk of DKI.

Siân E. Robson¹, Emma L. Hall¹, Matthew J. Brookes¹, Lena Palaniyappan², Peter F. Liddle², Mary C. Stephenson¹, Molly Simmonite², Elizabeth B. Liddle², Michael Skelton², Nikolaos G. Christodoulou², Ayaz Qureshi³, and Peter G. Morris^1
1School of Physics and Astronomy, University of Nottingham, Nottingham, Notts, United Kingdom, ²Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, Notts, United Kingdom, ³Nottinghamshire Healthcare NHS Trust, NHS, Nottingham, Notts, United Kingdom

Abnormalities in structure, function and neurotransmission are seen in patients with psychosis, particularly in nodes of the ‘salience network’: the anterior cingulate cortex (ACC) and insula. This study used 7T MRI and MRS to investigate tissue composition and metabolite concentrations in these regions and an occipital control region. Reductions in white matter were found in patients’ insula, along with decreases in glutamate concentration. Correction for tissue fraction removed the difference in glutamate, perhaps erroneously, since glutamate is mostly present in grey matter but differences in tissue fraction between patients and controls were seen in white matter only.

S. Andrea Wijtenburg¹, Benjamin W Krause¹, Frank Gaston¹, Stephanie Korenic¹, Sarah Nisonger¹, Peter Kochunov¹, Danny JJ Wang², L Elliot Hong¹, and Laura M Rowland^1,3
1MPRC, University of Maryland School of Medicine, Baltimore, MD, United States, ²Neurology, University of California Los Angeles, CA, United States, ³Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Older adults with schizophrenia (SZ) have significant memory impairments when compared to healthy age-matched controls, and the pathophysiology of these memory impairments is poorly understood. Assessments of declarative verbal memory, glutamate, and regional cerebral blood flow from brain regions associated with verbal memory function (hippocampus and anterior cingulate) were conducted in older adults. Data were acquired on a 3T scanner from stable, chronic younger and older adults with SZ and age-matched controls. Results showed lower glutamate, CBF, and verbal memory scores in older adults with SZ.

Lizhou Chen¹, Xinyu Hu¹, Qi Liu¹, Yi Liao¹, Ning He², Fei Li¹, Ying Chen², Lanting Guo², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center(HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, China

White matter (WM) abnormality had been studied with diffusion tensor imaging with inconsistent results while underline mechanism remained unclear. Present study performed in-depth investigation into WM abnormalities in a relatively large sample of ADHD children by using multiple diffusion parameters, including fractional anisotropy (FA), radial diffusivity and axial diffusivity. The relationship between FA and neuropsychiatric measurements was also explored. Increased FA with discrepant cellular alternating patterns was detected in left cingulate bundle and posterior-body of corpus callosum, and the alternation of FA correlated with some cognitive domains.

Xiaoyi Liu¹, Yunyao Lai¹, Xijin Wang², Chuanxi Hao¹, Lei Chen¹, Zhenyu Zhou¹, Xin Yu², and Nan Hong^1
1Peking University People's Hospital, Beijing, China, ²Institute of Mental Health, Peking University, Beijing, China

In this study, we examined the sub divisional morphology of cingulate cortex in antipsychotic-naïve schizophrenia by using a surface-based analysis. And we also investigated the changes of morphology in cingulate cortex and their associations with clinical variables and cognitive performance. The results show that changes of cingulate cortex play a critical role in schizophrenia, and demonstrated that the left PCC volume deficit may play a role in the working memory of the disorder. And these are not attributable to contamination by antipsychotic drugs.

zhan feng¹, manli huang², and hong yang^2
1radiology, The First Affiliated Hospital of College of Medicine, Zhejiang University, hangzhou, zhejiang, China, ²The First Affiliated Hospital of College of Medicine, Zhejiang University, zhejiang, China

The prefrontal¨Climbic network(PLN) is dysregulated in major depressive disorders(MDD),We use the Granger causality analysis to study variation of effective connectivity in PLN.The decrease of effective connectivity of prefrontal cortex proved that top-down cognitive control function reduction existed in MDD. The abnormality of effective connectivity from right insular cortex to rACC showed that there was something wrong with the SN switching function between central-executive network and default-mode networks under the resting state.These specific abnormal connectivities further supplemented the dynamic active process of PLN of MDD patients.

Yishin Chang¹, Julia P. Owen¹, Shivani Desai², Emily Fourie², Susanna Hill², Anne Arnett², Julia Harris², Elysa Marco², and Pratik Mukherjee^1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²Department of Neurology, University of California, San Francisco, California, United States

Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. However, there are children with sensory processing differences (SPD) who do not meet other criteria for ASD diagnosis. We use probabilistic diffusion fiber tractography to compare the white matter connectivity of children with ASD and SPD to neurotypical children. Both the ASD and SPD groups demonstrate abnormal connectivity in sensory processing pathways, while the ASD group alone demonstrates abnormal connectivity in tracts thought to subserve social and emotional processing. These observations help elucidate the roles of specific neural circuits in neurodevelopmental disorders.

Mu-Lan Jen¹, Che-Min Lin², Jasin Wong¹, Shwu-Hua Lee², Yau-Yau Wai^1,3, and Ho-Ling Liu^1,3
1Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ²Department of Psychiatry, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ³Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan

The purpose of this study was to evaluate the whole-brain cerebral blood flow (CBF) change in late-life depression (LLD) using voxelwise analysis. Twenty-one LLD patients and seventeen elder controls underwent background suppressed 3D pseudo-continuous arterial spin labeling (PCASL) MRI scans. This study showed that significant (P<0.01, corrected) hypoperfusion in LLD in prefrontal cortex included left rectal, subcallosal and medial frontal gyrus. Also, CBF tend to be lower in LLD in the bilateral anterior cingulate gyrus.

Tai-Ying Liu^1,2, Guan-Hua Huang¹, Cheng-Ta Li^3,4, Yong-Sheng Chen⁵, Tung-Ping Su^3,4, Jen-Chuen Hsieh^1,2, and Li-Fen Chen^1,2
1Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, ²Integrated Brain Research Unit, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ³Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, ⁴Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ⁵Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan

Treatment-resistant depression (TRD), with up to 20% of patients not responding to antidepressant treatment, is a crucial issue. Add-on repetitive transcranial magnetic stimulation (rTMS), an emerging treatment approach for TRD, has been reported to modulate regional brain activity of the prefronto-thalamo-limbic system in depressed patients. Whereas how brain structures can be modulated by rTMS in depression remains unclear. This study aimed to investigate, through voxel-based morphometric analysis, the effect of rTMS on gray matter density in TRD patients.

Hu Cheng¹, Sharlene Newman¹, Joaquin Goni Cortes¹, Jerillyn S. kent¹, Josselyn Howell¹, Amanda Bolbecker¹, Aina Puce¹, Brian F. O'Donnell¹, and william P. Hetrick^1
1Indiana University, Bloomington, IN, United States

Recent studies indicate less dynamic brain function in schizophrenia patients. Because head motion and other confounds can affect the FC and its variability, investigation of FC dynamics by directly comparing FC over time can be invalid. We propose a method to tackle this problem. By constructing two FCs from interleaved time points of the resting state time course, we can extract the variance of FC irrelevant to brain dynamics, and use it as a baseline in the evaluation of FC change. Using this approach, we found that the schizophrenia patients exhibited smaller variations of functional network compared to normal controls.

Kayako Matsuo¹, Chih-Min Liu^2,3, Shen-Hsing Annabel Chen⁴, Aleksandr Aleksandrovich Simak^5,6, Chen-Chung Liu², Tzung-Jeng Hwang^2,3, Ming-Hsien Hsieh², Yi Ling Chien², Hai-Gwo Hwu^2,7, and Wen-Yih Isaac Tseng^1,3
1Advanced Biomedical MRI Lab, National Taiwan University College of Medicine, Taipei, Taipei, Taiwan, ²Department of Psychiatry, National Taiwan University Hospital & College of Medicine, Taipei, Taiwan, ³Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan, ⁴Division of Psychology, School of Humanities and Social Sciences, Nanyang Technological University, Singapore, Singapore, ⁵Functional Neuroimaging Group, Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, ⁶Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan, ⁷Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

We investigated a new method to observe genotypic effects on brain activation using 104 people including patients with schizophrenia and controls with genotypes of NRG1-P3. After conventional SPM of fMRI with verbal working memory, group average contrast estimate volumes of 4 subject groups (schizophrenia/control by C-allele/TT-genotype) provided 4-value sets for the whole brain coordinates, and the 4-value sets underwent k-means clustering that yielded cluster means (10 divisions). These cluster means were then used as ‘true’ contrast definition values in SPM. We successfully obtained cluster-specific SPMs that helped observations of influences by age and task accuracy in a data-driven manner.

Qi Liu¹, Lizhou Chen¹, Xinyu Hu¹, Ying Chen¹, Fei Li¹, Yuanyuan Li¹, Ning He¹, Lanting Guo¹, Qiyong Gong¹, and Xiaoqi Huang^1
1West China Hospital of Sichuan University, Chengdu, Sichuan, China

Abnormal Gray matter volume (GMV) has been suggested to be an important neuroimaging biomarker of Attention Deficits/Hyperactivity Disorders (ADHD). Present study compared GMV of drug-naïve ADHD boys with well-matched controls using voxel-based morpphometry analysis, and explored the age effect as well as correlation with neuropsychological measurements. Decreased GMV was revealed in bilateral temporal lobes extending to amygdala, which showed positive correlation with some cognitive functions. Moreover, no significant correlation was found between GMV with age in ADHD boys, as seen in healthy controls, which might indicate an abnormal developmental trajectory of GMV in ADHD.

Mark S. Brown¹, Sarah Steinmetz², Susan L. Hepburn³, Deb Singel⁴, and Donald C. Rojas^5
1Radiology, University of Colorado Denver, Aurora, CO, United States, ²University of Colorado Denver, Aurora, CO, United States, ³Psychiatry & Pediatrics, JFK Partners/University of Colorado School of Medicine, Aurora, CO, United States, ⁴Brain Imaging Center, University of Colorado Denver, Aurora, CO, United States,⁵Psychiatry, University of Colorado Denver, Aurora, CO, United States

Auditory Gamma band MEG responses and auditory GABA levels, measured with MRS J-editing techniques, were measured in 25 healthy controls and 24 individuals with autism spectrum disorder (ASD). The results show lower GABA and transient gamma band power in the ASD subjects compared to healthy controls. Transient gamma band power correlated with GABA levels in the control group and approached significance in the ASD group. The results are consistent with our previous preliminary work suggesting that auditory gamma band responses are related to auditory GABA.

Hong Yang¹, Zhan Feng¹, Shunliang Xu¹, and Manli Huang^2
1Department of Radiology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China, ²Department of psychiatry, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China

The resting state functional connectivity were examined between the two hemispheres in MDD patients using a recently proposed measurement named ¡®¡®voxel-mirrored homotopic connectivity¡¯ (VMHC)¡¯. Twenty-three first-episode, medication-naive patients were compared with twenty matched controls. Compared to the controls, the MDD patients showed significant decreased VMHC in: superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, hippocampus, parahippocampa gyrus, middle temporal gyrus, insula, putamen, caudate, parietal lobe, middle occipital gurus and precuneus. These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients. Furthermore these impaired long-range connections likely reflect failure functional networks integration process in MDD.

Min Guan¹, Minghao Dong², Xiangsheng Zhang³, Wei Qin², Meiyun Wang¹, Dapeng Shi¹, and Jie Tian^2
1Radiology, People's Hospital of Zhengzhou University, ZhengZhou, HeNan, China, ²School of Life Science and Technology of XiDian University, Shannxi, China, ³Urology, People's Hospital of Zhengzhou University, HeNan, China

Psychogenic ED has a high prevalance and a significant impact on the quality of life of sufferers and their partners.Little is known about the central pathological mechanism of psychogenic ED patients. Resting-state functional MR imaging and the Regional homogeneity (ReHo) method has been successfully used to investigate the functional modulations in patients with phychiatric diseases. We investigated neural activity in the resting state of psychogenic ED using ReHo method.Our present study for the first time demonstrated psychogenic ED exhibited decreased ReHo in the left VMPFC and right hippocampus, may leading to further improvement of the understanding of the pathogenetic mechanism.

Atilla Gonenc^1,2, Mary C Malloy³, David G Harper^1,3, and Brent Forester^1,3
1Harvard Medical School, Boston, MA, United States, ²McLean Imaging Center, Belmont, MA, United States, ³McLean Hospital, Belmont, MA, United States

Currently, there is lack of data in geriatric bipolar disorder overall and in geriatric bipolar depression in particular. In this study, we utilized a recently developed diffusion magnetic resonance imaging technique to assess its sensitivity in detecting microstructural changes in the brain of older adults with bipolar disorder.

Oscar Gustafsson^1,2, Maria Ljungberg^1,2, Arvid Carlsson³, Maria L Carlsson³, Eva Forssell-Aronsson^1,2, Tord Ivarsson⁴, Lars Jönsson⁵, Karin Melin⁴, and Göran Starck^1,2
1Division of Medical Physics and Medical Engineering, Sahlgrenska University Hospital, Göteborg, Sweden, ²Department of Radiation Physics, Göteborg University, Göteborg, Sweden, ³Institute of Neuroscience and Physiology, Göteborg University, Göteborg, Sweden, ⁴Department of Child & Adolescent Psychiatry, Göteborg University, Göteborg, Sweden, ⁵Department of Radiology, Sahlgrenska University Hospital, Göteborg, Sweden

A morphometric analysis of treatment-naïve adolescents newly diagnosed with obsessive-compulsive disorder (OCD), utilizing the image analysis software FreeSurfer, was performed. Cortical thickness and volume of subcortical structures was examined with a multivariate method (scaled subprofile modeling) which produces patterns of areas related to the disorder. Analysis of difference between patients compared to healthy controls and correlation to symptom severity, measured with the Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS), were performed. A significant correlation between cortical thickness and CYBOCS was found. Areas of major effect in the corresponding pattern included the left fusiform gyrus and the left parietal lobe.

Chang-Woo Ryu¹, Geon-Ho Jahng¹, Dal Mo Yang¹, Woo Suk Choi², and Eui Jong Kim^2
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, ²Radiology, Kyung Hee University Medical Center, Seoul, Korea

Bilateral tinnitus has different resting state connectivity from monolateral tinnitus.

Xiangzhu Zeng¹, Huishu Yuan¹, Ying Liu¹, Zheng Wang¹, and Han Zhang^2
1Dept of Radiology, Peking University Third Hospital, Beijing, Beijing, China, ²Dept of the consultation liaison, Peking University Mental Health Institute, Beijing, Beijing, China

As a new diagnostic tool for cerebral microstructure impairment, Diffusion Kurtosis imaging (DKI) has the ability to assess the white matter impairment of tissues by investigating water diffusion with a non-Gaussian model. Mean kurtosis(MK) is a key parameters of DKI and reveals the white matter damage accurately. This work evaluates the diagnostic utilities of MK in the case of depression and hypertension and specifies the white matter impairment in these patients.

Jochen Bauer¹, Anne Werner¹, Waldemar Kohl¹, Anya Pedersen², Harald Kugel³, and Patricia Ohrmann^1
1Department of Psychiatry, University Hospital Münster, Münster, Germany, Germany, ²Psychology, University of Münster, Münster, Germany, Germany, ³Institut for Clinical Radiology, University Hospital Münster, Münster, Germany, Germany

Investigation of the glutamatergic metabolism in patients with Attention Deficit Hyperactivity Disorder (ADHD) with magnetic resonance spectroscopy. Increased glutamate level in the anterior cingulate cortex in patients reveals a glutamatergic dysfunction.

Justin Alexander Long¹, Lora Talley Watts¹, Jonathan Chemello¹, Qiang Shen¹, Shiliang Huang¹, and Timothy Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

This study investigated the spatiotemporal dynamics of diffusion, T2 and fractional anisotropy associated with mild traumatic brain injury (TBI) following NBO treatment. Diffusion, T2 and fractional anisotropy changes generally indicated that lesion severity increased following administration of NBO treatment compared to the air treated control group. T2 increased in the NBO treatment groups initially (3 hrs and day 1 measures), returning to similar magnitude as the air treated control group by Day 2 and then showed a significant increase by 14 days post injury. ADC and FA differences were significant at all time points. Multi-parametric MRI offers a range of biomarkers that are sensitive to different tissue types at different stages of TBI and can distinguish differences in outcome based on treatments applied.

Maurizio Bergamino¹, Rashmi Singh¹, Timothy Meier¹, Rayus Kuplicki^1,2, Christopher Nerio³, David Polanski³, and Patrick SF Bellgowan^1,4
1Laureate Institute for Brain Research, Tulsa, OK, United States, ²Tandy Computer Science, The University of Tulsa, Tulsa, OK, United States, ³Department of Athletics, The University of Tulsa, Tulsa, OK, United States, ⁴Faculty of Community Medicine, The University of Tulsa, Tulsa, OK, United States

Investigation of white matter structural changes associated with sports-related concussion and the accumulation of head hits in young male athletes using DTI.

Bhanu Prakash KN¹, Sanjay K Verma¹, Yevgen Marchenko¹, Sankar Seramani¹, Kan Enci Mary², Charmaine Childs³, Lu Jia², Andrew A Maudsley⁴, and Sendhil Velan S^1,5
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Combat Protection and Performance Lab, Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Singapore, ³Centre for Health and Social Care Research, Faculty of Health and Wellbeing, Sheffield Hallam University, United Kingdom, ⁴Miller School of Medicine, University of Miami, Florida, United States, ⁵Clinical Imaging Research Centre, Singapore, Singapore

Measurement of in vivo temperature is of relevance in traumatic brain injuries including survival outcome of patients. Whole brain 3D MRSI approach with larger spatial coverage is highly desirable for assessing changes in cerebral metabolism and investigation of hot spots. 3D Echo-planar spectroscopic imaging (EPSI) on a pre-clinical scanner was implemented to evaluate the brain temperature changes in mild and severe traumatic brain injuries (TBI) in rodents. Brain temperature across the brain was investigated in mild and severe TBI rodents. Reduction in acquisition time along with high spatial resolution allows translation of this technology to a clinical setting, and for investigating changes in brain temperature due to TBI, stroke, cancer, epilepsy and whole brain metabolic imaging in animals and humans.

Brenda Bartnik-Olson¹, Katsunori Shijo^2,3, Sima Ghavim², Neil Harris², and Richard Sutton^2
1Loma Linda University, Loma Linda, CA, United States, ²University of California Los Angeles, Los Angeles, CA, United States, ³Nihon University School of Medicine, Tokyo, Japan

Traumatic brain injury initiates a cascade of events including increased oxidative stress that contributes to the period of generalized metabolic depression. Previously, sodium and ethyl pyruvate supplementation was shown to reduce cell death, attenuate reductions in cytochrome oxidase activity, and improve recovery following experimental TBI. In this study we used 13C NMR spectroscopy to determine if sodium or ethyl pyruvate supplementation influences the activity of metabolic pathways associated with the intracellular redox state and oxidative metabolism. Our findings show improvements in neuronal and astrocyte oxidative metabolism following sodium pyruvate supplementation and a reduction in the amount of glucose metabolized via the pentose phosphate pathway following both sodium and ethyl pyruvate use, suggesting an improved redox state. These findings may explain, in part, the mechanisms responsible for the beneficial effects of pyruvate supplementation following experimental TBI.

Marjorie Villien¹, Brian Edlow², Elissa McIntosh², Maulik P. Purohit³, Andre van der Kouwe¹, Janet C. Sherman², David Greer⁴, Ross Zafonte³, and Ona Wu^1
1Martinos Center for Biomedical Imaging, MGH/Harvard Medical School, Boston, MA, United States, ²Massachusetts General Hospital, Boston, MA, United States, ³Spaulding Rehabilitation Hospital, Boston, MA, United States, ⁴Yale School of Medicine, New Haven, CT, United States

Traumatic brain injury (TBI) is one of the leading causes of morbidity in the US, with the highest incidence among young adults. The majority of mild TBI patients recover within a few months, but for up to 20% symptoms persist and lead to a devastating impact on interpersonal relationships and potentially to long-term disability, named as persistent post-concussion syndrome (PPCS). The pathophysiological basis of PPCS remains unknown. This resting state fMRI study demonstrates that multiple resting brain networks are altered in young athletes with PPCS and also suggest that the inferior parietal lobule is implicated in the pathogenesis of PPCS.

Hardik Doshi¹, Jun Liu², Robin Hanks³, E Mark Haacke⁴, and Zhifeng Kou^4
1Biomedical Engineering, Wayne State University, Detroit, MI, United States, ²Department of Radiology, Second Xiangya Hosipital,Central South University, Hunan, China,³Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, United States, ⁴Biomedical Engineering and Radiology, Wayne State University School of Medicine, Detroit, MI, United States

TBI is one of the major epidemics around the world. It causes many deaths and disabilities every year. Blood from hemorrhages is an important biomarker. Susceptible Weighted Imaging (SWI) is most sensitive MRI sequence for detection of blood. Veins and arteries undergo lot of pressure and stress during the event of trauma. It can easily cause a vessel wall to break down. Depending on the type of blood vessel (Artery or Veins), recovery varies significantly. Location and severity of the insult also plays an important role. The main objective of this study is to investigate the spatial relationship between hemorrhagic bleed and different types of vessels, e.g. veins vs. arteries, as well as its relationship with TBI patients’ clinical and outcome information

Andrew Knutsen¹, Philip Bayly², Jerry Prince³, John Butman⁴, and Dzung Pham^1
1Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation, Bethesda, MD, United States, ²Washington University in St. Louis, MO, United States, ³Johns Hopkins University, MD, United States, ⁴Clinical Center, National Institutes of Health, MD, United States

Tagged MR images of brain deformation during mild angular acceleration were acquired in four live human subjects. High resolution MPRAGE and diffusion images were also acquired, and were registered into the tagged image space. Two-dimensional principal strains were computed from the tagged MR images and mapped into anatomical structures identified using the MPRAGE. Strains were also computed along principal fiber directions identified via DTI. Quantifying strain in the live human brain is important to understand the role that brain structure plays in the deformation response to skull acceleration, and to help validate computation models of traumatic brain injury.

David K Wright^1,2, Jack Trezise³, Leigh A Johnston^1,4, Roger Ordidge², Terence J O'Brien³, and Sandy R Shultz^3
1The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia, ²Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia, ³Department of Medicine, Royal Melbourne Hospital, Victoria, Australia, ⁴Neuroengineering Laboratory, Department of Electrical and Electronic Engineering, The University of Melbourne, Victoria, Australia

Although a single brain concussion rarely has lasting effects, recurrent concussions may result in cumulative chronic neurological and neuropsychiatric impairments. The current clinical management of concussion is based on assessing for the resolution of neurocognitive impairments, however an asymptomatic state may not accurately indicate that the brain has fully recovered. Here we investigate the potential of magnetic resonance imaging (MRI) as a platform in assessing the brain effects of concussion. The results show MRI to be sensitive to the subtle pathophysiological changes that occur in the concussed brain and contribute to the cumulative and degenerative effects of repeated concussion.

Sanjay K Verma¹, Bhanu Prakash KN¹, Sankar Seramani¹, Enci Mary Kan², Kian Chye Ng², Mui Hong Tan², Jia Lu², and S Sendhil Velan^1,3
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Combat Protection and Performance Lab, DSO National Laboratories, Singapore, Singapore, ³Clinical Imaging Research Centre, Agency for Science, Technology and Research, Singapore, Singapore, Singapore, Singapore

Traumatic brain injury due to blasts by improvised explosive devices is increasing, creating various neuropsychological dysfunctions such as attention deficit, working function, motor skills etc in both animals and humans. We investigated the effect of open field blast injuries on rat brain using Diffusion tensor imaging which provides the degree as well as directionality of water diffusion in brain. The increase in FA , AD and decrease in RD at day 1 in CC may be probably due to edema or change in the water content within the myelin sheath. Decrease of diffusivity in the cortex and hippocampus indicates cytotoxic edema and slight increase at day 28 probably due to reduced tissue cellularity.

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

Traumatic brain injury has been reported in professional combat athlete population. We have developed the protocol of Professional Fighters’ Brain Health, in which the professional fight athletes are participated and scanned using MRI for a baseline evaluation and annually over 4 years. The initial finding in the first year scan has shown that the number of knockout predicts the diffusion change in white matter. In this study, we presented the preliminary result of the functional connectivity alternation. The study indicated that the functional motor network connection is decreased according to the number of fights during 1 year.

Armin Iraji¹, Hamid Soltanian-Zadeh², Randall Benson¹, E. Mark Haacke¹, and Zhifeng Kou^3
1Wayne State University, DETROIT, MI, United States, ²University of Tehran, Tehran, Iran, ³Wayne State University, Detroit, Michigan, United States

Detection of the neuropathological or physiological substrates may hold the best opportunity to improve the diagnosis and proactive treatment of mTBI patients. Functional and structural connectivities can be a good index to investigate the effect of brain injury. The posterior cingulate cortex is renowned as the brain’s central hub, which integrates and relays the information; therefore, it involves many brain functional networks and regulates their activation based on information that it gathers from the entire central nervous system (CNS). We examine the change in the PCC connectivity using both resting state fMRI and probabilistic diffusion tractography.

Alexander Peter Lin¹, Molly Charney¹, Huijun Vicky Liao¹, Sai K Merugumala¹, Christine Baugh², and Robert A Stern^2
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Center for Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, MA, United States

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition that can result from sports-related repetitive brain trauma. It is characterized by the deposition of tau proteins which may induce neuroinflammation. The goal of this study is to measure neuroinflammation in retired NFL athletes at high risk for CTE by measuring glutathione levels using magnetic resonance spectroscopy. Our results show that glutathione levels are reduced in NFL players when compared to age-matched professional athlete controls with no history of head injury. As GSH is utilized by the brain to neutralize reactive oxidative species, the reduction is reflective of neuroinflammation.

Elizabeth Hutchinson^1,2, Michal Komlosh^1,2, Alan Barnett^1,2, Mustafa Irfanoglu^1,2, Evren Ozarslan^1,3, Susan Schwerin^2,4, Sharon Juliano^2,4, and Carlo Pierpaoli^1
1STBB, NICHD/NIH, Bethesda, MD, United States, ²Center for Neuroscience and Regenerative Medicine, USUHS, Bethesda, MD, United States, ³Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States, ⁴Anatomy, Physiology and Genetics, USUHS, Bethesda, MD, United States

We have applied the recently developed MAP-MRI framework to the investigation of brain injury. MAP-MRI provides an analytic representation of the diffusion propagator and a series of novel diffusion-MRI “stains” that quantify non-Gaussian water diffusion. The combination of this recent advance in diffusion modeling and the ability to quickly image fixed tissue at high spatial resolution has allowed us to identify new markers of microstructural change in the mouse cortex following controlled cortical impact and to characterize the spatio-temporal profiles of these abnormalities from 24 hours to 3 months following injury.

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

In order to investigate different pathological changes¡¯ influences on DTI parameters such as axial diffusivity, radial diffusivity, mean diffusivity and fractional anisotropy and to explain the contradictious clinical observations, a Monte Carlo simulation study was conducted. The preliminary results showed that, in acute stage, axonal injury and cytotoxic edema were the primary factors determining DTI parameter changes, and they could literally lead to opposite observations. In subacute stage, demyelination and vasogenic edema were the predominant factors, which affected DTI parameters in a similar way. Axial and radial diffusivity were sensitive to axonal injury and demyelination, but they were easily disrupted by edema., but they were easily disrupted by edema.

Sanjay K Verma¹, Sankar Seramani¹, Bhanu Prakash KN¹, Jadegoud Yaligar¹, Enci Mary Kan², Kian Chye Ng², Jia Lu², and S Sendhil Velan^1,3
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Combat Protection and Performance Lab, DSO National Laboratories, Singapore, Singapore, ³Clinical Imaging Research Centre, Singapore, Singapore

TBI is a serious and global public health issue. Fluid percussion injury in rats is a commonly used animal model simulating traumatic brain injuries. In this study, we investigated the metabolic changes by MRS, structural changes using DTI in hippocampus and changes in microvasculature by SWI in FPI based mild and severe TBI. Neuronal loss, membrane disruption is observed in mild and severe injuries by MRS. The structural changes and micro-vessel damage was observed by DTI and SWI respectively. The combined imaging and spectroscopic assessment provides valuable markers for investigating structure and metabolism in mild and severe injuries.

Elham Shahinfard¹, Michael Jarrett¹, Irene Vavasour¹, Shannon Kolind¹, Enedino Hernández-Torres¹, Jack Taunton¹, David K Li¹, and Alexander Rauscher^1
1University of British Columbia, Vancouver, BC, Canada

Repetitive concussion or hits to the head can have serious cumulative effects. Studies in animals and in humans with moderate to severe traumatic brain injury suggest damage to the axon's myelin sheath. We studied two ice hockey teams over one season and measured the brain's myelin water fraction before and after concussion. Voxel-wise tract based statistical analysis showed significant reduction of myelin water fraction at two weeks post-injury for the eleven concussed subjects. Using an atlas-based based region of interest approach, we found reduction in myelin in the whole cohort at the end of the hockey season compared to baseline.

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

We previously reported heterogeneous perfusion disruption beyond the impact area following mild TBI. However, it is unclear how such hemodynamic disruption affects tissue outcome. This study evaluated the effects of perfusion deficit on ADC, T2 and FA by analyzing a series of ROIs away from to the impact area. MRI parameters did not changed when CBF dropped to 60% of normal, but changed only when CBF dropped below 20% of normal at 1-3hrs and 2 days post TBI. CBF recovered on day 14 and so did FA, ADC and T2 values, suggesting that this mild TBI model induces reversible injury.

Iain David Croall¹, Christopher Cowie², Jiabao He³, Anna Peel¹, Joshua Wood¹, Benjamin Aribisala⁴, Patrick Mitchell², David Mendelow², Fiona Smith¹, David Millar⁵, Thomas Kelly², and Andrew Blamire^1
1Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, ²Newcastle upon Tyne Hospitals NHS Foundation Trust, Tyne and Wear, United Kingdom, ³Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Aberdeen, United Kingdom, ⁴Brain Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom, ⁵Neurocog, Tyne and Wear, United Kingdom

Diffuse axonal injury resulting from Traumatic Brain Injury (TBI) can be investigated using advanced MR techniques. While different modalities are specialised for specific analyses, little research has combined techniques. We present a joint Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy investigation examining mildly injured TBI patients at 6 days post-injury. Regarding the DTI findings, we present a new conclusion on the previously unusual and contentious finding of increased fractional anisotropy, while a novel result of increased N-acetylaspartate and evidence of creatine alterations post-injury are reported following Spectroscopy analysis. Additionally, these physical changes are correlated with measures of cognitive functioning.

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

The initial direct mechanical damage in traumatic brain injury (TBI) is followed by secondary damage that includes impaired cerebral blood flow, autoregulation, and metabolic function. The goal of this study was to longitudinally examine the vascular reactivity to CO2 in mild TBI during hyperacute and chronic phase up to 14 days. Extensive and severe CO2 reactivity disruption beyond the impact area was observed in hyperacute TBI. Area of CO2 response abnormality appeared much larger than CBF, T2, and ADC abnormality in the hyperacute phase. T2 and CO2 reactivity mostly normalized by day 14 but mild hypoperfusion and reduced CO2 reactivity remained on day 14. These multi-parametric MRI offers complementary, clinically relevant information.

Robert Johnstone^1,2, Katalin Povázai³, Jonathan Ashmore⁴, Nicholas Byrne^2,3, Sarah Peel^2,3, Ata Siddiqui³, Jean-Marie U-King-Im³, Denis Azzapardi², Andrew Kapetanakis³, and Geoff Charles-Edwards^1,2
1Guy's & St Thomas' NHS Foundation Trust, London, London, United Kingdom, ²King's College London, London, United Kingdom, ³Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom, ⁴King's College Hospital NHS Foundation Trust, London, United Kingdom

The presence of a doublet at 1.1 ppm in MRS is often attributed to the presence of propylene glycol, a widely used excipient. This work investigates the assumed direct relationship between administered PG and observed PG levels in MRS and finds a poor correlation between the two measurements. This suggests further work is required to elucidate the relevant of PG levels in MRS and their any clinical relevance.

Alan Bainbridge¹, Mojgan Ezzati², Kevin Broad², Go Kawano², Aaron Oliver-Taylor², Igor Fierens², Jamshid Rostami², Jane Hassell², Ilias Tachsidis³, Pierre Gressens⁴, Mariya Hristova⁵, Kate Bennett², Magdalena Sokolska⁶, Price David⁶, Bobbi Fleiss⁴, Derek Yellon⁷, Derek J Hausenloy⁷, Xavier Golay⁸, and Nicola J Robertson^2
1Medical Physics, UCLH NHS Foundation trust, London, United Kingdom, ²Institute for Women's Health, University College London, United Kingdom, ³Medical Physics, University College London, United Kingdom, ⁴Centre for the Developing Brain, Institute of Reproductive and Developmental Biology, Imperial College, United Kingdom,⁵Wellcome Centre for Imaging Neuroscience, University College London, United Kingdom, ⁶Medical Physics, UCLH NHS Foundation trust, United Kingdom, ⁷The Hatter Cardiovascular Institute, University College London, United Kingdom, ⁸Institute of Neurology, University College London, United Kingdom

Neonatal encephalopathy is associated with high mortality and morbidity rates worldwide. There is an unmet need to develop novel, non-invasive approaches, which can be used alone or in combination with hypothermia to augment neuroprotection. The aim of this study was to assess whether hind limb remote IPostC after transient hypoxia-ischaemia (HI) is neuroprotective based on 1H and 31P MRS cerebral biomarkers and immunohistochemistry in a piglet model of perinatal asphyxia. Remote IPostC was neuroprotective based on reduced WM Lac/NAA at 48h and reduced TUNEL positive cells in WM. Whole brain 31P MRS NTP/epp was preserved with remote IPostC.

Carlos C. Faraco¹, Lindsey M. Dethrage¹, Meaghan A. Neill², Lori C. Jordan³, Robert J. Singer⁴, J Mocco⁵, Paul F. Clemmons⁶, Manus J. Donahue^1,3, and Megan K. Strother^1
1Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ²The Medical University of South Carolina, Charleston, SC, United States, ³Department of Neurology, Vanderbilt University, Nashville, TN, United States, ⁴Section of Neurosurgery, Geisel School of Medicine at Dartmouth, Hanover, NH, United States, ⁵Department of Neurosurgery, Vanderbilt University, Nashville, TN, United States, ⁶Department of Radiology Nursing, Vanderbilt University, Nashville, TN, United States

Pre- and/or post-revascularization BOLD scans were acquired on non-atherosclerotic intracranial stenosis (i.e., Moyamoya disease) patients during hypercarbic hyperoxic (carbogen; 5% CO2 / 95% O2) vascular stimulation to demonstrate the effectiveness of BOLD fMRI to longitudinally monitor CVR. Patients with pre- and post-op scans continued to demonstrate significantly improved (p<.001) CVR in the operative hemisphere at the time of their second post-op scan (17±5 months post-op). When all patients’ scans were grouped by time after revascularization, significant (p<.001) improvements were seen beginning at approximately one year post-op and stabilized at approximately two years post-op.

Dewen Meng¹, Akram A. Hosseini¹, Richard J. Simpson¹, Robert A. Dineen¹, and Dorothee P. Auer^1
1Radiological Sciences,Division of Clinical Neurosciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Cognitive impairment is common in patients with cerebrovascular disease. The mechanisms underlying vascular cognitive impairment (VCI) have not been well established. Resting-state functional MRI has provided new insights on the functional connectivity (fc) of brain. The aim of this study was to assess fc abnormalities as potential neural substrate of cognitive impairment in patients with recently symptomatic carotid artery disease.Our findings show that VCI results from long range disconnection of the left hippocampus fc and default mode network, suggesting that fc assessed by resting-state fMRI has the potential to become a diagnostic marker that may also be useful for the assessment of treatment and rehabilitation.

Petra van Houdt¹, Britt Kunnen¹, Olga Hamming-Vrieze¹, Jeroen van de Kamer¹, and Uulke van der Heide^1
1Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands

This study presents a voxel-based comparison between FDG-PET and dynamic contrast-enhanced (DCE-) MRI for twenty-one patients with head-and-neck cancer. At voxel-level the correlations within the gross tumor volume were higher between SUV and Ktrans and kep compared to the correlations at patient-level. Therefore, it is important to take tumor heterogeneity into account.

Zhensen Chen¹, Huijun Chen¹, Aofei Liu², Wei-Jian Jiang², William Kerwin³, Chun Yuan^1,3, and Xihai Zhao^1
1Center for Biomedical Imaging Research & Department of Biomedical Engineering, Tsinghua University, Beijing, China, ²New Era Stroke Care and Research Institute, The Second Artillery General Hospital PLA, Beijing, China, ³Department of Radiology, University of Washington, Seattle, WA, United States

During stenting procedure of basilar artery (BA) atherosclerosis, the plaque may be pushed and block the ostia of the perforating arteries that usually originate from the lateral or dorsal walls of BA, thus causing severe ischemic events. Hence, assessment of BA plaque distribution is important prior to stenting. This study sought to develop a semi-automatic analysis tool to comprehensively evaluate plaque characteristics, particularly cross-sectional distribution, in 58 symptomatic patients. We found that >60% of BA plaques mainly affected lateral or dorsal walls, suggesting the necessity of evaluation of lesion distribution prior to treatment using 3D MR vessel wall imaging.

Manus Joseph Donahue¹, Lindsey Dethrage¹, Carlos Faraco¹, Lori Jordan¹, Paul Clemmons¹, and Megan K Strother^1
1Vanderbilt University, Nashville, TN, United States

Carbogen (i.e., 5%CO2/95%O2)-induced measures of CVR are potentially safer than measures elicited by other hypercarbic gas mixtures, owing to abilities of carbogen to increase oxygen delivery to tissue. However, carbogen adds additional complications owing to effects of transient hyperoxia on metabolism and increases in sPO2. Here, we applied a carbogen MRI protocol in intracranial stenosis patients (n=54). Findings demonstrate focal regions of CVR discrepancy between healthy and diseased hemispheres in patients, consistent with angiographic measures of impairment, however only when z-statistic markers of CVR are utilized. However, quantitative interpretation of absolute signal changes is altered by increases in blood [HbO2]/[Hb].

Thomas Christen¹, Hesamoddin Jahanian¹, Wendy Wei Ni¹, Deqiang Qiu¹, Michael E Moseley¹, and Greg Zaharchuk^1
1Department of Radiology, Stanford University, Stanford, California, United States

In this work, we compared perfusion maps obtained with resting-state BOLD fMRI (no contrast agent used) to perfusion maps obtained with Dynamic Susceptibility Contrast (Gadolinium contrast agent) in 20 patients with cerebrovascular diseases. We also derived connectivity maps from the same data and analyzed the influence of time delays on the results.

George William John Harston¹, Jacob Levman², Thomas Okell³, George Pope⁴, Ian Reckless⁴, Fintan Sheerin⁴, Martino Cellerini⁴, Stephen Payne², Michael Chappell², Peter Jezzard³, and James Kennedy^1
1Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²Department of Engineering Science, University of Oxford, Oxford, Oxfordshire, United Kingdom, ³Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom, ⁴Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, United Kingdom

Diffusion-weighted imaging, using the apparent diffusion coefficient (ADC), is the current imaging gold standard to define infarction acutely for patients with ischemic stroke. The natural history of this biomarker is debated and its validity in defining infarction has been challenged. In this study repeated measures of ADC were systematically taken from a cohort of patients with ischemic stroke to explore the changes of this biomarker over time. It was found that ADC lesion reversal within 24 hours does not predict sustained tissue recovery, but a small proportion of tissue with abnormal ADC at 24 hours will recover by 1 month.

Jamie M Kawadler¹, Fenella J Kirkham², Simon Barker³, Tim CS Cox⁴, and Chris A Clark^1
1Imaging & Biophysics Unit, UCL Institute of Child Health, London, United Kingdom, ²Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom, ³Wessex Neurological Centre, Southampton University Hospitals NHS Trust, Southampton, United Kingdom, ⁴Radiology, Great Ormond Street Hospital NHS Trust, London, United Kingdom

Sickle cell anaemia (SCA) is a genetic disorder affecting the oxygen-carrying capacity of haemoglobin. In children, overt and silent stroke are prevalent. In those with no apparent stroke on MRI, white matter (WM) abnormalities have been described, but links to disease-mediating factors (i.e. chronic anaemia and oxygen desaturation) are unknown. We performed a whole-brain voxel-wise WM analysis, finding anisotropy decreases in subcortical WM and increases in diffusivity widespread across the brain in patients compared to controls. We also found a trend correlation between lower daytime oxygen saturation and higher radial diffusivity in patients, which may have implications for oxygen therapy.

Zachary B Rodgers¹, Varsha Jain¹, Michael C Langham¹, Sarah Leinwand¹, Richard J Schwab¹, and Felix W Wehrli^1
1University of Pennsylvania, Philadelphia, PA, United States

It has been hypothesized that the repeated nocturnal apnea experienced by patients with obstructive sleep apnea (OSA) results in blunting of the normal neurovascular apneic response, causing repeated nocturnal hypoxia which manifests as neurologic comorbidities. In this study, a recently developed method for rapid MRI-based quantification of CMRO₂ was used to determine whether OSA results in reductions in resting-state CMRO₂ and the CMRO₂ response to apnea. Preliminary results, though not statistically significant, suggest OSA-associated reductions in both baseline and apneic CMRO₂.

Yi-Hsiu Hsiao¹, Yung-Chieh Chen², Cheng-Yu Chen^1,3, Shih-Wei Chiang^4,5, Hsiao-Wen Chung⁵, Ping-Huei Tsai¹, Ming-Chung Chou⁶, Hung-Wen Kao⁴, and Chao-Ying Wang^4
1Department of Medical Imaging and Imaging Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ²Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ³Graduate Institue of Clinical Medicine, Taipei Medical University, Taipei, Taiwan,⁴Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan, ⁵Graduate Institute of Biomedical Electrics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ⁶Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan

Thalamus plays a pivot role in the process of rebuilding the circuitry after MCA stroke by neuro-adaptation called plasticity. One previous study has demonstrated that, by using diffusion tensor imaging (DTI), an increase in mean diffusivity in thalamus was shown after MCA infarct but fractional anisotropy (FA) remained unchanged. This study was limited by a lack of investigating the individual thalamic nucleus. Therefore, we aim to evaluate the changes of FA in the motor-sensory-related thalamic nuclei (VA, VL and VPL) in patients with MCA ischemic stroke at both acute and chronic stages using tract-based segmentation method.

Yuhao Sun^1,2, Qiang Shen¹, Shiliang Huang¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States, ²Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Vasospasm is a hallmark of human SAH and needs to be treated promptly. Similar animal MRI studies of vasospasm in SAH are sparse. Moreover, SAH’s effects on veins remain unknown in SAH patients and animal models of SAH. This study investigated the effects of SAH on cerebral arteries and veins in rats using MRA and MRV. SAH caused severe time-dependent arterial vasospasm. SAH also increased venous volume, impeding vein reflux. These changes likely play a role in early brain injury in SAH. Our studies point to an additional and underappreciated set of physiologic effects that are caused by subarachnoid hemorrhage.

Graeme A Deuchar¹, David Brennan², William M Holmes¹, Maria del Rosario Lopez Gonzalez¹, Martin Shaw³, I Mhairi Macrae¹, and Celestine Santosh^2
1Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, United Kingdom, ²Institute of Neurological Sciences, Southern General Hospital, Glasgow, United Kingdom, ³Clinical Physics, University of Glasgow, Glasgow, United Kingdom

Thrombolysis, the only licensed therapy for acute stroke remains under-utilised due to safety concerns concerning its use beyond the 4.5hr “treatment-window” Improved brain imaging would enable safer and wider treatment by identifying patients with salvageable brain tissue (penumbra) who would benefit from thrombolysis regardless of time. Existing imaging is inadequate and lacks diagnostic validation. GOLD (Glasgow-Oxygen-Level-Dependent) imaging uniquely employs MRI, hyperoxia and an oxygen-carrier perfluorocarbon (Oxycyte®) to enhance metabolic differentiation of penumbra from irreversibly damaged tissue thereby providing clinicians with a stratified measure of tissue viability while also supporting penumbra survival through improved oxygenation (additional imaging time carries no penalty).

Erin L Mazerolle¹, Roberta La Piana², Donatella Tampieri², Kelvin Mok², Maria Cortes², Denise Klein², and G Bruce Pike^1
1University of Calgary, Calgary, Alberta, Canada, ²Montreal Neurological Institute, Montreal, Quebec, Canada

Pre-treatment mapping has become an established clinical application of blood oxygen level dependent (BOLD) fMRI. However, in patients with abnormal perfusion such as arteriovenous malformations (AVMs), it can be difficult to interpret BOLD results. We used arterial spin labelling (ASL) to evaluate whether perfusion information can clarify the interpretation of atypical fMRI responses in AVM patients. We found that atypical BOLD functional connectivity and activation was preferentially localized to regions of abnormally high perfusion. We propose that clinical applications of BOLD in patients with abnormal cerebral hemodynamics could greatly benefit from additional measurements such as ASL.

Harshan Ravi^1,2, Binu P Thomas^1,2, Shin-lei Peng¹, and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical center, Dallas, Texas, United States, ²Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, United States

With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. The increase in CVR with CO2 inhalation is an expected outcome, however recent studies reported apparent negative CVR. This apparently negative CVR is predominantly located in brain ventricles. This is attributed to a dilation of blood vessels during CO2 inhalation, which displaces the bright CSF signal in ventricle causing an “artifactual” reduction in BOLD signal. In this work, we performed simulation and experimental studies to re-optimize the BOLD imaging parameters such that negative CVR is removed.

Jeong Pyo Son¹, Suk Jae Kim², Sookyung Ryoo², Mi-Ji Lee², Jihoon Cha³, and Oh Young Bang^1,2
1Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea, ²Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, ³Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Assessing the status of collateral circulation is important in acute ischemic stroke. However, digital subtraction angiography (DSA) which is considered as the gold standard for evaluation of collaterals is invasive and has a risk of thrombotic complications. In this study, we developed a novel MRI technique for evaluation of collateral flow which can be generated using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) source data. This technique may provide insight on collateral perfusion in patients who are not otherwise candidates for conventional angiography and may potentially replace it in the future.

Kevin Murphy¹, Richard J.S. Wise², and Fatemeh Geranmayeh^2
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²Computational Cognitive and Clinical Neuroimaging Laboratory, Imperial College London, United Kingdom

BOLD fMRI is a widely used technique to map brain function and monitor its recovery after stroke. Impairments in cerebrovascular reactivity (CVR) will alter neurovascular coupling causing BOLD interpretability problems. This study demonstrates that CVR can be measured successfully using a breath-hold task in a stroke population. Reduced CVR in the stroke penumbra limits the interpretability of the BOLD signal in that area in comparisons with controls. However, since CVR in the penumbra remains unchanged over time, a finding of increased penumbral activity in a longitudinal study is less likely to be due to changes in vascular reactivity.

Vince Istvan Madai^1,2, Federico C von Samson-Himmelstjerna^1,3, Florian Weiler³, Nora Sandow⁴, Matthias Günther³, Peter Vajkoczy⁴, Thoralf Niendorf⁵, Jens Wuerfel^6,7, and Jan Sobesky^1,2
1Centre for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ²Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ³Fraunhofer-Mevis, Bremen, Germany, ⁴Department of Neurosurgery, Charité Universitätsmedizin Berlin, Berlin, Germany, ⁵Berlin Ultrahighfield Facility (B.U.F.F.), Max Delbrück Centrum (MDC), Berlin, Germany, ⁶Neurocure Clinical Research Centre, Charité Universitätsmedizin Berlin, Berlin, Germany, ⁷Department of Radiology, Universität Göttingen, Göttingen, Germany

MPRAGE imaging at 7T allows for the generation of intracranial angiographies (MRA). This is promising as TOF at 7T is limited owing to SAR-constraints. To be of clinical value, however, 7T MPRAGE-MRA has to offer at least the diagnostic level of the highest current clinical standard, e.g. TOF-MRA at 3T. In the present work, we analyzed 16 patients with cerebrovascular disease (stroke and moya-moya-disease) at 3T and 7T. We could show that 7T MPRAGE offers a diagnostic quality comparable to 3T TOF. This is promising, as high-resolution anatomic and vascular imaging could be performed using a single sequence at 7T.

Wenjia Peng^1,2, Zhongzhao Teng^2,3, Adam J Brown⁴, Jianmin Yuan², Qi Liu¹, Jonathan H Gillard², and Jianping Lu^1
1Department of Radiology, Changhai Hospital, Shanghai, Shanghai, China, ²University Department of Radiology, University of Cambridge, Cambridge, United Kingdom,³Department of Engineering, University of Cambridge, Cambridge, United Kingdom, ⁴Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom

Intracranial atherosclerosis is a major substrate for stroke, accounting for 5-10% of strokes in western societies and 33-55% of strokes in Asian populations. Plaque wall MR imaging is capable of depicting high risk morphological and compositional features, such as intraplaque hemorrhage and fibrous cap rupture. However, it is unclear if this technique could provide complementary information to lumen stenosis to discriminate clinical presentation in patients with middle cerebral artery (MCA) atherosclerotic disease. The result obtained in this study indicated that high-resolution MCA plaque wall imaging using 2D Turbo MR sequences provided limited additional value to luminal stenosis.

Olivia Sobczyk¹, Adrian Crawley², Julien Poublanc², Kevin Sam^2,3, Daniel M. Mandell², David Mikulis², James Duffin^3,4, and Joseph Fisher^3,4
1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, ²Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada,³Department of Physiology, University of Toronto, Toronto, Ontario, Canada, ⁴Anaesthesiology, University Health Network, Toronto, Ontario, Canada

Cerebrovascular reactivity (CVR), measured as the cerebral blood flow (e.g. BOLD MRI) response to a vasoactive stimulus (e.g. carbon dioxide), has been used to gauge neurovascular function. Despite uniform test conditions, between-test differences in CVR remain due to variations in normal physiology and in the measurement technology over time. We score test-to-test changes in CVR as the z-value derived from those of a cohort of healthy subjects tested on the same scanner. We demonstrate this approach identifies changes between tests that are unlikely to be attributed to physiology and technical variation, and thus attributed to interval change in pathology.

Mark Krongold^1,2, Mohammed Almekhlafi^1,2, Andrew Demchuck^1,3, Richard Frayne^1,2, and Armin Eilaghi^1,2
1Department of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ²Seaman Family MR Centre, Foothills Medical Centre, Calgary, Alberta, Canada, ³Calgary Stroke Program, Foothills Medical Centre, Calgary, Alberta, Canada

Our goal was to characterize infarct volume evolution over time with focus on the first 30 days post stroke. We screened 964 ischemic stroke patients and included 59 patients who had baseline DWI infarction and ≥2 FLAIR follow up imaging sessions. We show that the final infarct volume can be predicted after the first week. Recanalization status and baseline infarct volume significantly effect infarct expansion pattern and infarct volume size. These findings can potentially maximize recruitment in clinical trials, decrease needed follow up imaging sessions, and improve stroke management.

Christian Federau¹, Suna Sumer², Fabio Becce¹, Kieran O'Brien³, Reto Meuli¹, and Max Wintermark^2
1Radiology, CHUV, Lausanne, Vaud, Switzerland, ²Neuroradiology Division, Department of Radiology, University of Virginia, Charlottesville, Virginia, United States, ³Center for Biomedical Imaging (CIBM), University of Geneva, Geneva, Switzerland

In the setting of acute ischemic stroke, currently used perfusion methods (DSC and CTP) may fail to properly take into account leptomeningeal collateral blood flow supply, which is essential for clinical prognosis. Perfusion measurement using IVIM might theoretically solve this issue, as it is thought to be mainly dependent on the local microvascular perfusion. We present our initial clinical experience in 17 cases of acute brain strokes (< 6 days), demonstrating that the perfusion fraction f is significantly reduced in the infarcted area.

Thomas P Hansen¹, John Cain¹, Nitin Purandare², Owen Thomas³, and Alan Jackson^1
1Wolfson Molecular Imaging Centre, University of Manchester, Manchester, Lancashire, United Kingdom, ²Greater Manchester Old Age Psychiatry Service, University of Manchester, Manchester, Lancashire, United Kingdom, ³Department of Neuroradiology, Salford Royal NHS Hospitals Foundation Trust, Manchester, Lancashire, United Kingdom

We examine the discriminative power of the related perivascular spaces (PVS) in an elderly population of patients with vascular dementia, Alzheimer’s dementia and age-matched normal controls. We compare to previously described PVS scoring systems. The discriminative power standard white-matter scoring systems and PBS are modelled using non-linear regression. We demonstrate that PVS scores have greater significant independent discriminative power for the separation of VaD from normal and AD subjects than white matter hyper intensity scoring systems.

Neil Chatterjee^1,2, Parmede Vakil^1,2, Shyam Prabhakaran¹, Sameer Ansari¹, Michael Hurley¹, and Tim Carroll^1,2
1Northwestern University Feinberg School of Medicine, Chicago, IL, United States, ²Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States

MR perfusion imaging has become an important tool in the assessment of cerebrovascular disease. A commonly used technique to quantify MR perfusion results is to have a physician manually draw ROIs in different vascular territories, but this is a time consuming and subjective process that can introduce bias. Here we propose a method for automatically constructing subject-specific vascular territory ROIs and validate the method in cohorts of ischemic stroke patients and healthy volunteers.

Jin Wook Choi¹, Miran Han¹, Sun Yong Kim¹, and Nae Jung Lim^1
1Radiology, Ajou University School of Medicine, Suwon, Gyunggido, Korea

Arterial dissection is a significant cause of stroke in younger patients. A safe and feasible tool for early diagnosis is needed to prevent neurologic sequelae. Direct imaging findings of dissection were well visualized by HR-MR imaging, and detection of a dissection flap on CE-T1WI is the most diagnostic finding. HR-MR imaging could be a useful and non-invasive diagnostic tool for diagnosis of arterial dissection involving the intracranial vertebrobasilar system.

Olivia Sobczyk^1,2, Daniel M. Mandell², Kevin Sam^2,3, Adrian Crawley², Julien Poublanc², David Mikulis², James Duffin^3,4, and Joseph Fisher^3,4
1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, ²Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada,³Department of Physiology, University of Toronto, Toronto, Ontario, Canada, ⁴Anaesthesiology, University Health Network, Toronto, Ontario, Canada

We used cerebrovascular reactivity (CVR), the change in cerebral blood flow, as measured using BOLD MRI in response to a hypercapnic vasodilatory stimulus to test neurovascular reserve. We scored CVR values voxel-by-voxel in terms of statistical differences from the corresponding voxel in a cohort of healthy subjects. We averaged the z-scores in the MCA territories in a cohort of patients with steno-occlusive disease and in healthy subjects. Frequency distribution histograms showed only a small overlap in average z-values between patients and healthy subjects suggesting this analysis may be a sensitive and specific objective discriminator for steno-occlusive disease.

Lise Magnollay¹, Francesco Grussu^2,3, Claudia A.M. Wheeler-Kingshott², Varun Sethi², Hui Zhang³, Declan Chard^2,4, David H. Miller^2,4, and Olga Ciccarelli^1,4
1NMR Research Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, ²NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, ³Department of Computer Science and Centre for Medical Image Computing, UCL, London, United Kingdom, ⁴NIHR UCL-UCLH Biomedical Research Centre, London, United Kingdom

Neurite Orientation Dispersion and Density Imaging (NODDI) provides information about orientation dispersion (ODI) and neurite density (NDI) of the underlying tissue. We applied NODDI to single-shell brain diffusion-weighted imaging of relapsing-remitting MS patients and healthy controls. Patients showed (i) lower ODI in the internal capsules and genu of the corpus callosum than controls, (ii) lower NDI in the genu of the corpus callosum and right occipital cortex than controls, (iii) higher FA in the right internal capsule than controls. In patients, lower occipital cortex NDI correlated with longer disease duration. Therefore, NODDI parameters reflect tissue abnormalities not detectable with FA.

Yunyan Zhang¹, Bailey Komishke², Luanne Metz³, and Lenora Brown^3
1University of Calgary, Calgary, AB, Canada, ²University of British Columbia, BC, Canada, ³University of Calgary, AB, Canada

To understand the mechanism relating to distinct disability, we evaluated both macroscopic and microscopic tissue change in advanced SPMS and mild RRMS, with a focus on the corpus callosum. We found smaller white matter volume, not gray matter, in SPMS than in RRMS subjects but similar T2 lesion load. Also in SPMS, corpus callosum was atrophic, where fractional anisotropy and radial diffusivity was significantly compromised. No difference between mild RRMS and controls. Our results suggest the importance of NAWM and early intervention may protect mild RRMS patients from developing advanced disability.

Katherine A Koenig¹, Ken E Sakaie¹, Mark J Lowe¹, Jian Lin¹, Erik B. Beall¹, Stephen M Rao², Lael Stone², Robert Bermel², Bruce D Trapp³, and Micheal D Phillips^1
1Imaging Sciences, The Cleveland Clinic, Cleveland, OH, United States, ²Neurological Institute, The Cleveland Clinic, Cleveland, OH, United States, ³Neurosciences, The Cleveland Clinic, Cleveland, OH, United States

The current work uses DTI tractography to investigate the integrity of the posterior cingulate-entorhinal cortex in 57 subjects with Multiple Sclerosis (MS) and 17 controls. Subjects with MS showed pathologic DTI measures, and all DTI measures were related to measures of spatial episodic memory.

Thomas Welton¹, Dorothee Auer¹, and Rob Dineen^1
1Radiological Sciences Group, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Relevance of tract-specific white matter degradation to clinical and cognitive functional status in multiple sclerosis (MS) has been a focus of recent research, but a consensus is yet to emerge. We present the first voxelwise meta-analysis of tract-based spatial statistics studies in MS, incorporating data across 8 studies and 358 patients. Our findings confirm widespread reductions in tract FA in MS patients in comparison to controls. Damage to white matter tracts in the corpus callosum and posterior cingulum was associated with elevated disability and cognition.

Wenshu Qian¹, Koon-Ho Chan², Mina Kim¹, and Henry Ka-Fung Mak^1
1Diagnostic Radiology, The University of Hong Kong, Hong Kong, China, ²Medicine, The University of Hong Kong, Hong Kong, China

Early diagnosis and differentiation of neuromyelitis optica (NMO) from multiple sclerosis (MS) is vital to provide timely and proper treatment. However, conventional MRI techniques are not sensitive to assess the occult microstructural changes in brain tissues in the early or stable stage. In this study, we investigated the normal-appearing white matter and cortical gray matter in controls and patients with NMO and MS using diffusion kurtosis imaging (DKI). Our results demonstrate that DKI-derived indices are sensitive to detect the microstructural abnormalities and can distinguish pathological alterations in NMO from MS, suggesting DKI may be a useful diagnostic tool of NMO.

Günther Grabner¹, Assunta Dal-Bianco², Hans Lassmann³, Siegfried Trattnig¹, and Simon Hametner^3
1MR Centre of Excellence, Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Neurology, Medical University of Vienna, Vienna, Austria, ³Center for Brain Research, Medical University of Vienna, Vienna, Austria

Susceptibility-Weighted-Imaging allows high resolution imaging of the venous system. However, the real size of the imaged veins remains unknown. The purpose of this study was to determine the relation between apparent SWI vessel sizes and real vessel diameters measured on histological tissue. Two in-vitro SWI acquisitions were performed, one on a healthy and one on a multiple sclerosis brain. Furthermore we compared the SWI enlargement factor in healthy brain tissue to the MS brain. Results indicate an SWI enlargement factor of about 3.7 for vessels with a histological diameter below 100 µm independently from disease status.

Matthew P Quinn^1,2, Marcelo Kremechutzky³, and Ravi S Menon^1,2
1Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, ²Medical Biophysics, Western University, London, Ontario, Canada,³Clinical Neurological Sciences, Western University, London, Ontario, Canada

Visualizing white matter hyperintensities (WMHs) with MRI is a critical step in diagnosing multiple sclerosis (MS), but WMHs are also present in other diseases. The presence of central veins within WMHs may be specific to MS. In this study, healthy controls (HCs) and patients with clinically isolated syndromes (CIS) suggestive of MS were imaged with FLAIR (to identify WMHs) and SWI (to identify veins). After clinical follow up, it was determined that all CIS patients who were diagnosed with MS within the 11 month study window had more than 40% lesions with central veins at clinical presentation.

David A. Rudko^1,2, Igor Solovey², Joseph S. Gati², Marcelo Kremenchutzky³, and Ravi S. Menon^2
1Department of Physics and Astronomy, University of Western Ontario, London, Ontario, Canada, ²Robarts Research Institute, Centre for Functional and Metabolic Mapping, London, Ontario, Canada, ³Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada

Conventional MRI measures of multiple sclerosis (MS) disease status, using the number and location of lesions in white matter have not correlated well with clinical symptoms or demonstrated significant predictive power for understanding disease progression. The purpose of this study was to evaluate quantitative susceptibility (QS) and apparent transverse relaxation rate (R₂^*) mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in MS. QS and R₂^* maps acquired using 7T gradient echo MRI identified demyelination and iron accumulation in MS that correlated strongly with clinical disability. Using this information may allow earlier administration of therapies and monitoring of MS pathology in-vivo.

Sanjeev Chawla¹, Ilya Kister², Robert I Grossman¹, and Yulin Ge^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²Neurology, New York University Langone Medical Center, New York, NY, United States

The purpose of present study was to determine fiber degeneration along the course of corticospinal tract (CST) in a cohort of 33 patients with multiple sclerosis (MS) who alongwith 17 controls underwent diffusion tensor imaging. Significant reduction in fractional anisotropy (FA) and elevation in mean diffusivity (MD) alongwith trends towards increase in axial and radial diffusivities were observed in patients compared to controls. Combination of MD and FA provided sensitivity of 88.2% and specificity of 63.6% to distinguish two groups. A significant inverse correlation between FA and EDSS was observed. Our study demonstrates quantitative structural degeneration of CST in MS.

Viktor Wottschel^1,2, Daniel C. Alexander², Declan T. Chard³, Christian Enzinger⁴, Massimo Filippi⁵, Jette Frederiksen⁶, Claudio Gasperini⁷, Antonio Giorgio⁸, Maria A. Rocca⁵, Alex Rovira⁹, Nicola De Stefano⁸, Mar Tintoré⁹, David H. Miller³, and Olga Ciccarelli^1
1NMR Research Unit, Department of Brain Repair and Rehabilitation, Queen Square MS Centre, UCL Institute of Neurology, London, London, United Kingdom, ²Microstructure Imaging Group, Centre for Medical Image Computing, Department for Computer Science, UCL, London, London, United Kingdom, ³NMR Research Unit, Department of Neuroimflammation, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom, ⁴Department of Neurology and Section of Neuroradiology, Medical Unversity of Graz, Graz, Graz, Austria, ⁵Neuroimaging Research Unit, Vita-Salute San Raffaele University, Milan, Milan, Italy, ⁶Department of Neurology, Glostrup Hospital and University of Copenhagen, Copenhagen, Copenhagen, Denmark, ⁷Neurology Unit, San Camillo-Forlanini Hospital, Rome, Rome, Italy, ⁸Department of Neurological and Behavioral Sciences, University of Siena, Siena, Siena, Italy, ⁹Department of Radiology and Neuroimmunology Unit, Hospital Vall d'Hebron, Barcelona, Barcelona, Spain

We present a feasibility study predicting the time-to-conversion (in days) from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) using the machine learning technique random forests. T1 weighted baseline MRI data of 203 CIS patients from multiple European centres was spatially normalised and subdivided in 100 independent training and testing sets. From every training set an individual random forests was created consisting of 100 trees. The median error over all 100 bootstraps was 0.7 (range 0.57-1.16). Considering the slightly skewed data set and high similarity in T1 signal in the patient cohort, this is a very promising result.

Martijn D. Steenwijk¹, Marita Daams^1,2, Petra Pouwels³, Lisanne J. Balk⁴, Prejaas K. Tewarie⁴, Joep Killestein⁴, Bernard M.J. Uitdehaag⁴, Jeroen J.G. Geurts², Frederik Barkhof¹, and Hugo Vrenken^1,3
1Department of Radiology and Nuclear Medicine, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ²Department of Anatomy and Neurosciences, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ³Department of Physics and Medical Technology, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ⁴Department of Neurology, VU University medical center, Amsterdam, Noord-Holland, Netherlands

Gray matter (GM) atrophy is common in multiple sclerosis (MS), but the relation with white matter (WM) pathology is largely unknown. We aimed to identify the WM measures that explain whole brain GM, cortical and subcortical atrophy in a large cohort (n=208) of long-standing MS patients using stepwise linear regression. WM atrophy and lesion volume were the most important measures explaining whole brain and subcortical atrophy, while cortical atrophy was associated with NAWM integrity loss. The weaker relationship between GM atrophy and WM pathology in progressive patients might indicate a more independent neurodegenerative disease process in these patients.

K.A. Meijer¹, M. Cercignani², N. Muhlert¹, V. Sethi¹, D. Chard^1,3, M. Ron¹, A.J. Thompson^1,3, D.H. Miller^1,3, J.J.G. Geurts⁴, and O. Ciccarelli^1,3
1NMR Unit, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom, ²Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom, ³NIHR University College London Hospitals, Biomedical Research Centre, London, United Kingdom, ⁴Department of Anatomy and Neuroscience, VU University Medical Centre, Amsterdam, Netherlands

We investigated whether loss of white matter integrity is associated with cognitive dysfunction in secondary progressive (SPMS) patients using tract-based spatial statistics (TBSS). Cognitively impaired patients showed a more extensive loss of WM integrity than cognitively preserved patients; most pronounced differences were observed in the fornix, corpus callosum, forceps major, right inferior longitudinal fasciculus and right uncinate fasciculus. In patients, the DTI metrics of many of these tracts showed significant correlations with processing speed and visual memory processing, suggesting that disruption in these tracts may result in a disconnection syndrome which is responsible for cognitive impairment in MS.

Elisabeth Baumann^1,2, Lucy A. E. Matthews³, Anthony Traboulsee¹, Jacqueline Palace³, and Shannon Kolind^1
1Department of Medicine, University of British Columbia, Vancouver, BC, Canada, ²Jacobs University Bremen, Bremen, Germany, ³Oxford University and Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are clinically similar demyelinating diseases, however it has recently been found that each has distinct pathological characteristics. Illustrating these differences with MRI has proven challenging. We investigated the fraction of fast-relaxing signal (fM, thought to be linked to myelin) and T1 (influenced by total water content) in NMO, MS and control whole-brain. fM was decreased in NMO and MS white matter and MS grey matter. T1 was increased in MS and NMO white matter. No significant differences were found between diseases, but MS consistently demonstrated lower fM and higher T1 than NMO.

Joseph Kuchling¹, Ivan Bozin¹, Jan Dörr¹, Caspar Pfueller¹, Lutz Harms², Thoralf Niendorf³, Friedemann Paul¹, Tim Sinnecker¹, and Jens Wuerfel^4
1NeuroCure Clinical Research Center, Berlin, Berlin, Germany, ²Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ³Berlin Ultrahigh Field Facility (B.U.F.F), Max Delbrueck Center for Molecular Medicine, Berlin, Berlin, Germany, ⁴Institute of Neuroradiology, University Medicine Goettingen, Goettingen, Germany

Differences between primary progressive (PP) and relapsing remitting (RR) multiple sclerosis (MS) have been described, raising the question whether PPMS is part of the MS disease spectrum or a disease entity of its own. We addressed this issue by investigating RRMS and PPMS lesions using UHF-MRI with high spatial resolution resolution. However, gray and white matter lesions could not differentiate RRMS and PPMS regarding plaque morphology, distribution and appearance. Our findings support the hypothesis that PPMS is part of the MS disease spectrum and does not represent a disease entity of its own.

Veronica Popescu¹, Roel Klaver², Yvon Galis-de Graaf², Pieter Voorn², Dirk Knol³, Adriaan Versteeg¹, Geert Schenk², Frederik Barkhof¹, Helga E De Vries⁴, Hugo Vrenken^1,5, and Jeroen JG Geurts^2
1Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands, ²Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, ³Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands, ⁴Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands, ⁵Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands

In multiple sclerosis grey matter becomes atrophic. Atrophy correlates with disability and cognitive impairment. It is unknown which tissue component causes this atrophy. In a combined post-mortem MRI-histopathology study, five anatomical regions were systematically sampled from 11 brain donors with MS. After generalized estimating equations with false discovery rate correction two predictors survived: axonal density in the superior frontal gyrus and astrocytes numbers in the inferior frontal gyrus. Cortical atrophy seems predominantly driven by neuropilema changes and gliosis, and not by inflammation or demyelination. This points towards the need to intensify the search for neuroprotective medication in MS.

Blake Dewey¹, Pascal Sati¹, Snehashis Roy², Luisa Vuolo^1,3, Colin Shea¹, Dzung Pham², and Daniel S. Reich^1
1National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, United States, ²Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States, ³Departments of Neurology and Radiology, University of Florence, Florence, Italy

Automatic lesion segmentation is required for analyzing large datasets provided by multicontrast 3D high-resolution imaging of multiple sclerosis. Although several methods have been proposed for MRI at clinical field strength (3T and below), 7T imaging remains uninvestigated due to more severe image bias (B1 field inhomogeneities, etc.) that can deeply impact the results of the existing segmentation algorithms. In this study, we propose an optimized multicontrast 3D high-resolution acquisition protocol combined with the use of advanced nonlinear bias correction and the LesionTOADS algorithm to create robust image segmentation and lesion load quantification at 7T.

E Datta¹, A Zhu², E Crabtree², D Goodin², A Green², S Hauser², B Cree², and RG Henry^1,2
1Bioengineering, UC San Francisco, San Francisco, California, United States, ²Neurology, UC San Francisco, California, United States

Multiple Sclerosis is a neurodegenerative disease characterized by lesions resulting from inflammatory demyelination. The ratio of T2 and T1 brain scans provides a new metric that can be compared between controls and patients to observe changes in white matter integrity that correlate with clinical disability scores. Z-scores obtained from this comparison show correlations with T2 lesion volume along with clinical measures such as EDSS. Thus far, the T2/T1 z-score metric has shown itself to be a promising substitute for T2 lesion volume, which does not capture the varying degrees of disease in sclerotic tissue.

Clara Tabea Strunk^1,2, Lucy A.E. Matthews³, Anthony Traboulsee¹, Jacqueline Palace³, and Shannon Kolind^1
1Department of Medicine, University of British Columbia, Vancouver, BC, Canada, ²University of Osnabrück, Osnabrück, Germany, ³Oxford University and Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom

Neuromyelitis optica (NMO) clinically resembles multiple sclerosis (MS), but has a different mechanism of demyelination. Brain MRI studies have had difficulty distinguishing between diseases. Our goal was to determine whether differences in myelin or total water content, as measured with multi-component relaxation imaging, could be detected between NMO and MS in cervical spinal cord. Surprisingly, little difference was found between NMO and MS in spinal cord, although both were significantly altered compared to healthy controls. Differences in myelin and total water content were more easily detected between controls and MS or NMO in spinal cord than in brain.

Irene Margaret Vavasour¹, Shannon H Kolind², Alexander Rauscher¹, Roger Tam¹, Nicholas Seneca³, David Leppert³, Alex L MacKay^1,4, David KB Li¹, and Anthony L Traboulsee^2
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, ³F. Hoffmann-La Roche Ltd., Switzerland, ⁴Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada

This study compared the results obtained from 3 quantitative MRI measurements (magnetization transfer ratio (MTR), myelin water fraction (MWF) and fraction of myelin signal from steady state imaging (fM)) in white matter from subjects with MS and healthy controls. The 3 putative myelin MRI markers demonstrate reduction across structures in MS compared to controls however, MWF demonstrated the largest decreases and range of differences between structures. All 3 metrics followed the same pattern showing the greatest decreases in the ILF, followed by the CC, SLF, MN and finally CST. The strongest correlation between metrics was found between MWF and fM.

Cheng Li¹, Alan C. Seifert¹, Suzanne L. Wehrli², Michael J. Wilhelm³, David B. Hackney⁴, and Felix W. Wehrli^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²NMR Core Facility, Children’s Hospital of Philadelphia, Philadelphia, PA, United States, ³Chemistry, Temple University, Philadelphia, PA, United States, ⁴Radiology, Harvard Medical School, Boston, MA, United States

Direct assessment of myelin would reveal central nervous system (CNS) abnormalities and enhance our understanding of neurological diseases. Our previous work demonstrated that myelin can be directly imaged on a 9.4T NMR laboratory spectrometer/imaging system with ultra-short echo time (UTE) imaging. However, the extremely short T2 values (~100s) and relatively low proton density of myelin limit its detectability on clinical scanner. In this work, we demonstrate the feasibility of quantitative zero-echo time (ZTE) imaging of reconstituted extracted myelin and intact lamb spinal cord at 9.4T and on a 3T whole-body scanner.

Douglas A. C. Kelley¹, Angela Jakary², Roland Henry³, Sarah J Nelson², and Daniel B Vigneron^2
1Neuro Apps and Workflow, GE Healthcare, Corte Madera, CA, United States, ²Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ³Neurology, UCSF, San Francisco, CA, United States

T1 weighted Zero Echo Time (ZTE) imaging at 7T with phased array coils provides improved depiction of cortical and subcortical multiple sclerosis (MS) lesions and surrounding tissue. In equivalent scan times to conventional methods, the sequence provides more uniform grey-white contrast, allowing improved delineation of cortical structures in addition to providing clear depiction of MS lesions and fast relaxing tissues within the brain. Images acquired with both conventional and ZTE inversion recover prepared sequences in several MS patients are compared.

Rexford Newbould^1,2, Charlotte Thomas³, Rebecca Quest⁴, Jean Lee³, Lesley Honeyfield⁴, Alessandro Colasanti^1,3, Paul Matthews^3,5, Adam Waldman⁴, and Paolo Muraro^3,6
1Imanova Centre for Imaging Sciences, London, United Kingdom, ²Experimental Medicine, Imperial College London, London, United Kingdom, ³Brain Sciences, Imperial College London, London, United Kingdom, ⁴Imaging, Imperial College London, London, United Kingdom, ⁵Neurosciences, GlaxoSmithKline R&D, London, United Kingdom, ⁶Clinical Neurosciences, Imperial College London, London, United Kingdom

MT saturation per TR (MTsat) has been proposed as a more quantified measure of magnetization transfer than MTR. Here, we acquired MTsat and MTR maps in 38 MS subjects and 13 healthy controls, outlined white and grey matter lesions on co-registered MPRAGE and T2w-FLAIR volumes. Both MT contrasts highlighted T1 and T2-visible lesions well. Normal-appearing white matter in controls and MS subjects did not differ in the MTR maps, but did strongly in MTsat maps. MTsat might be highlighting early NAWM degeneration in these MS subjects.

Mihael Varosanec¹, Dana Horakova², Jesper Hagemeier¹, Niels Bergsland¹, Michaela Tyblova², Zdenek Seidl³, Manuela Vaneckova³, Jan Krasensky³, Michael G. Dwyer¹, Eva Havrdova², and Robert Zivadinov^1
1Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo SUNY, Buffalo, NY, United States, ²Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, Prague, Czech Republic, ³Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic

We investigated accumulation of new brain lesion, lesion volume, and contrast enhancing lesions with respect to the atrophy of gross brain structures in patients with clinically isolated syndrome. Longitudinal linear and quadratic mixed effect model analyses were performed for each time point and in dual directions. The more robust inverse mixed-effect model results suggest that the level of brain atrophy can explain T2 lesion accumulation better than the T2 lesion accumulation can explain accumulation of brain atrophy. These results suggests that close monitoring of brain volume changes may be relevant for identifying patients at risk for MS conversion.

Gopal Varma¹, Mohit Neema², Fotini S Papadopoulou¹, Shahamat Tauhid², Rohit Bakshi², and David C Alsop^1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

The apparent specificity of inhomogeneous magnetization transfer (IHMT) to myelinated tissue lends itself to study in pathologies related to myelin loss. A preliminary results from IHMT applied in patients with multiple sclerosis (MS) are reported. A statistically significant difference is found from the IHMT ratio in comparison with a group of healthy volunteers for a posterior region of interest. The difference within this region is less significant in analysis of the more commonly used MT ratio. IHMT might therefore provide a potential improvement over MT in analysis of MS and other myelin related diseases.

Guillaume Bonnier^1,2, Alexis Roche^1,3, David Romanasco⁴, Samanta Simioni², Djalel-Eddine Meskaldji⁴, David Rotzinger³, Ying-Chia Lin⁵, Gloria Menegaz⁵, Myriam Schluep², Renaud Du Pasquier², Tilman Johannes Sumpf⁶, Jens Frahm⁶, Jean-Philippe Thiran⁴, Gunnar Krueger^1,7, and Cristina Granziera^1,2
1Advanced Clinical Imaging technology group, Siemens-CIBM, EPFL, Lausanne, Vaud, Switzerland, ²Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Vaud, Switzerland, ³Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Vaud, Switzerland, ⁴STI / IEL / LTS5, EPFL, Lausanne, Vaud, Switzerland, ⁵Dept. of Computer Science, University of Verona, Itlay, Italy, ⁶Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany, Germany, ⁷Healthcare Sector IM&WS S, Siemens Schweiz AG, Lausanne, Vaud, Switzerland

Conventional magnetic resonance imaging (MRI) measures of multiple sclerosis patients provide limited information about the nature and the extent of brain damage and repair. We established a clinically compatible protocol including quantitative MRI techniques (qMRI, T1, T2, T2* relaxometry) and semiquantitative Magnetisation Transfer Imaging to provide a comprehensive MRI fingerprint (CMF) of lesions that is more adherent to the real underlying pathology and to assess the CMF contribution to clinical performances in patients. Lesions characteristics, revealed by combination of q/sq MRI, highly correlated with patients clinical performance and more severe lesions appeared to drive the clinic-radiological correlations.

Sanjeev Chawla¹, Ilya Kister², Robert I Grossman¹, and Yulin Ge^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²Neurology, New York University Langone Medical Center, New York, NY, United States

To evaluate changes in perfusion parameters from deep gray matter regions, 15 patients with multiple sclerosis (MS) underwent dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) twice at an interval of 2 years in a longitudinal study. Using one tailed paired t-tests, significant elevation in relative cerebral blood volume (rCBV) and flow (rCBF) were observed from thalami at follow-up period compared to baseline probably secondary to inflammatory activities. Additionally, significant elevation in rCBF and reduction in relative mean transit time were observed from basal ganglia. Our preliminary findings suggest that DSC-PWI may be valuable in detecting follow-up hemodynamic impairment in MS.

Guillaume Bonnier^1,2, Alexis Roche^1,3, David Romanasco⁴, Samanta Simioni², Djalel-Eddine Meskaldji⁴, David Rotzinger³, Ying-Chia Lin⁵, Gloria Menegaz⁵, Myriam Schluep², Renaud Du Pasquier², Tilman Johannes Sumpf⁶, Jens Frahm⁶, Jean-Philippe Thiran⁴, Gunnar Krueger^1,7, and Cristina Granziera^1,2
1Advanced Clinical Imaging technology group, Siemens-CIBM, EPFL, Lausanne, Vaud, Switzerland, ²Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Vaud, Switzerland, ³Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Vaud, Switzerland, ⁴STI / IEL / LTS5, EPFL, Lausanne, Vaud, Switzerland, ⁵Dept. of Computer Science, University of Verona, Itlay, Italy, ⁶Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany, Germany, ⁷Healthcare Sector IM&WS S, Siemens Schweiz AG, Suisse, Switzerland

Conventional magnetic resonance imaging (MRI) of patients with multiple sclerosis provides only limited insights into the nature of brain tissue damage with modest clinical-radiological correlations. In this study, quantitative and semi-quantitative MRI techniques (T1, T2, T2*, MTR) were applied to study the potential of the MRI-accessible microstructural information to predict cognitive and motor scores in patients. A multiparametric analysis of whole brain abnormalities showed that MRI measures of microstructural alterations lead to significant improvement in clinical-radiological correlations even in the presence of minor functional deficits.

Katharina Müller¹, Joseph Kuchling¹, Ivan Bozin¹, Jan Dörr¹, Caspar Pfueller¹, Lutz Harms², Thoralf Niendorf³, Friedemann Paul¹, Tim Sinnecker^1,4, and Jens Wuerfel^1,5
1Neurocure Research Center, Berlin, Berlin, Germany, ²Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ³Berlin Ultrahigh Field Facility (B.U.F.F), Max Delbrueck Center for Molecular Medicine, Berlin, Berlin, Germany, ⁴Asklepios Fachklinikum Teupitz, Brandenburg, Germany, ⁵Institute of Neuroradiology, University Medicine Goettingen, Goettingen, Germany

Vascular alterations in multiple sclerosis (MS) have been described decades ago. T2* weighted ultrahigh field MRI at 3 Tesla (T) visualized shrinked brain veins within MS plaques in vivo. However, this observation may be influenced by partial volume effects. We addressed this issue by developing a novel quantification algorithm and a novel MR-post processing procedure that generates susceptibility weighted turbo inversion recovery magnitude (sTIRM) images. We observed less intralesional venous shrinking on sTIRM compared to T2* weighted FLASH imaging. Our results confirm initial reports showing venous shrinking within MS lesions that is probably not as severe as expected.

Enedino Hernández-Torres¹, Lindsay Machan¹, Dessa Sadovnick², Nancy Martin¹, Warren Perera¹, Anthony L Traboulsee^2,3, David Li¹, and Alexander Rauscher^1
1Radiology, UBC, Vancouver, BC, Canada, ²MS Clinic, UBC, Vancouver, BC, Canada, ³Neurology, UBC, BC, Canada

It has been suggested that multiple sclerosis may be associated with changes in the brain's draining veins. In this study we investigated the existence of those changes using time resolved MR angiography in three different groups: patients with MS, their healthy siblings and unrelated controls. We analyzed the cerebral circulation times for the three groups and did not find significant differences between the different groups (p>0.2). The results obtained suggests that drainage abnormalities are not characteristic for MS.

Stig Praestekjaer Cramer^1,2, Helle Simonsen¹, Signe Modvig², Jette Lautrup Frederiksen², and Henrik BW Larsson^1
1FI-Unit, Department of Diagnostics, University of Copenhagen, Glostrup, Danmark, Denmark, ²Department of Neurology, University of Copenhagen, Glostrup, Danmark, Denmark

We measured permeability of the blood-brain-barrier with DCE_MRI in 32 patients at onset of Optic Neuritis and 17 matched healthy controls. We found significnatly higher permeability in normal appearing white matter ON patients compared to controls, and permeability was significantly correlated with biomarkers of inflammation and cell migration in the cerebrospinal fluid. In 50% of ON cases, the patient will later develop multiple sclerosis, and we found significant higher permeability in patients that where diagnosed with MS within one year after ON onset. These findings further emphasize the importance of BBB pathology in both ON and MS, and could be a supplementary prognostic marker for conversion from ON to MS.

Shu-Wei Sun^1,2, Christopher Nishioka³, Steven Kaspick⁴, Chen-Fang Chung⁴, JoAnn Park⁴, and Hsiao-Fang Liang^4
1Loma Linda University, Loma Linda, CA, United States, ²University of California, Riverside, Riverside, CA, United States, ³University of California, Riverside, CA, United States,⁴Loma Linda University, CA, United States

Retina ischemia caused axonal degeneration along optic nerve (ON) and tract (OT) of WldS and wild-type, while the damage was delayed in WldS. In WldS, ON and OT showed significant reductions of axial diffusivity in weeks 1 and 2, respectively, which provided us the time window of distinguished injure severity between the proximal (ON) and distal sections (OT) of RGC axons. Gd-T1WI and Evans blue both showed significant BBB leakage in RI-affected ON and OT beginning at week 1 in WldS mice. The remote BBB leakage may be observed in Gd-T1WI and may confuse the MS diagnosis.

Sebastian Domsch¹, Frederik Wenz², and Lothar Rudi Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Baden-Württemberg, Germany, ²Department of Radiation Oncology, Heidelberg University, Mannheim, Baden-Württemberg, Germany

The quantitative blood oxygenation level-dependent (qBOLD) approach, based on the tissue model, has facilitated promising in-vivo results using MRI. Thereby, the oxygen extraction fraction (OEF) is of great clinical interest providing a parameter for brain tissue viability or monitoring radio and chemo therapy. However, the qBOLD approach has not become clinically established yet due to numerous fit-parameters in the tissue model requiring high SNR or long measurement times clinically not available. In this work, a multi-parametric qBOLD approach is proposed to obtain robust OEF maps within clinical acquisition times using separate MR sequences to reduce the number of unknown fit-parameters.

Marek Allen¹, Valentina Tomassini², Nikolaos Petsas³, Marco Carni³, Emilia Sbardella³, Kevin Murphy¹, Patrizia Pantano³, Carlo Pozzilli³, and Richard Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Cardiff, United Kingdom, ²School of Medicine, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, Cardiff, United Kingdom, ³Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy

Cerebrovascular reactivity (CVR) is the capacity of blood vessels to increase blood flow to brain tissue, a process essential for preserved neurovascular coupling. Using breath hold-induced hypercapnia we aimed to investigate CVR in multiple sclerosis patients and the effect of interferon-beta treatment. We discovered a reduced reactivity in patients compared with healthy controls independent of distributed grey matter density reductions. This was reversed following commencement of interferon-beta1a treatment to a level comparable with controls. The effect of immunomodulation on CVR in patients suggests altered CVR is related to MS inflammatory activity and could indicate a marker for early therapeutic effect.

Katherine A Koenig¹, Ken E Sakaie¹, Mark J Lowe¹, Jian Lin¹, Erik B. Beall¹, Stephen M Rao², Lael Stone², Robert Bermel², Bruce D Trapp³, and Micheal D Phillips^1
1Imaging Sciences, The Cleveland Clinic, Cleveland, OH, United States, ²Neurological Institute, The Cleveland Clinic, Cleveland, OH, United States, ³Neurosciences, The Cleveland Clinic, Cleveland, OH, United States

We investigate functional activation during the encoding phase of an episodic memory task in 16 healthy controls and 32 multiple sclerosis (MS) patients, 16 with intact cognition and 16 with impaired episodic memory. MS patients with impaired episodic memory showed lower thalamic activation during encoding of correct words, and mean signal in the left thalamus was related to episodic memory performance and thalamic volume in MS patients but not controls. A larger sample and longitudinal measures are required to clarify the temporal relationship of functional activation, thalamic atrophy, and cognitive performance in MS.

Vanessa L Palmer^1,2, Sheryl L Herrera³, Jonathan D Thiessen⁴, Shenghua Zhu⁵, Richard Buist⁴, Xin-Mi Li⁶, and Melanie Martin^2,7
1Biomedical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada, ²Physics, University of Winnipeg, Winnipeg, Manitoba, Canada, ³Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada, ⁴Radiology, University of Manitoba, Winnipeg, Manitoba, Canada, ⁵Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, ⁶Psychiatry, University of Alberta, Edmonton, Alberta, Canada, ⁷Biomedical Engineering, Physics & Astronomy, Radiology, Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada

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

Istvan Pirko¹, Jeffrey Gamez¹, Pascal Alihnuii Atanga¹, Stephanie J LaFrance², Slobodan I Macura³, and Aaron J Johnson^2
1Department of Neurology, Mayo Clinic, Rochester, MN, United States, ²Department of Immunology, Mayo Clinic, Rochester, MN, United States, ³NMR Core Facility, Mayo Clinic, Rochester, MN, United States

Brain atrophy in MS is an important determinant of functional outcome, yet its pathogenesis remains unclear. Using a virally induced murine MS model, we determined that class I haplotype plays a major influence on atrophy development. Atrophy and disability are independent from each other in mouse strains that don’t develop persistent demyelination; however, atrophy and disability strongly correlate when chronic demyelination is present. Brain atrophy development is overall unrelated to and independent of demyelination, and is the consequence of axonal/neuronal loss. Remyelination results in axonal preservation, preserved disability, and lack of brain atrophy development in the studied model.

A. Elizabeth de Guzman^1,2, Jonathan Bishop¹, Jacob Ellegood¹, and Brian J, Nieman^1,2
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, ²Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Magnetization transfer (MT), susceptibility weighted (SW) and diffusion tensor (DT) MR imaging are commonly used techniques to study white matter damage in neurodegenerative diseases. Using these methods, we investigated the effects of cranial irradiation on white matter pathology in the mouse. Differences were detectable in many white matter structures using MT and SW, but not DT MRI. We hypothesize that dymelination plays a larger role in irradiation induced damage than axonal changes. In the future we will study the effect of myelin protection in this irradiation model, and see how this affects the imaging outcomes.

Alexandra Petiet¹, Marie-Stéphane Aigrot², and Bruno Stankoff^2,3
1Center for Neuroimaging Research, Brain and Spine Institute, Paris, Ile-de-France, France, ²UPMC / INSERM UMR975, Brain and Spine Institute Research Center, Paris, Ile-de-France, France, ³APHP, Tenon Hospital, Paris, Ile-de-France, France

Myelin is a component of the nervous system that is disrupted in multiple sclerosis, resulting in neuro-axonal degeneration. We investigated the longitudinal effect of chronic cuprizone-induced demyelination in the brain of treated vs untreated mice at 11.7T. Signal intensity ratios, T2 values, and diffusion metrics measurements showed significant and reversible modifications in the corpus callosum, the external capsule, the cerebellum, the caudate putamen, the thalamus, and the cortex of treated mice. These multimodal data will provide better understanding of the MR signal specificity for myelin assessment, and will be the basis to test therapies against gray matter demyelination.

Colin Shea¹, Pascal Sati¹, Joseph Guy¹, Emily Leibovitch¹, Steven Jacobson¹, Afonso Silva¹, and Daniel S. Reich^1
1NINDS, NIH, Bethesda, Maryland, United States

Subtraction MRI is a powerful tool to study new lesions in multiple sclerosis, however unique challenges exist for its application in marmoset models of disease because of the lack of equivalent image processing tools. We developed an automated method to segment new white matter lesions from PD and T2 weighted MRI in marmosets using a new brain tissue atlas, inhomogeneity correction, intensity normalization, subtraction, and object detection. Our method can robustly detect new lesions in serial scans which will enable further study of lesion evolution in marmoset models of multiple sclerosis.

Masaki Fukunaga^1,2, Makoto Masumura³, Shuichi Koda³, Tomokazu Shimonaga³, Ryuichi Nakamura³, Yuki Mori¹, and Yoshichika Yoshioka^1,2
1Biofunctional Imaging, IFReC, Osaka University, Suita, Osaka, Japan, ²Brain Functional Imaging Technologies, CiNet, NICT-Osaka University, Suita, Osaka, Japan, ³Asubio Pharma Co. Ltd., Kobe, Hyogo, Japan

Cuprizone is a mitochondrial toxin that induces apoptosis of oligodendrocytes and demyelination in the central nervous system, and is used for animal model of de- and re-myelination in multiple sclerosis. Recently, manganese enhanced MRI (MEMRI) is utilized to reveal the mechanisms of neuroinflammatory and neurodegenerative disorders, especially it enhances image contrast of the glial (astrocytes and microglia) activations in the pathological conditions. In this study, we investigated manganese contrast enhancement in cuprizone induced demyelinated mouse brain using 11.7T ultra high field MRI, and analyzed with histology and glial marker expressions.

Kathryn L West¹, Nathaniel D Kelm¹, Daniel F Gochberg², Robert P Carson³, Kevin C Ess³, and Mark D Does^1,4
1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University, TN, United States, ³Neurology, Vanderbilt University, TN, United States, ⁴Vanderbilt.University Institute of Imaging Science, Vanderbilt University, TN, United States

Myelin water imaging (MWI) by multi-exponential transverse relaxation (MET₂) and quantitative Magnetization Transfer (qMT) provide valuable information about myelin content and microstructure in white matter, yet have a known discord between measures. 3D high resolution imaging protocols allow for efficient whole brain evaluation of abnormal myelination in recently developed hypomyelinated mouse models. In addition, comparing MWF and PSR measures to histology can provide insight to better understand white matter microstructure.

Allen Q. Ye¹, Rodolfo Gatto^1,2, Ehsan Tavassoli², M. Andrea Buenaventura², Gerardo A. Morfini², and Richard L. Magin^1
1Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ²Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, United States

The cause of Huntington’s disease (HD) is well defined; however, the molecular mechanisms underlying these deficits remain unknown. In this abstract, we explore the use diffusion tensor imaging of double transgenic YFP-R6/2 mouse, which allows the direct visualization of HD through intrinsic fluorescent properties, in pre-symptomatic mice. Both diffusion tensor imaging and quantitative immunofluorescence studies showed differential degeneration of axonal fibers across the corpus callosum (CC) long before the development of HD-like motor symptoms.

Nabeela Nathoo¹, Dayae Jeong², Michael B. Keough³, Tad Foniok¹, V. Wee Yong³, and Jeff F. Dunn^1,4
1Radiology, University of Calgary, Calgary, Alberta, Canada, ²Rice University, Houston, Texas, United States, ³Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, ⁴Experimental Imaging Centre, University of Calgary, Calgary, Alberta, Canada

We used a focal demyelinating model in mouse spinal cord, with a known course of demyelination and remyelination, to assess if scalar measures obtained using diffusion tensor imaging (DTI) could detect demyelination. During the time point with maximal demyelination, radial diffusivity and mean diffusivity were elevated while fractional anisotropy was reduced. Anterior to the lesion, axial diffusivity was significantly reduced at the time point of maximal demyelination compared to the time point with ongoing remyelination, suggestive of axonal injury. Taken together, these results support the use of DTI to assess demyelination and axonal injury in spinal cord.

Ana Belen Martin-Recuero¹, Agi Krzyzanowska², Carlos Avendaño², Ania Benítez¹, Pilar Lopez-Larrubia¹, Gerardo Brioso¹, and Sebastian Cerdan^1
1IIBm, Consejo Superior de Investigaciones Científicas, Madrid, Spain, ²Anatomy, Medical School, Madrid, Spain

Cerebral inflammation underlies the most prevalent neurological disorders, including cancer, ischemia or neurodegeneration but current bioimaging methods are not able to distinguish unambiguously between the inflammatory component and the intrinsic pathology. We report here a novel decision support system which selects the MRI sequences more relevant for discriminating automatically pixel-by-pixel between the inflamed component and the healthy mouse brain. Our results correlate well with multi-parametric MRI calculation and immunostaining experiments. This method may improve the clinical workflow and the non-invasive assessment of inflammation.

Jing Guo¹, Juergen Braun², Dominique Berndt³, Carmen Infante-Duarte^3,4, Ingolf Sack¹, and Jason M. Millward^3,4
1Department of Radiology, Charite - Universitaetsmedizin Berlin, Berlin, Berlin, Germany, ²Department of Medical Informatics, Charite - Universitaetsmedizin Berlin, Berlin, Germany, ³Department of Medical Immunology, Charite - Universitaetsmedizin Berlin, Berlin, Germany, ⁴Experimental and Clinical Research Center, Charite-Universitaetsmedizin Berlin and the Max-Delbrueck Center for Molecular Medicine Berlin, Berlin, Germany

We applied MRE to study regional differences in viscoelasticity in normal and inflamed mouse brain. In normal mouse brain, we found that the posterior region (comprising cerebellum and brainstem) is softer than the anterior region in a midsagittal slice. We also examined the alterations in G' of the GKO mice where more cerebellum involvement is expected during EAE, we observed the reduction in G' during the course of disease and a significant increase in the ratio of G' between the posterior and anterior part of the brain at day 14, which may relate to the infiltration of immune cells.

Min-Hui Cui^1,2, Cristin D. Davidson³, Ziqin Yuan¹, Kwame Kyei¹, Steven U. Walkley³, and Craig A. Branch^1,2
1Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, United States, ²Radiology, Albert Einstein College of Medicine, Bronx, New York, United States, ³Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States

A mouse model of Niemann-Pick type C disease, a fatal inherited metabolic disorder, shows disease amelioration upon administration of miglustat, cyclodextrin, or a combination of both compounds. Here, we show preservation of white matter as evidenced by increased FA in two distinct brain regions, the corpus callosum and fimbria. Cyclodextrin and combination therapy provided greater benefit than miglustat alone, following suit with what we have observed in longevity and in reductions of stored cholesterol and glycosphingolipids within treated NPC1-/- mice.

Candida L Goodnough¹, Ying Gao², Xin Li², L. Henry Goodnough³, Chris A Flask^2,4, and Xin Yu^2
1Physiology, Case Western Reserve University, Cleveland, OH, United States, ²Biomedical Engineering, Case Western Reserve University, OH, United States, ³Pathology, Case Western Reserve University, oh, United States, ⁴Radiology, Case Western Reserve University, Cleveland, OH, United States

Dystrophin, a component of the dystrophin-glycoprotein complex, plays a role in the formation and function of the blood-brain barrier (BBB). The absence of dystrophin has been shown to lead to a leaky BBB and enhanced arteriogenesis in vitro. To elucidate the function of dystrophin in maintaining water balance and perfusion at the BBB in vivo, we characterized the effect of dystrophin disruption on cerebral perfusion and water exchange across BBB using arterial spin labeling and diffusion-weighted MRI in dystrophin-deficient mice versus wild-type. Our results demonstrate a reduction in diffusion and increase in perfusion associated with the absence of dystrophin.

Yichao Yu¹, Gavin Kenny¹, Lin Zhang², N. M. Powell^1,3, H. Bobby Gaspar⁴, and Mark F. Lythgoe^1
1Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom, ²Shanghai Institute of Hematology, Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³Centre for Medical Image Computing, Department of Medical Physics and Bioengineering, University College London, London, United Kingdom, ⁴Centre of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, London, United Kingdom

Adenosine deaminase (ADA) deficiency is a major cause of severe combined immunodeficiency. Patients suffer from a loss of immune protection and a consequent susceptibility to infections, but also exhibit behavioural impairments and volume loss in certain brain structures. We have a mouse model of ADA deficiency, and using high resolution ex vivo MRI and tensor-based morphometry, we for the first time identified in the ADA deficient mice volumetric changes of brain structures that emerged later during development, mirrored human findings, but were much more extensive. This provides further evidence of brain abnormalities in this disorder and opens up new questions.

Keigo Hikishima^1,2, Kiyoshi Ando¹, Ryutaro Yano³, Yuji Komaki^1,2, Kenji Kawai¹, Takashi Inoue¹, Masayuki Yamada⁴, Toshio Itoh¹, Suketaka Momoshima⁵, Hirotaka James Okano⁶, and Hideyuki Okano^2
1Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan, ²Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan, ³Faculty of Health Sciences, Tokyo Metropolitan University, Tokyo, Japan, ⁴School of Health Science, Fujita Health University, Aichi, Japan, ⁵Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan, ⁶Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan

Movement dysfunction in Parkinson�fs disease is caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. We used a microscopic diffusion tensor tractography (DTT) technique with an isotropic resolution of 60 ƒÊm and three-dimensional histological analysis to visualize the nigrostriatal pathway in the common marmoset, a small non-human primate. We also developed longitudinal voxel-based analysis to detect the distribution of degeneration. In this study, we report that microscopic DTT visualized the nigrostriatal pathway and longitudinal voxel-based analysis assessed neuronal degeneration in a monkey model of Parkinson�fs disease.

Nellie Byun^1,2, Robert L Barry³, Richard Baheza², Stephen Damon⁴, John C Gore², and P Jeffrey Conn^1
1Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, United States, ²Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ³Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashviille, TN, United States, ⁴Neurology, Vanderbilt University Medical Center, Nashville, TN, United States

We performed functional connectivity and permutation analyses on two pharmacological MRI (phMRI) data sets to identify statistically significant differences between circuit correlations observed in (1) the amphetamine response versus (2) modulation of the amphetamine response by VU0360172 a compound that targets the metabotropic glutamate receptor subtype 5, a target for the treatment of schizophrenia. Correlation analysis of the phMRI responses, a translational approach for characterizing drug-related functional connectivity patterns, provided more information than traditional individual ROI amplitude results, revealing modulation of circuits connected to entorhinal, cingulate, and motor cortices, and striatum.

Giovanna Diletta Ielacqua¹, Felix Schlegel¹, Markus Rudin², and Jan Klohs^1
1Institute for Biomedical Engineering, ETH, Zurich, Zurich, Switzerland, ²Institute for Biomedical Engineering, Institute of Pharmacology and Toxicology, Zurich, Switzerland

It has been shown that in Alzheimer’s Disease amyloid deposition in cerebral microvessels plays an important role in cerebral perfusion. In this MRI study we investigated capillary density through relaxation rate shift index Q, and perfusion with bolus tracking . All measurements were performed on a 9.4T scanner equipped with a cryogenic phased-array coil, recording a 2D Spin Echo-RARE, a 3D Gradient Echo-FLASH and an EPI sequence. Our results show there is a decrease of capillary density and cortical perfusion in 24months-old arcAâ mice, suggesting that the index Q is a reliable indicator of capillary density in brain microvasculopathies

Marija M. Petrinovic^1,2, Michael Saxe¹, Barbara Biemans¹, Peter Scheiffele², Markus von Kienlin¹, and Basil Künnecke^1
1F. Hoffmann-La Roche Ltd, Pharma Research & Early Development, DTA Neuroscience, Basel, Basel, Switzerland, ²Biocenter, University of Basel, Basel, Basel, Switzerland

Alterations in neural function and neurochemistry have been proposed as mechanisms underlying behavioural deficits associated with autism spectrum disorder (ASD). We have leveraged fMRI/MRS in five mouse models of ASD to bridge the gap between genetic/molecular findings and behavioural phenotypes. fMRI revealed prominent neurofunctional alterations in brain regions implicated in socio-emotional, cognitive and sensorimotor processing. fMRI fingerprints were heterogeneous across the models, yet, they reflect the complexity of ASD symptoms found in patients. 1H-MRS in these models showed consistent changes in cerebral glutamate levels indicative of a dysbalance in excitatory/inhibitory neurotransmission which has been purported as a substrate for ASD.

Ling Guo¹, Xuan Vinh To¹, Xin Hong¹, Reshmi Rajendran¹, Si Kang Lew¹, Yee Ling Tan¹, Yihui Huang², Michael R. Hayden^2,3, Mahmoud A. Pouladi^2,3, and Kai-Hsiang Chuang^1
1Singapore BioImaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore, ²Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore, Singapore, ³Department of Medicine, National University of Singapore, Singapore, Singapore

Longitudinal structural MRI was conducted to track morphological changes in presymptomatic YAC128 Huntington disease (HD) mice. YAC128 mice, relative to wild-type, showed progressive atrophy of the striatum and white matter tracts starting from 1.5 months, while cortical atrophy was found only at 6 months. The progressive atrophy in striatum at very early age indicates the vulnerable areas. The neurodegeneration pattern identified will be useful for evaluation of preclinical treatment trials of HD.

Yael Piontkewitz¹, Yaniv Assaf¹, and Ina Weiner^1
1Tel-Aviv University, Tel-Aviv, Israel

Schizophrenia involves progressive structural brain aberrations preceding the onset of symptoms. This raises the question whether schizophrenia can be prevented. We used an animal model to assess the efficacy of the atypical antipsychotic clozapine to prevent the neuroanatomical deterioration. Pregnant dams were injected with the viral mimic Poly-I:C. Offspring received preventive treatment with clozapine during adolescence. At adulthood rats were scanned using the 7T scanner (Bruker). The protocol included quantitative T2 mapping and DTI. Poly-I:C led to the emergence of hallmark structural abnormalities associated with schizophrenia. Some of these structural abnormalities were non-existent following peri-adolescence administration of clozapine.

Sunil Koundal¹, Sonia Gandhi¹, Tanzeer Kaur², Rajendra P Tripathi¹, and Subash Khushu^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Timarpur, Delhi, India, ²Department of Biophysics, Panjab University, Chandigarh, India

Neurometabolic alterations in response to chronic high altitude stress were studied with 1H-MR Spectroscopy. Inositol and choline concentrations were significantly decreased after 7 and 14 days of altitude exposure which was linked to altered astrocyte metabolism and neuronal rescue effort respectively. A significant decrease in Glutamate+Glutamine after 14 day hypoxia reflected altered glutamate metabolism. An increment in taurine reflects protective effect from excitotoxic injury. There was no significant NAA change, implying retained neuronal integrity. This study along with in vitro High resolution NMR spectroscopy and other biochemical analysis may provide better insights of the injury and possible interventions.

Sunil Koundal¹, Sonia Gandhi¹, Tanzeer Kaur², Richa Trivedi¹, Rajendra P Tripathi¹, and Subash Khushu^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Timarpur, Delhi, India, ²Department of Biophysics, Panjab University, Chandigarh, India

Effect of high altitude exposure on water diffusion in brain hippocampus region was studied with the help of Diffusion Weighted Imaging by calculating Apparent Diffusion Coefficient (ADC) values from the region of interest. It was found that high altitude hypoxic stress had an effect on water diffusion properties in hippocampal region. There was significant decrease in ADC values after 14 days of high altitude stress in CA2/3 and Dentate gyrus (Dg) region of hippocampus while CA1 showed significant decrease after 21 days of stress. Decrease in ADC value depicted cytotoxic edema indicating changes in tissue architecture at micro structural level.

Bianca Gonzales Cerqueira¹, Shiliang Huang¹, Glenn M. Toney², and Timothy Q. Duong^1
1Research Imaging Institute, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Physiology, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, United States

This study evaluated the effects of chronic intermittent hypoxia (CIH) on basal CBF and stimulus-evoked responses in animals exposed to 14 and 28 days of CIH. We found that BOLD and CBF activations in response to forepaw stimulation trended toward a reduction with increasing CIH exposure duration, although did not reach statistical significance. Basal CBF in the somatosensory cortex decreased with increasing CIH exposure, significantly when controls were compared to 28 day CIH animals. There were no changes in cerebral rate of oxygen consumption, M value, or CBF response to hypercapnia among the groups.

Bianca Gonzales Cerqueira¹, Shiliang Huang¹, Glenn M. Toney², and Timothy Q. Duong^1
1Research Imaging Institute, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Physiology, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Sleep apnea is correlated with cardiovascular disease and cognitive deficits. Exposure to chronic intermittent hypoxia (CIH) is used to model sleep apnea. Rats underwent CIH for 14 or 28 days. CIH reduced basal CBF for all ROIs, significantly in the somatosensory cortex for 28-day CIH. CIH did not affect ADC or CBF response to oxygen challenge and hypercapnia. FA values decreased significantly in the somatosensory cortex and thalamus. We have demonstrated the use of MRI to evaluate structural and vascular changes in animals exposed to CIH consistent with results found in patients with sleep apnea.

Martin Herbert Schaffhauser^1,2, Dominik Maria Reisinger^1,2, Joel Marx¹, Michael Porambo¹, Jiangyang Zhang³, Michael V Johnston¹, and Seyed Ali Fatemi^1,2
1Neuroscience, Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United States, ²Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Despite the preventable nature of bilirubin encephalopathy, cases continue to occur and remain a significant problem in newborns. The Gunn rat is a rat model, featuring an enzyme deficiency resembling Crigler Najjar syndrome. Sulfadimethoxine was used to exaggerate bilirubin encephalopathy, leading to a dystonic phenotype. We evaluated the model in the chronic phase ex vivo through acquiring high-resolution images of T2-weighted sequences as well as DTI. While there were no FA changes, we show decreased cerebellar volumes in all mutant rats as well as decreased GP, ICP and MCP volumes in the dystonic animals.

Ulysse Gimenez¹, Fanny Cavarec², Antoine Depaulis², Hana Lahrech¹, and Colin Deransart^2
1CEA-Clinatec, Grenoble, France, ²Grenoble Institute of Neurosciences, La Tronche, France

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a well-validated model of absence epilepsy, and dopamine has been shown to play a modulatory role on absence seizures. The fasciculus retroflexus (FR) is a white matter tract involved in the release of dopamine. A microscopic 3D-Diffusion Tensor Imaging sequence was developed on 7T Bruker MRI and applied ex vivo on GAERS and Non Epileptic Control (NEC) rats. DTI fiber-tracking showed a decrease in the number of fibers detected in the FR, suggesting a contribution of this tract in the modified dopaminergic tone observed in epileptic rats.

Xiao-Qi Ding¹, Martin Meier², Marion Bankstahl³, Xiangyu Tang^1,4, Wolfgang Löscher³, Heinrich Lanfermann¹, and Jens P. Bankstahl^5
1Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Lower Saxony, Germany, ²Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Lower Saxony, Germany, ³Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Lower Saxony, Germany, ⁴Department of Radiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China, ⁵Preclinical Molecular Imaging, Department of Nuclear Medicine, Hannover Medical School, Hannover, Lower Saxony, Germany

Status epilepticus (SE) is a common insult that may lead to development of temporal lobe epilepsy characterized by hippocampal neurodegeneration, which is associated with psychological and cognitive dysfunctions. The present work investigated SE-induced neurodegeneration and behavioral dysfunction as well as possible neuroprotective treatment in rat by long term MRI follow-up study combined with a behavioral test battery. The results showed that SE-induced neurodegeneration is a long lasting process associated with behavioral changes that can be reduced by add-on treatment with phenobarbital.

Balasrinivasa R Sajja¹, Aditya N Bade², Biyun Zhou³, Mariano G Uberti¹, Santhi Gorantla², Larisa Y Poluektova², Michael D Boska^1,2, Howard E Gendelman², and Yutong Liu^1,2
1Radiology, University of Nebraska Medical Center, Omaha, Nebraska, United States, ²Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States, ³Anesthesiology, Tongji Medical College, Huanzhong University of Science and Technology, Wuhan, China

Longitudinal morphological phenotyping of HIV-1 mouse model can provide an assessment of brain structural changes during disease progression and therapeutic responses. An in vivo MEMRI based NSG mouse brain atlas was generated to assess volumetric effects on brain structures from the process of generating humanized mice. Our results determined significant size reduction in humanized mice brain structures. This procedure will be extended to track structure-wise changes during progression of HIV-1 infection in NSG human cell transplanted mice.

Raman Saggu¹, Emilie Pecchi¹, Guillaume Duhamel¹, Dorothée Faille², Frédéric Frassineti³, Laurent Daniel³, Georges Grau⁴, Monique Bernard¹, Patrick J Cozzone¹, and Angele VIOLA^1
1Aix-Marseille Université-CRMBM UMR CNRS 7339, Marseille, France, ²Laboratoire d'Hématologie et d'Immunologie Biologiques - U698, Paris, France, ³Service d’Anatomie Pathologique, Hôpital la Timone, Marseille, France, ⁴The University of Sydney, Camperdown, Australia

Cerebral malaria (CM) is the most lethal complication in the course of Plasmodium infection. Our purpose was to decipher the mechanisms by which EPO ameliorates CM in mice. We used an approach combining MRI techniques at high field (conventional MRI, perfusion MRI with the pCASL technique and angiography) for in vivo cerebral studies, with immunological and histological techniques. Our results show that administration of EPO prevents brain edema in responding animals, which is the cause of death in sham-treated CM mice. Our results demonstrate that EPO enhance brain perfusion via both short-term non-erythropoietic effects of EPO, and long-term erythropoietic effects.

Saurav B Chandra¹, Eric R Muir¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, United States

Dorzolamide (DZ) is clinically used to treat glaucoma by reducing intraocular pressure. However, its effect on blood flow is unknown. The goal of this study is to investigate the effect of topical DZ application on retinal and choroidal blood flow in DBA/2J mice, an established mouse model of glaucoma. Results are compared with C57BL/6J mice, used as a control group. This study indicates increased blood flow in the choroid of both DBA/2J as well as C57BL/6J mice models following topical application of Dorzolamide.

Nyoman D. Kurniawan¹, Andrew Janke¹, Mario F. Wullimann², David C. Reutens¹, and Jeremy F.P. Ullmann^1
1Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, Australia, ²Department Biologie II - Neurobiologie, Ludwig Maximilians-University, Planegg-Martinsried, Germany

We describe ex-vivo high spatial resolution adult zebrafish brain model at 7 micron resolution and super-resolution short-track track density map at 5 micron resolution from MRI data acquired at 16.4T.

Shir Hofstetter¹ and Yaniv Assaf^2
1Sagol School Of Neuroscience, Tel Aviv University, Tel Aviv, Israel, Israel, ²Sagol School Of Neuroscience, Tel Aviv University, Israel, Israel

DTI is a valuable method in exploring structural plasticity. Studies found changes following short tasks of only hours, but the initial temporal and spatial progression of this process is unknown. In the current study we used the Morris water maze paradigm to explore the evolution of plasticity in the hippocampus of adult rats at different stages of the learning process. Rats were scanned following diverse number of trials in the maze. Results show that the extent of change the tissue undergoes during the learning process is dynamic. Additionally, circular order of the spatial progression of these changes was found.