Mechanisms of Neural Degeneration & Damage 1

Wednesday 3 June 2015

Swati Rane¹, Manus J Donahue^2,3, and Daniel Claassen^3
1Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ³Neurology, Vanderbilt University, Nashville, TN, United States

We assessed the relation of CSF-α-synuclein levels with connectivity of frontal brain regions involved in executive function. All frontal brain regions showed inverse relation with CSF-α-synuclein concentrations while the posterior regions showed a positive correlation with CSF-α-synuclein concentrations.

Jessica Steventon¹, Rebecca Trueman², Anne E Rosser³, and Derek K Jones^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²University of Nottingham, England, United Kingdom, ³School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom

Widespread atrophy occurs in Huntington’s disease (HD) and cerebrospinal fluid (CSF) fills the remaining space, which can lead to an increased CSF-based partial volume artefact in diffusion MRI studies. In this work, we use the tissue volume fraction (TVF) which is a metric of the signal from tissue after eliminating the partial volume component. We compared the relative sensitivity of TVF and diffusion tensor indices in predicting disease burden in HD and find that TVF is more sensitive to a genetic marker of disease severity and to reported functional capacity, and should be adopted as a microstructural metric.

Xueling Suo¹, Du Lei¹, Fuqin Chen¹, Lei Li¹, Nannan Li², Lan Cheng², Rong Peng², and Qiyong Gong^1
1Huaxi MR Research Center (HMRRC), Department of Radiolody, West China Hospital, Chengdu, Sichuan, China, ²Department of Neurology, West China Hospital, Chengdu, Sichuan, China

Parkinson's disease (PD) is a progressive neurodegenerative disease. Previous resting-state fMRI studies of PD have primarily focused on ROI methods. Recently there have been emerging studies employing graph theoretical approaches to investigate the structural and functional brain connectome of PD patients. However, little is known as to the topological characteristics of functional connectome of early-stage PD. Our study aimed to investigate topological Properties of the functional connectome in early-stage PD patients with mild cognitive impairment by graph theoretical analysis

Yujuan Zhao¹, Noah Snyder¹, Tiejun Zhao², Liza Bruk¹, James Eles¹, Xia Li¹, X. Tracy Cui¹, and Tamer S. Ibrahim^1
1University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Siemens Medical Solutions USA, Pittsburgh, Pennsylvania, United States

Neurodegenerative diseases are generally not well-understood with no effective drugs available to treat and prevent these diseases. A potent antioxidant compound could be incorporated in magnetic nanoparticles (MNPs) and delivered into central nervous systems (CNS) tissue for lowering oxidative stress related to numerous neurodegenerative diseases. In this study, the feasibility of using MRI fields to trigger the drug loaded MNPs is investigated. In-vitro and in-vivo results are provided and In-vivo drug release from silica magnetic nanoparticles via MRI stimulation was demonstrated by observing fluorescein release from silica magnetic nanoparticles injected into the brain of rodents.

Lei Li¹, Du Lei², Xueling Suo², Xinyu Hu², Jiechuan Ren³, Xiaoqi Huang², and Qiyong Gong^2
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, ²Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Sichuan, China, ³Department of Neurology, West China Hospital of Sichuan University, Sichuan, China

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by sudden attack of choreoathetosis or dystonia. The basal ganglia-thalamo-cortical motor circuits is proposed as the pathophysiological basis of the PKD disease. The purpose of this study is to detect the topological organization of whole-brain networks in PKD using graph theoretical approaches. The result showed PKD patients exhibited a much more active global and local connectivity characterized by higher local specialization and global integration than controls. Especially, the patients exhibited enhanced nodal centralities in the basal ganglia, supporting the idea that PKD is sequence of basal ganglia dysfunction.

Jason Langley¹, Daniel E Huddleston², Nishant Zachariah³, Xiangchuan Chen¹, and Xiaoping Hu^1
1Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States, ²Center for Health Research, Southeast, Kaiser Permanente, Atlanta, GA, United States, ³Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Degeneration of the substantia nigra (SN) is a hallmark of many neurodegenerative disorders including Parkinson’s disease and visualization and volumetric quantification of the SN would be beneficial to early detection of PD. Magnetization transfer contrast (MTC) imaging is sensitive to neuromelanin-containing structures in the brain quantitative susceptibility mapping (QSM) is sensitive to iron. This abstract compares the segmentation results and signal characteristics of the SN from MTC images and QSM maps. We found neuromelanin and iron sensitive regions are spatially incongruent and have different signal characteristics.

Malek I Makki¹ and Jeremy J Laukka^2
1MRI Research, University Children Hospital of Zurich, Zurich, Switzerland, ²Department of Neuroscience and Neurology, University of Toledo, Toledo, Ohio, United States

Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder of the central nervous system, caused by mutations affecting proteolipid protein 1 (PLP1) the major protein in myelin. Twelve PMD patients were examined with DTI. Mutation was characterized as null mutation (N=3), moderate (N=5) and severe (N=4). We selected three levels along the cortico-spinal tract: posterior-limb of the internal capsule, pons and cerebral peduncle. In the pons we observed significantly higher radial diffusion both in severe compared to null (p=0.002) and in severe compared to moderate mutation (p=0.015). We observed higher axial diffusion in the posterior-limb in severe compared to null mutation (p=0.008).

An Vo¹, Wataru Sako¹, Frank M Skidmore², David Eidelberg¹, and Aziz M Ulug^1,3
1Center for Neurosciences, Feinstein Institute for Medical Research, Manhasset, New York, United States, ²Neurology, University of Alabama, Alabama, United States, ³Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey

The purpose of this study is using rsfMRI to determine affected brain networks in PD. rsfMRI were analyzed using spatial group independent component analysis. Thirteen ICs representing independent contributions from cerebellum, thalamus, SMA, and from premotor/prefrontal and parietal cortex, superior frontal gyrus achieved maximum between-group separation. PD pattern was obtained by a linear combination of these thirteen components using estimated parameters of linear regression model. Subject scores representing the mean expression of the PD-related pattern were abnormally elevated in the PD patients and the RBD as well. A trend toward reduced network expression with treatment was seen and a significant correlation was observed between the levodopa-mediated changes in PDRP expression and baseline measurements of network activity in this dataset.

Hao Hu¹, Vincent Chin-Hung Chen², Ming-Chou Ho³, Yeu-Sheng Tyan^4,5, and Jun-Cheng Weng^4,5
1Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China, ²Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan, ³Department of Psychology, Chung Shan Medical University, Taichung, Taiwan, ⁴School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ⁵Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Previously disrupted topological organization of major depressive disorder (MDD) patients regarding functional brain network has been declared by several studies. However, only few studies mentioned about the particular structural brain network changes of this patient group. Diffusion tensor imaging (DTI) enables comprehensive whole brain mapping of the white matter tracts that link regions throughout the entire brain. Thus, our study aims to map the structural connectomic changes over MDDs based on DTI tractography using graph theory and network-based statistic analyses. In the result, meaningfully altered topological organization of structural connectivity network was found.

Vincent Magnotta¹, Casey Johnson¹, John Wemmie², Shafik Wassef¹, Hans Johnson³, Jeffrey Long², and Jane Paulsen^2
1Radiology, University of Iowa, Iowa City, IA, United States, ²Psychiatry, University of Iowa, Iowa City, IA, United States, ³Electrical and Computer Engineering, University of Iowa, Iowa City, IA, United States

Multiple quantitative relaxation parameters (T1ρ, T2, and T2*) were used to study progression in premanifest Huntington’s Disease. T1ρ showed the greatest change in the striatum and was significantly associated with with disease progression. These changes were also independent of T2 changes suggesting that the changes were likely due to changes in chemical exchange. T2* changes were observed in the globus pallidus but these were not associated with disease progression. The changes in T1ρ are consistent with a decrease in glucose concentrations or pH.

Sniya Valsa Sudhakar¹ and Maya Mary Thomas^2
1Radiodiagnosis, Christian Medical College, Vellore, Tamil Nadu, India, ²Neurology, cmc vellroe, Vellore, Tamil Nadu, India

This is a pictorial assay of the varied MR manifestations of SSPE based on a retrospective study of 90 cases The authors have emphasised on the fact that SSPE can mimick a wide spectrum of diseases on MR and awareness would help in instituiting early diagnosis and supportive tratment thus improving patietns qaulity of life

Byeong-Yeul Lee¹, James R. Connor², Wei Chen¹, and Qing X. Yang^2,3
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Department of Neurosurgery, The Pennsylvania State University College of Medicine, Hershey, PA, United States, ³Center for NMR Research, Department of Radiology, The Pennsylvania State University College of Medicine, Hershey, PA, United States

Restless legs syndrome (RLS) is a neurological disorder characterized by extremely uncomfortable senstations in the limbs. Due to the explicit presence of the sensory and pain symptoms in patients with RLS, we investigated the cortical thickness in the sensory-motor and the central pain system using advanced surface classification method. Compared to controls, both vertex-wise and ROI-based analysis revealed that RLS exhibits a significantly reduced cortical thickness in the postcentral cortex and increased cortical thickness in the cingulate cortex bilaterally. These findings of involvement of the sensory and the pain system in RLS gain new insights for better understanding of the pathophysiology underlying RLS, and the abnormal cortical thickness in these brain regions could provide a useful surrogate marker for studying RLS and diagnosis.

Xiao-Ling Yang^1,2, Leon C. Ho^1,3, Yolandi van der Merwe^1,4, Ian P. Conner^2,4, Seong-Gi Kim^1,5, Gadi Wollstein², Joel S. Schuman^2,4, and Kevin C. Chan^1,2
1NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ³Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China, ⁴Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea

This study determined spatiotemporally the progression of intraocular pressure, ocular morphology and microstructural integrity of the visual pathways in transgenic DBA/2J mice and age-matched C57BL/6J mice using high-resolution anatomical MRI and diffusion tensor MRI at 9.4 Tesla in order to better understand the etiology and pathophysiological events during glaucoma progression . Our data showed that the ocular dimensions and microstructures of visual pathway in D2 began to change at the onset of IOP increase at 8-9 months old, which progressed further at 12 months old, resulting in significant deterioration in visuomotor function compared to B6 mice of the same age. In addition, caution should be taken when using C57BL/6J mice as an age-matched negative given the slight but significant increase in IOP and compromised microstructural integrity at older ages.

Hyug-Gi Kim¹, Dan-Bi Kim², Jang-Hoon Oh¹, Soon Chan Park², Hak Young Rhee³, Chang-Woo Ryu², Won-Chul Shin³, Dal-Mo Yang², and Geon-Ho Jahng^2
1Biomedical Engineering, Kyung Hee University, YoungIn, Gyeonggi-do, Korea, ²Radiology, Kyung Hee University Hospital-Gangdong, Seoul, Korea, ³Neurology, Kyung Hee University Hospital-Gangdong, Seoul, Korea

To estimate the neuronal activations during an associative working memory task in patients with cognitive normal (CN), mild cognitive impairment (MCI) and Alzheimer¡¯s diseases (AD), BOLD and ASL fMRI were studied. The fMRI data during a face–name association encoding task were obtained from 25 CN, 19 MCI, and 23 AD subjects with a block design and with three conditions (novel, un-novel, and fixation). The differences of BOLD and ASL fMRI among the three groups were investigated. We found ASL fMRI was useful to estimate the significant difference of neuronal activations for three groups compared to BOLD fMRI.

Won-Jin Moon¹, Ju Yeon Park², Jin Woo Choi², Yeon Sil Moon³, Seol-Heui Han³, Ki-Chang Kwak⁴, and Jong-Min Lee^4
1Department of Radiology, Konkuk University School of Medicine, Seoul, Seoul, Korea, ²Konkuk University School of Medicine, Seoul, Korea, ³Department of Neurology, Konkuk University School of Medicine, Seoul, Korea, ⁴Department of Biomedical Engineering, Hanyang University, Seoul, Korea

Volumetric measurement of T1 hyperintense substantia nigra can be a useful imaging marker for evaluating neuromelanin loss in neurodegenerative diseases including AD and PDD.

Enrico De Vita^1,2, Marie-Claire Porter^3,4, Ivor Simpson⁵, Zoe Fox⁶, Gerard Ridgway⁷, Sebastien Ourselin⁵, Peter Rudge^3,4, Diana Caine^3,4, Rolf Jager^1,2, Tarek Yousry^1,2, John Collinge^3,4, Simon Mead^3,4, Harpreet Hyare^3,4, and John S Thornton^1,2
1Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, ²Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, ³MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom, ⁴National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, United Kingdom, ⁵Centre for Medical Image Computing, University College London, London, United Kingdom, ⁶Education unit, UCL Institute of Neurology, London, United Kingdom, ⁷Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom

At 1.5T Magnetisation Transfer (MTR) correlated with clinical severity in inherited prion patients and was shown to be potentially more sensitive to structural changes than conventional imaging. We exploited the higher SNR available at 3T to further elucidate associations between regional cerebral MTR and disease progression in prion disease patients scanned serially (including sporadic, iatrogenic, variant forms alongside inherited). At baseline patients displayed lower MTR values in several ROIs vs controls; MTR correlated with clinical assessment (evaluated using the prion MRC score). MTR also decreased longitudinally and the rate of decrease correlated with rate of decrease of MRC score.

Arzu Ceylan HAS¹, Irsel TEZER², Serap SAYGI², and Kader K. OGUZ^1,3
1National Magnetic Resonance Research Center (UMRAM), Ankara, Ankara, Turkey, ²Department of Neurology, Hacettepe University, Ankara, Turkey,³Department of Radiology, Hacettepe University, Ankara, Turkey

Medial Temporal Lobe Epilepsy, Hippocampal Sclerosis, Default Mode Network, Functional Connectivity, Resting State, Morphometry.

Paula Trujillo^1,2, Paul Summers¹, Luca Mainardi², Sergio Cerutti², Seth A Smith^3,4, Alex K Smith^3,4, 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, ³Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States,⁴Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

In Neuromelanin-sensitive MRI, magnetization transfer (MT) prepulses improve the observable contrast of neuromelanin (NM) containing structures (i.e. Substantia Nigra (SN) and Locus Coeruleus (LC)) relative to surrounding tissues. The purpose of the study was to assess the effect of the MT pulses by examining the z-spectra of the SN and its surrounding tissues in turbo-spin echo (TSE) and gradient echo images. Maximal MT effect was seen for MT pulses at an offset of 835 and 1525 Hz for TSE and gradient echo sequences respectively.

Sung-han Lin¹, Chin-Song Lu², Yi-Hsin Weng², Yao-Liang Chen³, Yi-Ming Wu³, and Jiun-Jie Wang^1
1Medical Imaging and Radiological Science, Chang Gung University, Taoyuan County, Taiwan, Taiwan, ²Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan, ³Department of Radiology and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan

The Parkinson’s disease (PD) has been associated with iron deposition in the basal ganglia and striatum.The Quantitative Susceptibility Mapping (QSM) was applied for measurement of the susceptibility differences between PD patients and normal controls. We investigated the PD affected regions including the caudate nucleus, the red nucleus, the globus pallidus, the putamen, and the substantia nigra. We found that the regions with significant increased susceptibility were consistent with the PD pathology and suggested that the feasibility of QSM as a sensitive method for the measurement of the severity of the pathological changes underlying PD

Bo Hou¹, Ke Zheng², Hui You¹, Jing Yuan³, Hai-yun Wang², Xue-mei Li², and Feng Feng^1
1Department of Radiology, Peking Union Medical College Hospital, Beijing, Beijing, China, ²Department of Nephrology, Peking Union Medical College Hospital, Beijing, China, ³Department of Neurology, Peking Union Medical College Hospital, Beijing, China

Cognitive impairment is common in individuals with chronic kidney disease (CKD), while relative studies are not so abundant as other degenerative diseases. With VBM and voxel-based analysis of CBF generated with ASL, this study compared GM, WM and CBF changes between CKD patients with and without cognitive impairment, and revealed some significant brain changes in cognition impaired patients treated with long term hemodialysis.

Yi-Ming Wu¹, Chin-Song Lu², Yi-Hsin Weng², Yao-Liang Chen¹, Sung-han Lin³, and Jiun-Jie Wang^3
1Department of Radiology and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ²Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan, ³Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan

To evaluate the capability of resting state functional MRI in indentifying the disease-specific changes in functional brain networks from PD patients with or without impulse control disorders (ICD).PD patients showed significantly enhanced striatal functional connectivity with sensori-motor cortex.Compared with healthy subjects and PD patients without ICD, PD patients with ICD also showed significantly increased striatal connectivity with the ACC and prefrontal cortex, which are involved in execution and reward system.This study shows that mapping striatal functional connectivity is feasible and may aid in understanding the pathophysiology of PD and ICD.

Darrell Ting Hung Li¹, Edward Sai Kam Hui¹, Queenie Chan², Siew-eng Chua³, Grainne McAlonan^3,4, Shu Leong Ho⁵, and Henry Ka Fung Mak^1
1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, ²Philips Healthcare, Hong Kong, China, ³Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ⁴Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King’s College London, London, United Kingdom, ⁵Department of Medicine, The University of Hong Kong, Hong Kong

Degeneration of dopaminergic neuron is one of the major clinical characteristics of Parkinson’s disease (PD). Abnormal iron deposition in the mid-brain nuclei was postulated to be the cause of neurodegeneration. In this study, we employed quantitative susceptibility mapping (QSM) as a tool to examine iron content of different brain nuclei. Iron concentrations in terms of magnetic susceptibility of the 6 brain nuclei were presented. ROI analysis revealed high iron concentration in substantia nigra of PD patients which confirmed the clinical findings. This study also demonstrated QSM as a potential tool for evaluation of in vivo iron metabolism in neurodegenerative disease.

Ying Xiong¹, Zhipeng Xu², Qiang Zhang³, Shiqi Yang¹, Shun Zhang¹, and Wenzhen Zhu^1
1Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, ²Pathophysiology Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, ³Neurology department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

This study aims to investigate the possible alterations in spontaneous neural activity through resting-state functional MRI (rs-fMRI) in type 2 diabetes mellitus (T2DM) related cognitive impairment. Thirty-four T2DM patients were divided into two groups based on their cognition status. The intrinsic and spontaneous neural activity, represented by the regional homogeneity (ReHo), was detected to decrease in right temporal regions and to increase in bilateral frontal regions. Weaker connectivities of multiple brain regions were also revealed in the cognitive impairment group. These multi-functional brain disorders revealed by rs-fMRI may help to discover the susceptible regions to T2DM induced cognitive dysfunction.

Zhenchao Tang¹, Zhenyu Liu², Jiaojiao Liu³, Hongjun Li³, Enqing Dong¹, and Jie Tian^2
1School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai, Shandong Province, China, ²Institute of Automation, Chinese Academy of Sciences, Beijing, China, ³Beijing YouAn Hospital, Capital Medical University, Beijing, China

Simian immunodeficiency virus (SIV) infection causes Fractional Anisotropy (FA) alterations, which represent white matter integrity degeneration. In our longitudinal study, we used Tract Based Spatial Statistic (TBSS) to access white matter integrity degeneration with the advance of disease. We find that SIV impairs macaque white matter integrity in the inferior temporal regions selectively, and may cause damage to the ventral visual pathway. The results are consistent with previous studies on HIV affected patients. We also find that Lower FA values were correlated with higher CD4+/CD8+ ratio. Our MRI findings indicate that FA may be a potential marker for monitoring the disease progression.

Mechanisms of Neural Degeneration & Damage 2

Wednesday 3 June 2015

Gerd Melkus^1,2, Santanu Chakraborty^1,2, and Pierre Bourque^3
1Department of Medical Imaging, The Ottawa Hospital, Ottawa, ON, Canada, ²Department of Radiology, University of Ottawa, Ottawa, ON, Canada, ³Department of Neurology, University of Ottawa, Ottawa, ON, Canada

There is no definite technique for demonstrating UMN involvement in ALS/PLS and UMN findings on clinical examination may not be evident until late in the disease course. T2 hypointensity in the motor cortex in ALS has been described before and can be assessed better due to increased resolution of SWI. QSM processing and analysis of the motor cortex and control area enables quantification of these signal changes. In our series there is a significant correlation between QSM values and presence of UMN signs (spasticity). However, larger prospective studies will be needed to determine diagnostic and prognostic value of this sign.

Jaivijay Ramu¹, Tetyana Konak¹, Merle G Paule¹, Joseph Hanig², and Serguei Liachenko^1
1Neurotoxicology, NCTR / FDA, Jefferson, AR, United States, ²OTR, CDER / FDA, White Oak, MD, United States

Diffusion Tensor Imaging was used to characterize the life cycle of the hexachlorophene (HC) induced neurotoxicity in the rat brain. Axial and radial diffusivity as well as ADC has dramatically increased after the start of HC treatment, reaching its peak at day 6 and reversing back to normal at day 20, while FA did not change significantly. These changes suggest about transient changes in myelinated brain tissue of the rat, consistent with edema.

Arzu Ceylan HAS¹, Ozlem CELEBI², Andac UZDOGAN³, Filiz AKBIYIK³, Bulent ELIBOL², Esen SAKA², and Kader K. OGUZ^1,4
1National Magnetic Resonance Research Center (UMRAM), Ankara, Ankara, Turkey, ²Department of Neurology, Hacettepe University, Ankara, Turkey, ³Department of Biochemistry, Hacettepe University, Ankara, Turkey, ⁴Department of Radiology, Hacettepe University, Ankara, Turkey

Parkinson's Disease, Cognitive Functioning, Resting State, Default Mode Network, Functional Connectivity, Diffusion Tensor Imaging, Tract Based Spatial Statistics.

Douglas G Peters^1,2, Carson J Purnell¹, Jian-Li Wang³, Paul J Eslinger⁴, Megha Vasavada³, Fatima Ali-Rahmani¹, Qing X Yang³, James R Connor¹, and Mark David Meadowcroft^1,3
1Neurosurgery, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ²Neural and Behavioral Sciences, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ³Radiology, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ⁴Neurology, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States

A voxel-based statistical parametric analysis of R₂ transverse relaxation in cognitively normal H63D-HFE human and H67D knock-in mice compared to control patients and mice was accomplished. Widespread decreases in relaxation were found in white association fibers throughout the brain of H63D patients and in white matter tracks of the H67D mice. The R₂ changes observed in both the human-H63D and mouse-H67D data suggest that the sequential process of myelinogenesis is refashioned, resulting in modified myelin membrane proton compartmentalization in patients with HFE mutations.

Fariborz Mahmoudi^1,2, Mohammad-Reza Nazem-Zadeh¹, Jason M. Schwalb³, Ellen L. Air³, Hassan Bagher-Ebadian¹, Manpreet Kaur³, Rushna Ali³, Saeed Shokri¹, Kost V. Elisevich⁴, and Hamid Soltanian-Zadeh^1,5
1Departments of Radiology, Research Administration, Henry Ford Health System, Detroit, Michigan, United States, ²Computer and It Engineering Faculty, Islamic Azad University, Qazvin Branch, Qazvin, Qazvin, Iran, ³Departments of Neurosurgery, Henry Ford Health System, Detroit, Michigan, United States, ⁴Department of Clinical Neurosciences, Spectrum Health System, Grand Rapids, Michigan, United States, ⁵CIPCE, School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran

Mesial temporal lobe epilepsy (mTLE) is the most common type of refractory focal epilepsy. Concordant electroencephalographic, neuropsychological and Magnetic Resonance Imaging (MRI) findings often lateralize the epileptogenic side permitting surgical resection of the mesial temporal structures, without further investigation. In cases of unclear lateralization, implantation of intracranial electrodes for long term monitoring (Phase II) is needed to localize the epileptogenic zone. Unfortunately, Phase II monitoring may lead to infection, intracranial hemorrhage, and elevated intracranial pressure. In this study, we have developed, a combinational model based on imaging and other diagnostic procedures to try to reduce the need for Phase II monitoring. Briefly the purpose of this study is, developing a model that would not only enhance patient safety, but also would reduce economic burden.

Xiangchuan Chen¹, Daniel Huddleston^1,2, Jason Langley¹, and Xiaoping Hu^1
1Emory University, Atlanta, Georgia, United States, ²Kaiser Permanente Center for Health Research Southeast, Atlanta, Georgia, United States

Alterations in the caudal portion of substantia nigra (SN) in Parkinson’s disease (PD) were investigated through magnetic resonance imaging (MRI) of a PD and a control groups. By measuring the volumes of SN in different slice locations, we found that the PD patients had smaller SN than the controls in the caudal portion of SN. The distance between the centers of mass of the left and right SNs was also shorter in the PD than in the controls in the same locations. These results are consistent with the findings of histological studies on post mortem brains.

Štefan Holiga^1,2, Robert Jech³, Karsten Mueller¹, Dušan Urgošík⁴, Matthias L. Schroeter^1,2, and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Clinic for Cognitive Neurology & Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany, ³Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Czech Republic, ⁴Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague, Czech Republic

Early stages of Parkinson’s disease (PD) are associated with the pathology occurring in the lower brainstem and gradually progressing towards the neocortex. PD is already in later stages when the pathology targets the substantia nigra and motor symptoms become apparent. Here, we found a correspondence between the ascending gradient of PD-pathology and functional connectivity patterns of the resting-state-(rs)-fMRI in the brainstem. Rs-fMRI of the brainstem should be therefore considered as a potential non-invasive marker of the disease’s early phases. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

Chenchen Liu¹, Nuri B Farber², Joel R Garbow³, and Joseph JH Ackerman^4
1Chemistry, Washington University in St.Louis, St. Louis, MO, United States, ²Psychiatry, Washington University in St.Louis, St. Louis, MO, United States,³Radiology, Washington University in St.Louis, St. Louis, MO, United States, ⁴Chemistry and Radiology, Washington University in St.Louis, St. Louis, MO, United States

Apoptosis is a cell-eliminating process in which unhealthy/unneeded cells are culled in a controlled manner. Currently, histology is the gold-standard method for qualifying/quantifying apoptosis. However, histological techniques require resection and destruction of the tissue, thus longitudinal pre-clinical and clinical studies are infeasible. MRI may offer a non-invasive/non-destructive and translatable means to detect and quantify apoptosis. We have initiated such studies by taking advantage of the high sensitivity afforded by pre-clinical MRI at 11.74 T with a rodent ethanol-induced apoptosis model. We observed a 23% signal enhancement in apoptotic cingulate cortex with T1-weighted imaging 4h after ethanol injection.

Serguei Liachenko¹, Jaivijay Ramu¹, Tetyana Konak¹, Merle Paule¹, and Joseph Hanig^2
1Neurotoxicology, NCTR / FDA, Jefferson, AR, United States, ²OTR, CDER / FDA, White Oak, MD, United States

T₂ mapping was used to detect the neurotoxicity in the rat brain caused by acute kainic acid administration. The T₂ changes were quantified using three methods: 1) simple threshold; 2) statistical parametric mapping; and 3) difference with the own baseline. It was shown that method #3 has the most sensitivity towards the detection of the neurotoxic changes of the rat brain.

Chunmei Li¹, Xuna Zhao², Haibo Chen¹, Jinyuan Zhou³, and Min Chen^1
1Beijing Hospital, Beijing, Beijing, China, ²Peking University, Beijing, China, ³Johns Hopkins University, Maryland, United States

This present study is to compare the diagnostic efficiency of CEST imaging and DTI in PD. Our results clearly show that the non-invasive CEST MRI methodology is able to generate unique image contrasts that are based on the changes in cytoplasmic proteins and peptides, as well as the neuronal loss in several specific brain regions in PD patients. For DTI, no significant differences were found for the mean diffusivity (MD) in the five regions between PD patients and normal controls. Decreased fractional anisotropy (FA) was observed only in the substantia nigra in PD patients. Therefore, we got the conclusion that multiple CEST imaging signals could potentially serve as imaging biomarkers to aid in the non-invasive molecular diagnosis of PD and it may apply more information than DTI.

Xiaoling Zhang¹, Bundy Wong², Min Tang¹, Sipan Chen¹, Defeng Wang², and Jian Yang^3
1Department of Radiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China, ²Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, New Territories, Hong Kong, ³Department of Radiology, Xi'an Jiao Tong University, Xi'an, Shaanxi, China

The aim of this study was to assess the volumes of white matter lesions (WMLs) of T2DM on MRI using an automatic quantification method, and to explore the relationship of T2DM and WMLs, and some characteristic change of WMLs in T2DM. 26 patients with T2DM and 28 healthy persons underwent MRI including T1WI and FLAIR sequences. The total volume of WMLs in T2DM group, especially volumes of WMLs in bilateral frontal lobes and parietal lobe assessed by an automatic measurement method were significantly larger than those in control group, and HbA1c, Systolic and Diastolic BP were correlated with the WMLs volume in frontal and bilateral parietal lobe in the T2DM group, which maybe associate with the cognitive dysfunction.

Massimo Filippi¹, Federica Agosta¹, Lidia Sarro¹, Aleksandra Tomic², Sebastiano Galantucci¹, Paola Valsasina¹, Marina Svetel², Alessandro Sodero¹, Nikola Kresojevic², Giancarlo Comi³, and Vladimir S. Kostic^2
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Yugoslavia, ³Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Structural MRI changes were assessed in 19 Writer’s Cramp (WC) primary dystonia patients and 30 healthy controls, analyzing both gray and white matter differences. WC patients showed a diffuse pattern of cortical volume and area increase, as well as a diffuse pattern of WM damage involving both sensorimotor and extra-sensorimotor regions. These findings suggest a complex network dysfunction playing a role in the development of focal hand dystonia. Structural and DT MRI hold promise to achieve a better in vivo understanding of such an enigmatic disease.

Heather L Gray-Edwards¹, Nouha Salbi^2,3, Ashley N Randle¹, Judith Hudson⁴, Ronald Beyers⁵, Miguel Sena Esteves⁶, Thomas Denney^5,7, and Douglas Martin^1,8
1Scott-Ritchey Research Center, Auburn Univeristy, Auburn, Al, United States, ²Seimens Healthcare, Malvern, PA, United States, ³Auburn Univeristy MRI Research Center, Auburn Univeristy, AL, United States, ⁴Clinical Sciences, Auburn Univeristy, AL, United States, ⁵Auburn University MRI Research Center, Auburn Univeristy, AL, United States, ⁶Neurology, University of Massachusetts, MA, United States, ⁷Department of Electrical Engineering, Auburn Univeristy, AL, United States, ⁸Anatomy, Phsiology and Pharmacology, Auburn Univeristy, AL, United States

GM1 gangliosidosis is a fatal neurodegenerative disease of children for which there is no cure. A well characterized feline GM1 model was used to test intracranial gene therapy. Gene therapy resulted in a 5 fold increase in lifespan and marked attenuation of neurologic signs. MRI and Single voxel MR spectroscopy was performed in the thalamus, centrum ovale, parietal cortex, temporal lobe, occipital cortex and cerebellum. AAV gene therapy partially normalized MRI and metabolite alterations in the GM1 cat brain, and data suggest that MRS is a sensitive measure of therapeutic efficacy in discrete brain areas.

Yue Xing¹, Stefan Schwarz¹, Nin Bajaj², Penny Gowland³, and Dorothee Auer^1
1Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Division of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, Nottinghamshire, United Kingdom, ³Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

To assess whether gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD), we used multivariate pattern classification analysis (MVPA) on cortical thickness in people with Parkinson’s. Our result show MVPA is sensitive to discriminate the patterns of GM loss of these two subtypes, which suggest GM atrophy may provide useful information for classification different motor subgroup of PD.

Sarah Al-Bachari¹, Hedley Emsley², Rishma Vidyasagar^1,3, and Laura Parkes^4
1Imaging, University of Manchester, Manchester, United Kingdom, ²Neurology, Royal Preston Hospital, Preston, Lancashire, United Kingdom, ³Department of Anatomy and Neurosciences, University of Melbourne,Victoria, Victoria, 3010, Australia, ⁴Imaging, Manchester University, Manchester, United Kingdom

Idiopathic Parkinson’s disease (IPD) is the second most common neurodegenerative disorder; vascular mechanisms are rapidly emerging as key players in the neurodegenerative process in preclinical studies, yet clinical studies remain equivocal. To investigate the neurovascular status in IPD we used arterial spin labelling (ASL) MRI techniques measuring cerebral blood flow (CBF) and arterial arrival time (AAT), comparing findings to patients with known cerebrovascular disease (CVD) and healthy controls. Results revealed a diffuse widespread increase in AAT in the IPD group compared to controls, which was similar to, but more pronounced than the prolongation of AAT seen in CVD, providing evidence of an alteration in neurovascular status.

Andre Ticlo¹, Sofia Reimão², Hugo Alexandre Ferreira¹, João Marcos Sousa¹, Daisy Abreu³, Joaquim Ferreira³, Jorge Campos², and Rita Gouveia Nunes^1
1Instituto de Biofisica e Engenharia Biomedica, Faculdade de Ciencias, Universidade de Lisboa, Lisbon, Portugal, ²Neurological Imaging Department of Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal, ³Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal

Fractional Anisotropy (FA) and Mean Diffusivity (MD) have been shown to be affected in Parkinson’s Disease (PD) but no prior studies have investigated how these metrics change over time. Recently, there has also been much interest in applying graph theory to characterize brain connectivity. We imaged a group of PD patients and a control group over a period of 1 year. Changes in FA, MD and connectivity metrics were investigated after evaluating the reproducibility of the methodology. FA, MD and global efficiency were shown to be promising biomarkers to evaluate structural changes with disease progression in PD patients.

Karsten Mueller¹, Sandrine Bisenius¹, Adrian Danek², Janine Diehl-Schmid³, Klaus Fassbender⁴, Hans Foerstl³, Armin Giese², Holger Jahn⁵, Frank Jessen⁶, Jan Kassubek⁷, Johannes Kornhuber⁸, Bernhard Landwehrmeyer⁷, Martin Lauer⁹, Albert Ludolph⁷, Markus Otto⁷, Johannes Prudlo¹⁰, Anja Schneider¹¹, Katharina Stuke¹, and Matthias L Schroeter^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Clinic of Neurology and Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich, Germany, ³Clinic and Polyclinic for Psychiatry and Psychotherapy, Technical University of Munich, Germany, ⁴Clinic and Polyclinic for Neurology, Saarland University Homburg, Germany, ⁵Clinic for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany, ⁶Clinic and Polyclinic for Psychiatry and Psychotherapy, University of Bonn, Germany, ⁷Clinic and Polyclinic for Neurology, University of Ulm, Germany, ⁸Clinic for Psychiatry and Psychotherapy, University of Erlangen, Germany, ⁹Clinic and Polyclinic for Psychiatry, Psychosomatic Medicine, and Psychotherapy, University of Wuerzburg, Germany, ¹⁰Clinic and Polyclinic for Neurology, University of Rostock, Germany, ¹¹Clinic for Psychiatry and Psychotherapy, University of Goettingen, Germany

We investigated structural brain differences between patients with progressive supranuclear palsy (PSP) and healthy controls with T1-weighted images acquired in five different centers of the German consortium for fronto-lobar degeneration (FTLD). Using voxel-based morphometry, we found a major decline in gray matter density in brainstem and thalamus, but also in striatum (putamen and caudate) that is in-line with the current literature. SVM classification provides a high sensitivity of disease detection when using relevant brain regions in feature selection.

Yangsoo Ryu¹, Yoonho Nam¹, Han Jang¹, Sung Suk Oh², Eung Yeop Kim³, and Jongho Lee^1
1Department of Electrical and Computer Engineering, Seoul National University, Seoul, Seoul, Korea, ²Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea, ³Gachon University Gil Medical Center, Radiology, Incheon, Korea

In this work, we proposed an approach to enhance the CNR of the nigrosome 1 structure. Additionally, a navigator echo was acquired to compensate for physiological noises (respiration) in the data. The new approach substantially improved CNR and successfully visualized nigrosome 1 at 3T.

Florian Borsodi¹, Christian Langkammer², Valeriu Culea¹, Lukas Pirpamer¹, Stefan Quasthoff¹, Christian Enzinger^1,3, Reinhold Schmidt¹, Franz Fazekas¹, and Stefan Ropele^1
1Dept. of Neurology, Medical University of Graz, Graz, Austria, ²MGH/HST Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, United States, ³Div. of Neuroradiology, Dept. of Radiology, Medical University of Graz, Graz, Austria

Previous studies showed microstructual tissue changes in the corticospinal tract (CST) of patients suffering from amyotrophic lateral sclerosis (ALS), but were conflicting in their findings and their relation to clinical function. In our study, we investigated diffusion properties and magnetization transfer in the CST and other major white matter tracts of 33 ALS patients and 35 age-matched healthy controls, and how they relate to disease duration and disability. We found subtle but diffuse microstructural tissue changes in the CST only, which caused a regional increase in the radial diffusivity and a decrease of the magnetization transfer ratio, but were unrelated to clinical findings.

Frank C.G. van Bussel¹, Walter H. Backes¹, Paul A.M. Hofman¹, Alfons G.H. Kessels², Tamar M. van Veenendaal¹, Harm J. van de Haar¹, Martin P.J. van Boxtel³, Miranda T. Schram⁴, Coen D.A. Stehouwer⁴, Joachim E. Wildberger¹, and Jacobus F.A. Jansen^1
1Radiology, Maastricht University Medical Center, Maastricht, Limburg, Netherlands, ²Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, Limburg, Netherlands, ³Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, Limburg, Netherlands, ⁴Internal Medicine, Maastricht University Medical Center, Maastricht, Limburg, Netherlands

Type 2 Diabetes Mellitus (T2DM) is associated with cognitive decline. A prominently affected cognitive domain is memory, for which the hippocampus is essential. Diffusion MRI enables assessment of hippocampal microstructure through the fractional anisotropy, mean diffusivity, and tractographic connectivity. This study showed that T2DM participants have less hippocampal connectivity to the frontal lobe. In addition, impaired memory performance correlated with the altered hippocampal connectivity to the temporal and parietal lobes.

Mickael Ehrminger¹, Alice Latimier², Daniel Garcia-Lorenzo³, Smaranda Leu-Semenescu⁴, Marie Vidailhet⁵, Isabelle Arnulf⁴, and Stephane Lehericy^6
1Ecole Normale Superieure, Paris, France, ²Service des pathologies du sommeil, ICM - Institut du Cerveau et de la Moelle, Paris, France, ³CENIR - Centre for NeuroImaging Research, ICM - Institut du Cerveau et de la Moelle, Paris, France, ⁴Service des pathologies du sommeil, Hopital Pitie-Salpetriere, Paris, France,⁵Service de Neurologie, ICM - Institut du Cerveau et de la Moelle, Paris, France, ⁶CENIR - Center for NeuroImaging Research, ICM - Institut du Cerveau et de la Moelle, Paris, France

Rapid eye movement (REM) sleep behavior disorders (RBD) are symptoms of nocturnal violence that occur in isolation in patients with idiopathic RBD (iRBD) and are considered a premotor sign of parkinsonism. We show reduced signal intensity in the locus coeruleus/subcoeruleus complex (LCSC) using neuromelanin-sensitive MRI in iRBD that correlated with the percentage of atonia during REM sleep. These results suggest that the LCSC complex is involved in the pathophysiology of iRBD.

Naying He¹, Fuhua Yan², Huawei Ling², Yong Zhang³, and Zhongping Zhang^4
1Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China, ²Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³MR Research, GE Healthcare, China, Shanghai, China, ⁴MR Research, GE Healthcare, China, Guangzhou, China

A reliable in vivo quantitative evaluation of iron deposition is important, especially in early PD. Several technical problems prevent the conventional GRE approaches from quantitatively detect local susceptibility changes which are assumed to reflect iron depositions in brain regions. In this work, we utilized a novel post-processing method, quantitative susceptibility mapping (QSM) to investigate the iron deposition changes in early PD, and explore their relationships with clinical futures. The results indicate that QSM is useful for quantitatively detection of iron alteration in brain, which might be an early event in the progression of PD.

Linlin Cong¹, Eric R. Muir¹, Yusheng Qian², Cang Chen², Senlin Li², and Timothy Q. Duong^1
1Research Imaging Institute, University of Texas Healthy Science Center at San Antonio, san antonio, Texas, United States, ²Departments of Medicine and Pharmacology, University of Texas Healthy Science Center at San Antonio, san antonio, Texas, United States

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is characterized by a number of motor symptoms. MitoPark transgenic mouse is a relatively new model of PD that exhibits several critical clinical features of PD, including progressive neurodegeneration and death of dopamine neurons, followed by motor dysfunction. This study investigated CBF, ADC and T2* in the caudate putamen and substantia nigra of MitoPark mice. MitoPark mice showed trends of reduced ADC and CBF, and significantly reduced T2* value compared to controls. These results were corroborated with behavioral deficits in loco-motor activity and histological loss of dopamine neurons.

Sandy Goncalves^1,2, Todd K Stevens², Robert Bartha^1,2, and Neil Duggal^1,3
1Medical Biophysics, Western University, London, Ontario, Canada, ²Centre for Functional and Metabolic Mapping, Robarts Research Institute - Western University, London, Ontario, Canada, ³Clinical Neurological Sciences, University Hospital - London Health Sciences Centre, London, Ontario, Canada

Surgical outcome for patients suffering from cervical spondylotic myelopathy (CSM) is unpredictable with varying motor and sensory symptom recovery. We show that absolute NAA levels are lower in CSM patients compared to controls in motor and sensory cortex and that following spinal decompression surgery absolute NAA levels decrease in a similar temporal pattern but in the opposite direction as clinical motor and sensory function. This finding suggests that low NAA levels may be a benefit for functional recovery although the neural mechanisms involved have not been elucidated.

Alzheimer's Disease

Wednesday 3 June 2015

Rui Wang¹, Saying Li¹, Min Chen¹, Jinyuan Zhou², Dantao Peng³, Chen Zhang¹, and Yongming Dai^4
1Department of Radiology, Beijing Hospital, Beijing, Beijing, China, ²Johns Hopkins University School of Medicine, Maryland, United States, ³Department of Neurology, China-Japan Friendship Hospital, Beijing, Beijing, China, ⁴Philips Healthcare, Shanghai, China

Our aim is to evaluate the feasibility of Amide proton transfer (APT) imaging to detect cerebral abnormality in Alzheimer¡¯s disease (AD) patients. Twenty AD patients and 20 normal controls were enrolled for APT imaging. The magnetic resonance ratio asymmetry (MTRasym) at 3.5ppm of bilateral hippocampi, temporal white matter regions, occipital white matter regions and cerebral peduncles were measured. We found that MTRasym(3.5ppm) of bilateral hippocampi were increased in AD patients than normal controls. MTRasym(3.5ppm) of bilateral hippocampi were negatively correlated with MMSE. Our results suggested that APT imaging could potentially provide imaging biomarkers for the non-invasive molecular diagnosis of AD.

Tabassum Majid^1,2, Deric Griffin^1,2, Zachary Criss II¹, Asante Hatcher³, Matthew Jarpe⁴, and Robia Pautler^2,5
1Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, United States, ²Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, United States, ³Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States, ⁴Acetylon Pharmaceuticals, Boston, MA, United States, ⁵Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States

The development of HDAC-6 inhibitors for Alzheimer's disease (AD) therapy has been met with limited success due to lack of selectivity and brain bioavailibility. In this study, we demonstrate the effectiveness of a novel, selective HDAC-6 inhibitor (ACY-738) treatment in the APP/PS1 mouse model of AD. We demonstrate improvements in axonal transport (MEMRI), learning and memory assays, post-translational protein modifications of the microtubule, and amyloid pathology. We believe this pre-clinical proof of concept study contributes to recent evidence of specific, selective HDAC-6 inhibitor therapies in neurodegenerative diseases.

Gang Chen¹, Hao Shu^1,2, Guangyu Chen¹, Wenjun Li³, Zhan Xu¹, Zan Wang², Duan Liu², B. Douglas Ward¹, Jennifer Jones⁴, Malgorzata Franczak⁴, Joseph Goveas³, Piero Antuono⁴, Zhijun Zhang², and Shi-Jiang Li^1
1Biophysics, Medical College of Wisconsin, milwaukee, WI, United States, ²Neurology, Affiliated ZhongDa Hospital of Southeast University, China, ³Psychiatry, Medical College of Wisconsin, milwaukee, WI, United States, ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

The RfMRI data were collected through an international collaboration effort across 17 imaging sites. The imaging biomarkers for mild cognitive impairment (MCI) were obtained from 217 subjects (110 cognitively normal (CN) and 107 MCI). To test whether the biomarkers can be applied to the prospective studies, another set of RfMRI data were obtained from 217 disjoint subjects. The results showed that the RfMRI biomarkers were validated on the prospective data set (p<0.004). The RfMRI biomarkers were found to be robust, reliable and can be applied to prospective studies.

Vanda Viola¹, Laura Serra¹, Elisa Tuzzi¹, Chiara Mastropasqua¹, Barbara Spanò¹, Barbara Basile¹, Mario Torso¹, Giovanni Giulietti¹, Elena Makovac¹, Camillo Marra², Mara Cercignani³, Carlo Caltagirone^4,5, and Marco Bozzali^1
1Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Roma, RM, Italy, ²Institute of Neurology, Università Cattolica, Rome, Italy, ³Clinical Imaging Science Centre, Brighton and Sussex Medical School, Brighton, United Kingdom, ⁴Departmente of Clinical and Behavioral Neurology, Santa Lucia Foundation IRCCS, Rome, Italy, ⁵Department of Neuroscience, Università "Tor Vergata", Rome, Italy

Clinical Symptoms can often overlap between Alzheimer Disease (AD) and Dementia with Lewy Body (DLB), and this can cause delayed or incorrect diagnosis. The aim of the present investigation was to detect dissimilarities between AD and DLB’s structural and functional connectivity. Specifically, structural connectivity was analyzed in the inferior frontal occipital fasciculus and in the superior cingulum bundle using diffusion tractography, while functional connectivity was explored in the left and right fronto-parietal networks during resting state. Our results highlighted that structural and functional connectivity were altered in both hemispheres in AD and only in the right hemisphere in DLB patients.

Ying Xiong^1,2, Yi Sui², Zhipeng Xu³, Shiqi Yang¹, Kejia Cai^2,4, Wenzhen Zhu¹, and Xiaohong Joe Zhou^2,4
1Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, ²Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States, ³Pathophysiology Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, ⁴Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

This study aims at studying the white matter alterations in type 2 diabetes mellitus (T2DM) patients and the relationship with cognitive impairment using DTI. Forty two T2DM patients were divided into two groups based on their cognition status, and imaged along with healthy controls. It was found that the white matter changes were associated more closely to cognition than to diabetes. Compromised myelin sheath may explain changes in DTI parameters observed in T2DM patients with cognitive impairment. It was also observed that there was no difference in FA and MD between the diabetes patients with normal cognition and the controls.

Eva Manzanedo Sáenz¹, Alexandra Cristobal Huerta¹, Elena Molina Molina¹, Ana Beatriz Solana², Virginia Mato¹, Daniel García Frank¹, Eva Alfayate³, Juan Álvarez-Linera⁴, and Juan Antonio Hernández-Tamames^1
1Universidad Rey Juan Carlos, Móstoles, Madrid, Spain, ²General Electric, Munich, Germany, ³Fundación Reina Sofía - Fundación CIEN, Madrid, Madrid, Spain,⁴Hospital Rúber Internacional, Madrid, Madrid, Spain

Default mode network functional connectivity differences between amnestic Mild Cognitive Impairment (aMCI) patients before and after being diagnosed and their differences with healthy controls (HC) were analyzed in this work. Two sessions per subject, separated in time 399±22 days, were included in the analysis. Our findings corroborate that DMN functional connectivity impairment and compensation effects coexist in aMCI compared to HC. Moreover, the compensation effect is significant at least one year before aMCI diagnosis and covers larger areas. Therefore DMN rsfMRI connectivity alterations could be useful for early detection of aMCI or even of Alzheimer’s Disease.

Sinan Zhao¹, Archana Venkataraman², Peipeng Liang^3,4, and Gopikrishna Deshpande^1,5
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn university, Auburn, AL, United States, ²Department of Diagnostic Radiology, School of Medicine, Yale University, New Haven, CT, United States, ³Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China, ⁴Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Key Laboratory for Neurodegenerative Diseases, Ministry of Education, Beijing, China, ⁵Department of Psychology, Auburn University, Auburn, AL, United States

Connectivity analysis of resting state fMRI has been widely used to identify biomarkers of Alzheimer’s disease (AD) based on brain network alterations. However, it is difficult to interpret these connectivity results because traditionally, our knowledge of brain function is anchored on regions and not connections. Therefore, a method was recently introduced for identification of disease foci based on non-directional functional connectivity differences between populations. Here we extend this concept for identifying focal directional connectivity deficits in AD as compared to matched controls. We found such a focus in the brain stem whose output was significantly diminished in AD

Leonardo A Rivera-Rivera¹, Patrick Turski², Eric M Schrauben¹, Phillip Kilgas¹, Carson Hoffman¹, Kevin M Johnson¹, Michael Loecher¹, Chuck Illingworth², Sterling C Johnson², and Oliver Wieben^1,3
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Medicine, University of Wisconsin-Madison, WI, United States, ³Radiology, University of Wisconsin-Madison, WI, United States

Cerebral arteries are often morphologically altered and dysfunctional in Alzheimer’s disease. In this study, 4D flow MRI was used to measure intra-cranial flow features, particularly mean flow and pulsatility index in patients with AD, MCI and in healthy controls. We found a statistically significant decrease in mean flow, and an increase in pulsatility index for the AD and MCI. With the large volume coverage and high temporal and spatial resolution, 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.

Matteo Figini¹, Alessandro Scotti¹, Ileana Zucca¹, Emanuela Maderna², Margherita Ruggerone², Marcella Catania², Giuseppe Di Fede², Fabio Moda², Fabrizio Tagliavini², and Maria Grazia Bruzzone^3
1Scientific Direction, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Milan, Italy, ²Neuropathology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy, ³Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy

In this work, the potential of diffusion MRI (dMRI) parameters in the characterization of neuropathological features of Alzheimer’s diseases was investigated in a mouse model. Transgenic mice treated with different doses of a synthetic peptide were submitted to 7T dMRI at different time points. A reduction of mean diffusivity was associated with the deposition of amyloid plaques highlighted by immunohistochemistry. If this preliminary result will be confirmed in further works, mean diffusivity may be an in vivo biomarker of the amount of amyloid plaques, with applications in the diagnosis and monitoring of therapy effects on Alzheimer’s patients.

Jiri M.G. van Bergen¹, Xu Li², Michael Wyss³, Simon J. Schreiner¹, Stefanie C. Steininger¹, Jun Hua², Roger Nitsch¹, Klaas P. Pruessmann³, Peter C.M. van Zijl², Marilyn S. Albert⁴, Christoph Hock¹, and Paul G. Unschuld^1
1Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Zurich, Switzerland, ²F.M. Kirby center for Functional Brain Imaging, Kennedy Krieger Institute and Johns Hopkins School of Medicine, Baltimore, Maryland, United States, ³Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland, ⁴Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States

In this study it was shown that subjects with Mild Cognitive Impairment (MCI) do not have significantly different susceptibility values in the basal ganglia and the major cortical areas. Moreover, susceptibility values do not show strong correlations with structure volumes. Susceptibility in gray matter has been shown to relate to tissue iron content, which is known to be elevated in advanced stages of Alzheimer’s disease (AD). However, in these subjects with increased risk for late onset AD, our results suggest that susceptibility as a single measure cannot be used as a biomarker for brain dysfunction as reflected by cognitive impairment.

Rachelle Crescenzi^1,2, Catherine DeBrosse^3,4, Ravi Prakash Reddy Nanga⁴, Kevin D'Aquilla⁵, Guruprasad Krishnamoorthy⁴, Leonard Nettey⁴, Hari Nath⁴, Hari Hariharan⁴, John A. Detre⁶, Virginia M.-Y. Lee⁷, and Ravinder Reddy^4
1Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Pennsylvania, Philadelphia, PA, United States, ³Biochemistry and Molecular Biophysics, University of Pennsylvania, PA, United States, ⁴Radiology, University of Pennsylvania, PA, United States,⁵University of Pennsylvania, PA, United States, ⁶Neurology, University of Pennsylvania, PA, United States, ⁷Pathology and Laboratory Medicine, University of Pennsylvania, PA, United States

Trial

Sinan Zhao¹, CK Dharmendra Kumar², D Narayana Dutt², Peipeng Liang^3,4, and Gopikrishna Deshpande^1,5
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Department of Medical Electronics, Dayananda Sagar College of Engineering, Bangalore, India, ³Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China, ⁴Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Key Laboratory for Neurodegenerative Diseases, Ministry of Education, Beijing, China,⁵Department of Psychology, Auburn University, Auburn, AL, United States

We estimated Betweenness Centrality (BC) from directed networks derived from the application of Granger causality to resting state fMRI data acquired from: Normal Control (NC), Early MCI (EMCI), Late MCI (LMCI) and Alzheimer’s disease (AD). We used an additional metric called middlemen power (MP) which not only characterizes information flow through a node as in BC, but also estimates the power of the node in terms of its criticality for information flow in the entire network. We found that BC and MP of a few brain regions progressively decreased from NC to EMCI to LMCI to AD.

Santosh K. Yadav¹, Anup Singh^2,3, Arshi Rizwan⁴, Christos Davatzikos⁵, Elias R. Melhem⁶, Deepak Kaura¹, Ena Wang¹, Francesco M. Marincola¹, and Mohammad Haris^1,2
1Research Branch, Sidra Medical and Research Center, Doha, Qatar, ²Radiology, Center for Magnetic Resonance and Optical Imaging, University of Pennsylvania, Philadelphia, PA, United States, ³Center for Biomedical Engineering, Indian Institute of Technology, New Delhi, India, ⁴All India Institute of Medical sciences, New Delhi, India, ⁵Section of Biomedical Image Analysis, University of Pennsylvania, Philadelphia, PA, United States, ⁶Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, MD, United States

In the current study, we have measured the gender based changes in the T1ρ relaxation time in medial-temporal-lobe and hippocampus in brain of Parkinson's disease (PD) patients. Larger changes in T1ρ relaxation in female PD patients were observed compared to male PD patients. This change in T1ρ might be attributed to the physiological and genomic differences between male and female, and may provide a clinical measure to differentiate the severity of disease and outcome of the treatment responses among gender.

Santosh K. Yadav¹, Anup Singh^2,3, Arshi Rizwan⁴, Christos Davatzikos⁵, Elias R. Melhem⁶, Deepak Kaura¹, Ena Wang¹, Francesco M. Marincola¹, and Mohammad Haris^1,2
1Research Branch, Sidra Medical and Research Center, Doha, Qatar, ²Radiology, Center for Magnetic Resonance and Optical Imaging, University of Pennsylvania, Philadelphia, PA, United States, ³Center for Biomedical Engineering, Indian institute of Technology, New Delhi, India, ⁴All India Institute of Medical sciences, New Delhi, India, ⁵Section of Biomedical Image Analysis, University of Pennsylvania, Philadelphia, PA, United States, ⁶Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, MD, United States

ApoE ε4 allele has been identified as a major risk factor for Alzheimer’s disease (AD). In the current study, reduced cortical thickness in various brain's regions was observed in mild cognitive (MCI) impairment and Alzheimer’s disease (AD), when compared with controls. MCI and AD with ApoE ε4 carriers showed greater reduction in cortical thicknesses than non-carriers. The pathological mechanisms contributing to reduced cortical thicknesses likely include loss of neurons and other supporting cells.

Mark David Meadowcroft^1,2, Douglas G Peters^1,3, Carson J Purnell¹, Jian-Li Wang², Paul J Eslinger⁴, Megha Vasavada², Qing X Yang², and James R Connor^1
1Neurosurgery, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ²Radiology, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ³Neural and Behavioral Sciences, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States, ⁴Neurology, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, United States

Iron accumulation in the brain and oxidative stress are observed in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). AD patients were stratified based on their HFE (H63D and C282Y) and transferrin (C2) gene carrier status and had statistical parametrics transverse relaxation analysis completed. AD patients who are carriers of H63D, C282Y, and/or C2 mutations exhibit a widespread increase in transverse relaxation within white matter association fibers across the brain. This pattern is indicative of white matter alterations in AD, congruent with the hypothesis and data showing that AD has an integral white matter component.

In-Young Choi^1,2, Jeffrey M. Burns³, Debra K. Sullivan⁴, Hung-Wen Yeh⁵, William M. Brooks^1,2, and Phil Lee^1,6
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Neurology, University of Kansas Medical Center, Kansas City, KS, United States, ³Neurology, University of Kansas Medical Center, Kansas City, Kansas, United States, ⁴Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, United States, ⁵Biostatistics, University of Kansas Medical Center, Kansas City, KS, United States, ⁶Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Increased generation of free radicals leads to oxidative damage and changes in antioxidant status and cognitive function. Thus, a reduction in glutathione (GSH), a major antioxidant, might be an early event in aging and neurodegeneration. In this study, we measured the relationship between cerebral GSH, nutrient intake and cognitive function in aging and AD using doubly-selective multiple quantum GSH CSI at 3T. The GSH levels were significantly lower in AD compared with age/sex-matched controls and young adults. We also found a positive correlation of GSH with dairy intake as well as cognitive function, suggesting the importance of an adequate antioxidant status.

Geon-Ho Jahng¹, Danbi Kim¹, Soonchan Park¹, Dong Kyun Lee², Jong-Min Lee², Hak Young Rhee³, Chang-Woo Ryu¹, Jang-Hoon Oh⁴, Hyug-Gi Kim⁴, and Dal-Mo Yang^1
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Seoul, Korea, ²Biomedical Engineering, Hanyang University, Seoul, Seoul, Korea, ³Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Seoul, Korea, ⁴Biomedical Engineering, Kyung Hee University, Suwon, Gyeonggi-do, Korea

To gray matter volume (GMV) loss with double inversion recovery (DIR) in patients with Alzheimer¡¯s disease (AD), we included 25 mild or probable AD, 25 amnestic mild cognitive impairment (MCI), and 25 elderly cognitive normal (CN) subjects. Both 3D DIR and 3D T1W images were acquired. GMV loss in the AD group compared with CN or MCI group was depicted in both DIR and 3DT1W images. However, DIR was much more sensitive to evaluate GMV loss compared to 3DT1W. With DIR, GMV loss in AD compared with CN and MCI was showed in the temporal and frontal areas.

Zhenhua Zhang¹, Zhongwei Chen¹, Haiwei Miu¹, and Qiong Ye^1
1The department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

Both Arterial Spin Labeling (ASL) and Intravoxel incoherent motion (IVIM) are capable of evaluating some aspect of perfusion information. Alzheimer¡¯s disease shows change in perfusion and anatomy. In this pilot study, we applied both ASL and IVIM to explore the characteristics features of perfusion in early stage of AD patients.

Weiwei Wang¹, Rui Hu¹, Ziheng Zhang², Qingwei Song¹, Ailian Liu¹, and Yanwei Miao^1
1Radiology Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China, ²GE Healthcare China, Beijing, China

Alzheimer's disease (AD) is the most common CNS degenerative disease in aged people and causes senile dementia1. Diffusion kurtosis imaging (DKI) is a method that can obtain the non-Gaussian diffusion of water. This work was to evaluate the application of DKI on white matter microstructure damage examination in AD, and it was found DKI can quantitatively evaluate the white matter changes in AD patients and the Dr values in the temporal WM can be as the best individual biomarkers of differentiation AD to controls. In addition, the changes of DKI parameters indicated the axonal loss and myelin damage of AD

Hyug-Gi Kim¹, Dan-Bi Kim², Jang-Hoon Oh¹, Hak Young Rhee³, Chang-Woo Ryu², Soon Chan Park², Dal-Mo Yang², Yi Wang^1,4, Tian Liu⁴, and Geon-Ho Jahng^2
1Biomedical Engineering, Kyung Hee University, YoungIn, Gyeonggi-do, Korea, ²Radiology, Kyung Hee University Hospital-Gangdong, Seoul, Korea, ³Neurology, Kyung Hee University Hospital-Gangdong, Seoul, Korea, ⁴Biomedical Engineering and Radiology, Cornell University, New York, New York, United States

To estimate the quantitative susceptibility effect on a number of echoes of gradient-echo sequences, two sequences were run in subjects with cognitive normal (CN), mild cognitive impairment (MCI) and Alzheimer¡¯s diseases (AD). Quantitative susceptibility mapping (QSM) was reconstructed with the single-echo (seQSM) and with multiple-echo (meQSM) data. QSM maps were compared among three groups. We found higher sensitivity of meQSM data than seQSM data. The meQSM technique has been proposed to accurately estimate the amounts of irons compared with seQSM technique. In addition, QSM was useful to investigate susceptibility effects in AD brain with the voxel-based analyses.

Tsung-Yuan Li¹, Ni-Jung Chang¹, Wei-Che Wu², Jyh-Wen Chai^1,3, and Clayton Chi-Chang Chen^1,4
1Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan, ²Department of Psyciatry, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan, ³College of Medicine, China Medical University, Taichung, Taiwan, Taiwan, ⁴Department of Biomedical Engineering, Hung Kuang University, Taichung, Taiwan, Taiwan

The changes of indices in diffusion tensor images (DTI) of patients with dementia are well-discussed in recent years. However, the comorbidity of dementia and depression was observed. In this study, we focused on the white matter changes associated with depressive symptoms in dementia and the relationship between DTI indices and cognitive functions in depressed and non-depressed patients. By an ROI-based analysis of the indices in DTI, we investigated the differences between patients of dementia with depression and without depression. Furthermore, we correlate the differences with the score of some clinical cognitive test to figure out the subtle differences.

Elisabeth Stühler^1
1Department of Computer and Information Science, University of Konstanz, Konstanz, Baden-Württemberg, Germany

New dementia-related features are presented to differentiate between various stages of Alzheimer’s disease. Prior registration of MRI-scans, possibly unsuccessful and always time-consuming, is avoided by employing local invariant features which are independent of image scale and orientation. Feature detectors are implemented based on scale-space theory in an automatized image processing workflow, and tested on a standardized MRI collection comprising 382 T1 MRI scans from patients with Alzheimer's Disease or mild cognitive impairment, and from a control group. The approach is not only very efficient for processing large datasets, but also first order statistics of features already differentiate significantly between classes.

Tabassum Majid^1,2, Caiwei Guo³, Tao Ma⁴, Erik Klann⁴, and Robia Pautler^1,2
1Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, United States, ²Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas, United States, ³Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States, ⁴New York University, New York, New York, United States

Antioxidant therapies for Alzheimer's disease (AD) have been met with limited success. Previous work from our lab has demonstrated that genetic superoxide dismutase 2 overexpression can ameliorate Alzheimer's pathology in the Tg2576 mouse model of AD. After establishing the role of superoxide in the pathogenesis of AD, we sought to explore the role of catalase overexpression in an aggressive AD model (APP/PS1). We report improvements in axonal transport rate as well as significant improvements in long-term potentiation within the hippocampus. From our findings, we add evidence to elucidate the role of specific redox species in AD.

Richard J. Dury¹, Latha Velayudhan², Penny A. Gowland¹, and Susan T. Francis^1
1Sir Peter Mansfield Imaging Centre, The University of Nottingham, Nottingham, United Kingdom, ²Department of Health Sciences, Leicester General Hospital, Leicester, United Kingdom

We investigate haemodynamic changes in Alzheimer’s Disease (AD) and how this relates to resting state network (RSN) activity. Using Arterial Spin Labelling at multiple post-label delay times we assess cerebral blood flow and tissue transit time changes in AD patients and an age-matched healthy control (HC) group. CBF is found to be reduced in AD compared to the HC group, with a trend for increased in TTT. In the default mode network (DMN) nodes of the inferior parietal lobe (IPL) a significant reduction in CBF is found. However, changes in CBF were not linked to altered network activity.

MS 1

Wednesday 3 June 2015

Thomas Tourdias^1,2, Vincent Planche¹, Bassem Hiba³, Aline Desmedt¹, Gerard Raffard³, Aude Panatier¹, Stéphane Oliet¹, and Vincent Dousset^1,2
1INSERM U862 Neurocentre Magendie, University of Bordeaux, Bordeaux, France, ²Department of Neuroradiology, Bordeaux University hospital, Bordeaux, France,³UMR CNRS 5536, University of Bordeaux, Bordeaux, France

Early memory impairment was demonstrated in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. High-resolution DTI showed a selective decrease of FA in the molecular layer (ML) of the dentate gyrus of the cognitively-impaired EAE-mice compared to controls. While there was diffuse hippocampal microglia activation, a selective dendritic loss and neuronal death in the ML of the dentate gyrus were the main correlate of the low FA in EAE-mice. Treatment with the microglia inhibitor minocycline protected against this neurodegenerative process and prevented memory impairment; the effect being measurable as an increase of FA in treated-mice compared to placebo.

Raveena Dhaliwal¹, Nabeela Nathoo¹, Ying Wu¹, James A. Rogers², V. Wee Yong², and Jeff F. Dunn^1
1Radiology, University of Calgary, Calgary, Alberta, Canada, ²Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

Susceptibility weighted MRI has been used to detect hypointensities in MS and animal models of MS. We showed that, in the experimental autoimmune encephalopathy (EAE) model of MS, many hypointensities were caused by deoxyhemoglobin. We hypothesized that this indicated hypoxia. To determine if hypoxia was present in spinal cords of EAE mice, we used MRI SWI at 9.4T to detect hypointensities and pimonidazole to detect hypoxia. Hypoxia and hypointensities were observed in day 7 and 20 EAE mice. Inflammation was seen at day 20. We concluded that tissue and venous hypoxia can occur prior to onset of symptoms in EAE.

Ian Tagge^1,2, Steven Kohama³, Jim Pollaro¹, Lawrence Sherman³, Dennis Bourdette⁴, Randy Woltjer⁴, Scott Wong³, and William Rooney^1,2
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, United States, ²Biomedical Engineering, Oregon Health & Science University, Portland, OR, United States, ³Oregon National Primate Research Center, Oregon Health & Science University, OR, United States, ⁴Neurology, Oregon Health & Science University, Portland, Oregon, United States

Inflammation, blood brain barrier (BBB) compromise, and vascular recruitment are common in neurodegenerative diseases. Gadolinium based contrast agents (GBCA) reveal BBB permeability. Blood pool contrast agents probe cerebral blood volume in-vivo. Japanese Macaque Encephalomyelitis (JME) is a spontaneous demyelinating disease similar to human multiple sclerosis. We use bolus injection of ferumoxytol (FeO) to investigate vascular expansion in acute JME. FeO accumulation indicates macrophage activity in and around acute lesions in JME. GBCA and FeO enhancements are colocalized, with the FeO volume generally exceeding that of GBCA. These findings suggest that vascular expansion extends well beyond the area of BBB compromise.

Caroline Guglielmetti¹, Jelle Veraart², Ella Roelant³, Zhenhua Mai⁴, Jasmijn Daans⁵, Johan Van Audekerke⁴, Jelle Praet⁴, Peter Ponsaerts⁵, jan Sijbers², Annemie Van der Linden⁴, and Marleen Verhoye^4
1Bio Imaging Lab, University of Antwerp, WILRIJK, ANTWERPEN, Belgium, ²IBBT Vision LaboratoryDepartment of Physics, University of Antwerp, ANTWERPEN, Belgium, ³StatUa Center for Statistics, University of Antwerp, ANTWERPEN, Belgium, ⁴Bio Imaging Lab, University of Antwerp, ANTWERPEN, Belgium,⁵Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, Vaccine and Infect, ANTWERPEN, Belgium

Sensitivity of diffusion kurtosis imaging (DKI) to detect microstructural alterations has been demonstrated in patients suffering from several neurological disorders. Despite advances in neuroimaging techniques, the majority of cortical alterations present in multiple sclerosis patients still fail to be detected. In this work, we used the well characterized cuprizone mouse model for brain demyelination and evaluated the sensitivity of in vivo DKI measurements for the non-invasive detection of cortical grey matter and white matter alterations. We showed that DKI can probe cortical demyelination and allow the detection of white matter inflammation and demyelination following cuprizone administration.

Olga Marshall¹, Sanjeev Chawla¹, Hanzhang Lu², Ilya Kister³, Jacqueline Smith¹, and Yulin Ge^1
1Radiology/Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States, ³Neurology, New York University School of Medicine, New York, NY, United States

The default mode network (DMN) is a well-established and critical network, which has been shown to be associated with healthy cognitive function and is known to be disrupted in various neurological conditions, including multiple sclerosis (MS). Cerebrovascular reactivity (CVR) is a measure of healthy neurovascular coupling and overall brain function. In this study, we quantify the CVR deficit seen within the DMN, in order to shed some light on the cognitive deficits that MS patients often experience.

Elizabeth Monohan¹, Wendy Vargas¹, Sneha Pandya², Michael Dayan², Thanh Nguyen², Ashish Raj², Sandra Hurtado³, and Susan Gauthier^1
1Neurology and Neuroscience, Weill Cornell Medical College, New York, NY, United States, ²Radiology, Weill Cornell Medical College, New York, NY, United States,³Public Health, Weill Cornell Medical College, New York, New York, United States

Our study utilized FAST-T2, a T2-relaxometry technique, to study myelin water fraction (MWF) within two types of early MS lesions: enhancing and new non-enhancing T2 lesions. Additionally, we exploited the T2 spectrum and utilized a novel approach to measure resolving edema within these lesions types. Enhancing lesions showed a greater and more variable change in MWF on follow up scan versus new non-enhancing lesions.

Nabeela Nathoo^1,2, Ying Wu¹, James A. Rogers^2,3, V. Wee Yong^2,3, and Jeff F. Dunn^1,4
1Radiology, University of Calgary, Calgary, Alberta, Canada, ²Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ³Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, ⁴Experimental Imaging Centre, University of Calgary, Calgary, Alberta, Canada

We showed previously that susceptibility weighted imaging (SWI) detects hypointensities due to intravascular deoxyhemoglobin in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) during peak motor dysfunction. In this study, we characterized the time course of SWI lesion load as a biomarker of reduced venous oxygenation over the EAE disease course. Two main observations emerged: 1) changes in venous oxygenation may precede the onset of motor dysfunction in EAE mice; and 2) maximum SWI lesion load occurred before or coincided with maximum motor dysfunction. SWI could be used to shed light on venous oxygenation in EAE and MS.

Irene Vavasour¹, Alex MacKay^1,2, David Li¹, Cornelia Laule^1,3, and Anthony Traboulsee^4
1Radiology, University of British Columbia, Vancouver, British Columbia, Canada, ²Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada, ³Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, ⁴Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Alemtuzumab is a multiple sclerosis (MS) therapy designed to inhibit inflammation and prevent the accumulation of disability. To test the potential neuroprotective properties of the drug, we used advanced MRI to monitor changes in myelin water fraction, T2 and T1 within lesions and normal-appearing white matter over 2 years in MS patients treated with alemtuzumab. Data suggests that, while on treatment, remyelination appears more robust possibly due to an improved immunologic milieu 6 months post-alemtuzumab. Supporting this is a smaller T1 increase at new lesion appearance indicating less edema and inflammation for lesions formed while under the effects of alemtuzumab.

Vanessa Wiggermann^1,2, Inga Ibs^2,3, Stephanie M. Schoerner^2,4, Enedino Hernández Torres^2,5, Luanne Metz⁶, David K.B. Li^2,7, Anthony Traboulsee^5,7, and Alexander Rauscher^2,5
1Physics and Astronomy, Univerisity of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³University of Osnabrueck, Germany, ⁴Technical University of Dortmund, Germany, ⁵UBC MRI Research Centre, Vancouver, BC, Canada, ⁶Clinical Neurosciences, University of Calgary, Calgary, AB, Canada, ⁷Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada

Clinically isolated syndrome (CIS) patients experience demyelinating events, without fulfilling the criteria for clinically definite multiple sclerosis (MS). Here, we investigated changes in lesions, normal appearing and diffusely abnormal white matter in a CIS cohort using MR frequency shift imaging. Over 2 years no changes were observed in normal appearing and diffusely abnormal white matter, while new MS lesions showed changes in the MR frequency signal before enhancement, a steep increase during their formation and elevated frequency for 12 months after lesion formation.

Thomas W. Johnson^1,2, Linhui Yu³, Kartikeya Murari³, and Jeff F. Dunn^1,2
1Radiology, University of Calgary, Calgary, Alberta, Canada, ²Hotchkiss Brain Institute, Calgary, Alberta, Canada, ³Electrical Engineering, University of Calgary, Calgary, Alberta, Canada

Cerebral metabolic rate of oxygen consumption was measured in the cortex of mice with long term (day 36 post induction) experimental autoimmune encephalomyelitis, a model of multiple sclerosis. A multimodal MRI / near-infrared spectroscopy system was used to measure cerebral blood flow and capillary hemoglobin saturation respectively. Arterial saturation was monitored using a pulse oximeter. The control mice (n=8) were found to have a CMRO2 of 2.69 ± 0.84 mL µmol O2/g/min, and the experimental mice (n=3) be 6.09 ± 1.14 µmol O2/g/min, with p < 0.001. This abnormal metabolism could be due to uncoupled mitochondria, and may point to neurodegeneration.

Blessy Mathew¹, Mark J. Lowe¹, Pallab Bhattacharyya¹, and Rob Bermel^1
1Cleveland Clinic, Cleveland, OH, United States

Our focus was to investigate use of fMRI in the recovery process in multiple sclerosis patients with optic neuritis (ON). Recovery from ON is variable with most patients making good recovery but some noticing residual deficits. We stimulated each eye with varying contrast visual and a flashing quadrant paradigms. We observed significant correlations in the affected eye between macular volume and low contrast stimuli (2.5%: p<0.049, 1.25%:p<0.003), and average quadrant (p<0.020) volumes, and between retinal nerve fiber layer thickness and lowest contrast stimuli (1.25%:p<0.024), and average quadrant volume (p<0.003). No correlations were observed in the unaffected eye.

Courtney A Bishop^1,2, Jean SZ Lee³, Charlotte L Thomas⁴, Rebecca Quest⁵, Lesley Honeyfield⁵, Paolo A Muraro^2,6, Adam D Waldman^2,5, and Rexford D Newbould^1,7
1Image Analysis Department, Imanova Centre for Imaging Sciences, London, United Kingdom, ²Division of Brain Sciences, Imperial College London, London, United Kingdom, ³Radiology Department, Oxford University Hospitals NHS Trust, Oxford, United Kingdom, ⁴Department of Medicine, St George's Hospital, London, United Kingdom, ⁵Department of Imaging, Imperial College Healthcare NHS Trust, London, United Kingdom, ⁶Department of Clinical Neurosciences, Imperial College Healthcare NHS Trust, London, United Kingdom, ⁷Division of Experimental Medicine, Imperial College London, London, United Kingdom

Volumetric T1 and T2-weighted volumes were acquired on 38 MS patients with average disease duration of 2 years, but grouped into two age brackets, and 52 age-group matched controls. Manually delineated white matter (WM) and grey matter (GM) lesions were lesion-filled in the automated segmentation of GM and WM with Sienax and FIRST. WM volumes were not significantly different between early MS subjects and controls, however, GM and especially non-peripheral GM volumes were, such as in the thalamus and putamen (P<0.001 in each). The younger MS group had significantly reduced volume in the caudate and the hippocampus (P<0.001 for both), which was not reflected in the older group.

Tim Sinnecker¹, Sophie Hahndorf¹, Katharina Mueller¹, Petr Dusek^2,3, Lutz Harms^4,5, Sanjeev Chawla⁶, Thoralf Niendorf^7,8, Ilya Kister⁹, Friedemann Paul^1,4, Yulin Ge⁶, and Jens Wuerfel^1,2
1NeuroCure Clinical Research Center, Charité- Universitaetsmedizin, Berlin, Berlin, Germany, ²Institute of Neuroradiology, Universitaetsmedizin Goettingen, Niedersachsen, Germany, ³1st Faculty of Medicine and General University Hospital in Prague, Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, Praha, Czech Republic, ⁴Experimental and Clinical Multiple Sclerosis Research Center, Charité Universitaetsmedizin Berlin, Berlin, Germany, ⁵Department of Neurology, Charité - Universitaetsmedizin Berlin, Berlin, Germany, ⁶Department of Radiology, NYU School of Medicine, New York, NY, United States, ⁷Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Germany, ⁸Max Delbrueck Center for Molecular Medicine, Experimental and Clinical Research Center, Charité - Universitaetsmedizin Berlin, Berlin, Germany, ⁹Multiple Sclerosis Care Center, Department of Neurology, NYU School of Medicine, New York, NY, United States

Differentiating between seronegative Neuromyelitis optica (NMO) and multiple sclerosis (MS) with e.g. spinal predominance has remained challenging in clinical routine. Small supratentorial white matter lesions suggestive for MS may also be observed on conventional MRI in NMO. Here we studied the potential of highly resolving phase contrast MRI at 7 Tesla (T) that provides additional information on the tissue microstructure in differentiating NMO lesions from MS plaques. We observed unique morphological features of NMO and MS plaques. Hence, phase contrast MRI can be used to improve the distinction between NMO and MS brain lesions.

Jacob Alois Matusinec¹, Zahra Hosseini², Junmin Liu³, David A Rudko⁴, Matthew P Quinn³, Marcelo kremenchutzky⁵, Ravi Menon^3,6, and Maria Drangova^3,7
1Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, ²Biomedical Engineering Graduate Program, Western University, Ontario, Canada, ³Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, Canada, ⁴Brain Imaging Centre Montreal Neurological Hospital and Institute, McGill University, Quebec, Canada, ⁵Department of Clinical Neurological Sciences, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, ⁶Centre for Functional and Metabolic Mapping, Robarts Research Institute, Western University, London, Ontario, Canada, ⁷Department of Medical Biophysics Schulich School of Medicine & Dentistry, Western University, Ontario, Canada

MS lesions tend to be associated with a central vein. Recent advances in MRI technology may allow researchers and clinicians to view these venocentric lesions to accurately diagnose MS. In this study we localized lesions using FLAIR images, then used a novel 7T SWI technique (IEV-SWI) to obtain high-quality venograms and calculate the percent of lesions with a central vein (%LCV). We found a very high average %LCV from three observers (94.6 ± 5.1%, 97.4 ± 4.0%, and 86.4 ± 3.8%) in five MS patients suggesting IEV-SWI may be a useful method for detecting small veins in MS lesions.

Lijie Tu^1,2, Yan Zhang^1,3, Ajay Gupta¹, Joseph Comunale¹, Thanh Nguyen¹, Susan Gauthier⁴, and Yi Wang^1,5
1Radiology, Weill Cornell Medical College, New York, NY, United States, ²Applied & Engineering Physics, Cornell University, Ithaca, NY, United States, ³Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technoology, Wuhan, Hubei, China, ⁴Neurology, Weill Cornell Medical College, New York, NY, United States, ⁵Biomedical Engineering, Cornell University, Ithaca, NY, United States

During an multiple sclerosis (MS) lesion formation, first there is acute blood-brain-barrier breakdown (gadolilnium (Gd) enhancing) and demyelination, reducing subvoxel structure heterogeneity or R2*. Then there is subacute clearance of myelin debris by microglia/macrophages (m/M) and further inflammation by m/M laden with iron, increasing susceptibility as measured on QSM. We found most Gd-enhancing lesions are R2* hypointense and QSM isointense. Without using Gd injection, the sensitivity to identify Gd-enhancing lesions as isointense on QSM, is 89%, and the specificity is 97%.

Gabriel KOCEVAR¹, Claudio STAMILE¹, Salem HANNOUN¹, Francois COTTON^1,2, Françoise DURAND-DUBIEF^1,3, and Dominique SAPPEY-MARINIER^1,4
1CREATIS (CNRS UMR5220 & INSERM U1044), Université Lyon 1, INSA-Lyon, Villeurbanne, France, ²Service de Radiologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Benite, France, ³Service de Neurologie A, Hôpital Neurologique, Hospices Civils de Lyon, Bron, France, ⁴CERMEP - Imagerie du Vivant, Université de Lyon, Bron, France

We introduce a new graph theory based method to characterize brain connectivity alterations occurring in Multiple Sclerosis (MS) patients brain networks. Adjacency matrices were computed from the diffusion and anatomical MRI. Global metrics were then estimated. A global alteration of brain network was shown in the three patients forms, hence demonstrating the ability and the sensitivity of this technique to characterize alterations and plasticity of brain connectivity. Thereby offering the potential to better characterize MS patients’ clinical status and better predict disease evolution.

Petra Schmalbrock¹, Mary Russell¹, Grant K Yang¹, Jacqueline A Nicholas², Michael V Knopp¹, and David Pitt^3
1Radiology, The Ohio State University, Columbus, Ohio, United States, ²Neurology, The Ohio State University, Columbus, Ohio, United States, ³Neurology, Yale School of Medicine, New Haven, CT, United States

Basal ganglia iron was assessed in 29 MS patients using CSF-normalized T2-weighting, T2 relaxometry and QSM at 7T. All three methods produced similar results, most notably regional variability within the three analyzed structures (globus pallidus, putamen and caudate) was consistently seen with all methods. This variability has to be taken into account in future analysis and may relate to the functional anatomy of the basal ganglia.

Guillaume Duhamel¹, Arnaud le Troter¹, Valentin Prevost¹, Gopal Varma², Maxime Guye¹, Jean-Philippe Ranjeva¹, Jean Pelletier³, David C. Alsop², and Olivier M. Girard^1
1Aix Marseille University, CRMBM / CNRS UMR 7339, Marseille, France, ²Department of Radiology, BIDMC, Harvard Medical School, Boston, MA, United States, ³Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital La Timone, Marseille, France

Inhomogeneous Magnetization Transfer (ihMT) has recently been proposed for specific myelin imaging. In this study we evaluated the sensitivity of ihMT for MS pathology and compared it to classical MT.

Matthew P Quinn^1,2, Joseph S Gati¹, L Martyn Klassen¹, Marcelo Kremenchutzky³, and Ravi S Menon^1,2
1Centre for Functional and Metabolic Mapping, Robarts Research Institute, Western University, London, Ontario, Canada, ²Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, ³Department of Clinical Neurological Sciences, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada

A cohort of patients with clinically isolated syndromes suggestive of early MS and a cohort of age- and sex-matched healthy controls were followed for 12 to 20 months with imaging every 4 months. Rates of iron accumulation (R2*) in grey matter nuclei as well as rates of brain volume loss were compared between groups. Patients had increased iron accumulation in putamen and thalamus, as well as significantly increased brain volume loss. Thalamic iron measurements were significantly associated with brain volume percentage change after correction for age and time on-study. These results suggest iron deposition and atrophy occur in early MS.

Christopher Nishioka¹, Jennifer Mei², Hsiao-Fang Liang³, Wei-Xing Shi⁴, and Shu-Wei Sun^5,6
1Neuroscience, UC Riverside, Riverside, California, United States, ²Basic Science, Loma Linda University, Loma Linda, United States, ³Basic Science, Loma Linda University, Loma Linda, CALIFORNIA, United States, ⁴Pharmaceutical Science, Loma Linda University, California, United States, ⁵Basic Science and Radiation Medicine, Loma Linda University, California, United States, ⁶Neuroscience and Bioengineering, UC Riverside, California, United States

Optic neuritis is usually the first symptom of multiple sclerosis (MS). This condition and its underlying pathology can be detected in vivo using diffusion tensor imaging (DTI) or visually evoked potentials (VEPs). While these two techniques are both sensitive, they measure very different phenomena. DTI measures structural disruption of axons and myelin, while VEPs measure neural conductivity. The sensitivity of both techniques to early MS pathology and their relationship to each other remains unclear. This study addresses these questions and examines DTI and VEP changes in a model of optic neuritis across a time-course.

Mário João Fartaria de Oliveira^1,2, Guillaume Bonnier^1,3, Alexis Roche^1,3, Tobias Kober^1,3, Reto Meuli⁴, David Rotzinger⁴, Myriam Schluep², Renaud Du Pasquier², Jean-Philippe Thiran^3,4, Gunnar Krueger^1,3, Cristina Granziera^1,2, and Meritxell Bach Cuadra^4,5
1Advanced Clinical Imaging Technology, Siemens Healtcare IM BM PI & Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne (CHUV), Lausanne, Switzerland, ²Neuro-immunology Unit and Laboratoire de Recherché en Neuroimagérie (LREN), Neurology Division, Centre Hospitalier Universitaire Vaudois and University of Lausanne (CHUV), Lausanne, Switzerland, ³Signal Processing Laboratory, LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁴Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne (CHUV), Lausanne, Switzerland,⁵Signal Processing Core, Centre d'Imagerie BioMédicale (CIBM), Lausanne, Switzerland

Advanced Magnetic Resonance Imaging (MRI) plays an important role for lesion visualization in Multiple Sclerosis (MS). This work aims to study the contribution of advanced MRI on the performance of an automated tool for lesion detection. The method is based on a supervised approach and the impact on detection performance of different advanced MRI sequences was evaluated through different combinations of features in the classification process. The validation was done in a cohort of thirty-nine early MS patients through a ground truth obtained from manual segmentations by a neurologist and a radiologist.

Maxime Donadieu^1,2, Yann Le Fur^1,2, Andrew A Maudsley³, Angèle Lecocq^1,2, Wafaa Zaaraoui^1,2, Elisabeth Soulier^1,2, Marie-Liesse Lesage^1,2, Sulaiman Sheriff³, Mohammad Sabati³, Sylviane Confort-Gouny^1,2, Maxime Guye^1,2, Jean Pelletier^1,4, Bertrand Audoin^1,4, and Jean-Philippe Ranjeva^1,2
1CRMBM UMR CNRS 7339, Aix Marseille Université, Marseille, France, Metropolitan, ²CEMEREM, Pole d'imagerie médicale, Hopital la Timone, AP-HM, Marseille, France, Metropolitan, ³Department of Radiology, Miller School of Medicine University of Miami, Miami, Florida, United States, ⁴Department of Neurology, Timone University Hospital, Marseille, France, Metropolitan

Using weighted mean of two tilted whole brain 3D-1H EPSI acquisitions acquired in 15 healthy controls, we built metabolic templates of NAA, Glux, tCr, Cho and m-Ins spatially normalized in the MNI atlas. Similar data obtained in 8 RRMS patients allowed to conducting multi-metabolite statistical mapping analyses to evidence patterns of metabolic abnormalities involving decreases in NAA, Glux and Cho, as well as increases in tCr and m-Ins in line with neuronal dysfunction, activated microglia and cellular loss. These data support the promising contribution of statistical mapping analyses applied to whole brain 3D-MRSI to study pathophysiological processes associated to MS.

MS 2

Wednesday 3 June 2015

Antje Arnold^1,2, Jiangyang Zhang^1,2, Guanshu Liu^1,3, Agatha Lyczek^1,2, Miroslaw Janowski^1,4, Jeff W.M. Bulte^1,2, and Piotr Walczak^1,2
1Dept. of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²Cellular Imaging Section, Institute for Cell Engineering, Baltimore, Maryland, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ⁴NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

Recent advances in regenerative medicine raise hope that the transplantation of human GRPs may be an effective approach to restore brain function in patients who suffer from myelin disorders. The detection of remyelination is still quite challenging with non-invasive MR imaging methods. The goal of our study was to improve the utility of non-invasive MR imaging for evaluation of myelination by human GRPs. Here we show that T2-w and quantitative magnetization transfer imaging revealed myelination after transplantation of hGRPs in a dysmyelinated mouse model. However, diffusion tensor imaging data did not show significant improvement compared to non-transplant controls.

Eric Mathew Schrauben¹, Kevin M Johnson¹, Oliver Wieben^1,2, and Aaron Field^3
1Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, United States, ²Radiology, University of Wisconsin - Madison, Wisconsin, United States,³Radiology, University of Wisconsin - Madison, Madison, Wisconsin, United States

In patients with MS and age/sex-matched healthy controls, metrics of diffusion, magnetization transfer, and perfusion in normal-appearing white matter and flow parameters using 4D flow MRI are compared.

Pedro A. Gómez^1,2, Tim Sprenger^1,2, Ana A. López¹, Jonathan I. Sperl², Brice Fernandez³, Miguel Molina-Romero^1,2, Xin Liu^1,2, Vladimir Golkov^1,2, Michael Czisch⁴, Philipp Saemann⁴, Marion I. Menzel², and Bjoern H. Menze^1
1Technical University Munich, Munich, Germany, ²GE Global Research, Munich, Germany, ³GE Healthcare, Munich, Germany, ⁴Max Plank Institute of Psychiatry, Munich, Germany

This work proposes to use scalar features calculated from diffusion MR data alongside structural MR intensities in the automated segmentation of Multiple Sclerosis (MS) lesions. We acquired and processed multi-contrast MR data from 7 MS patients, used random forests to segment lesions, and evaluated our method via DICE scores, achieving scores over 0.65. Finally, we made use of the random forest framework to assess the discriminative power of the estimated features. We show that diffusion features estimated from the diffusion tensor are as discriminative as T1 and T2 intensities for the classification task.

Marios C. Yiannakas¹, Ahmed Mustafa¹, Benjamin De Leener², Hugh Kearney¹, David H. Miller¹, Julien Cohen-Adad², and Claudia A. M. Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, WC1N3BG, United Kingdom, ²Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada

In this work a fully automated spinal cord segmentation method (PropSeg) is evaluated in a large cohort of people with multiple sclerosis (MS). Measurements of cervical cord cross-sectional area (CSA) were obtained and compared with those obtained through an established semi-automated method which is based on an active surface model. The results from this study suggest that PropSeg is a user-friendly, reliable and time-efficient way of obtaining CSA measurements and if validated in future studies it may prove a promising approach for analysis of large datasets in therapeutic trials in MS.

Afaf S Elsarraj¹, Paul S Morgan², Cris S Constantinescu³, Dorothee P Auer¹, and Robert A Dineen^1
1Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ²Medical Physics, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, ³Clinical Neurology Group, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom

Haemodynamic changes have been reported in multiple sclerosis (MS), using MRI techniques. However, the extent to which the perfusion alterations detected are comparable between these techniques is not well understood. In this study we used arterial spin labelling (ASL) and dynamic contrast enhance-MRI (DCE-MRI) to test whether these two techniques are comparable, by comparing cerebral blood flow (CBF) values from basal ganglia in a cohort of MS patients and matched healthy controls. Our findings suggest that DCE-MRI is more sensitive than ASL in measuring perfusion in multiple sclerosis.

Md Nasir Uddin¹, R Marc Lebel¹, Peter Seres¹, Gregg Blevins², and Alan H Wilman^1
1Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada, ²Division of Neurology, University of Alberta, Edmonton, Alberta, Canada

Abnormal iron accumulation in subcortical grey matter is a consistent finding in patients with multiple sclerosis. We demonstrate the time course of spin echo transverse relaxation rate R₂ and brain atrophy in subcortical grey matter and their relationship with multiple sclerosis disease severity using 4.7 T over two years.

Katherine A Koenig¹, Mark J Lowe¹, Darlene K Stough², Lisa Gallagher², Dwyer Conklyn³, and Francois Bethoux^2
1The Cleveland Clinic, Cleveland, Ohio, United States, ²Neurological Institute, The Cleveland Clinic, Cleveland, Ohio, United States, ³DBC3 Music Therapy, Independence, Ohio, United States

This work assesses the impact of rhythmic auditory stimulation on functional activation during mental imagery of walking in patients with multiple sclerosis.

Robert L Harrigan¹, Katrina M Nelson¹, Lindsey M Dethrage², Robert L Galloway³, Bennett A Landman^1,2, Louise A Mawn⁴, and Seth A Smith^2,5
1Electrical Engineering, Vanderbilt University, Nashville, TN, United States, ²Institute for Imaging Science, Vanderbilt University, Nashville, TN, United States,³Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ⁴Ophthalmology and Neurological Surgery, Vanderbilt University, Nashville, TN, United States, ⁵Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States

Patients presenting with optic neuritis (ON), a sudden inflammation of the optic nerve which impairs vision, have an increased likelihood of developing MS. We investigate a recently developed fully-automatic method for delineation of the optic nerve and surrounding CSF. Scans were acquired for a population of 26 relapsing-remitting MS patients and 32 healthy controls with a high contrast T2-weighted VISTA on a 3T Philips Achieva. Results show significantly decreased optic nerve radii posterior to the globe in MS patients with ON (14 of 26). MS patients (12 of 26) without ON show no significant deviation compared to the control population.

Yulin Ge¹, Ilya Kister², Sanjeev Chawla¹, Tim Sinnecker³, Jean-Christophe Brisset¹, Joseph Herbert², Friedemann Paul³, and Jens Wuerfel^3
1Radiology, NYU Langone Medical Center, New York City, NY, United States, ²Neurology, NYU Langone Medical Center, New York, United States,³Universitätsmedizin Göttingen, Berlin, Germany

In vivo evaluation of cortical pathology is still currently challenging. Using ultra-high field 7T MRI, this study showed different types of cortical lesions that are not visible on conventional field-strength MRI, and updated lesion signal, morphology, and the extent of cortical involvement. In particular, higher prevalence of hypointense cortical lesions found in this study may have critical clinical value regarding hemorrhagic susceptibility or unfavorable drug effects in MS patients.

Jamie Campbell¹, Dawn Langdon², Waqar Rashid³, and Mara Cercignani^1
1Clinical Imaging Sciences Centre, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom, ²Neuropsychology, University of London, London, United Kingdom, ³Neurology, Brighton & Sussex University Hospitals NHS Trust, Brighton, East Sussex, United Kingdom

Multiple sclerosis (MS) is a common inflammatory condition affecting the CNS. Between 40-60% of individuals with MS have evidence of cognitive dysfunction. We investigate if a period of computerised, home-based cognitive rehabilitation is effective in improving cognitive performance. Patients with MS and evidence of cognitive impairment were randomly assigned to receive 45-minute, thrice weekly sessions of home-based computerised cognitive training for six weeks or a placebo condition. We present data on the first 17 patients recruited. fMRI was performed during a N-back test. Improvements in n-back performance were observed following training with decreased frontal lobe activations in the treatment group.

Amal Samaraweera¹, Margareta Clarke², Olivier Mougin³, Rob Dineen⁴, Ian Driver³, Paul S Morgan⁵, and Nikos Evangelou^1
1Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom, ²Clinical Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, ³Sir Peter Mansfield MR Centre, University of Nottingham, Nottingham, United Kingdom, ⁴Department of Neuroradiology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, ⁵Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

BACKGROUND: There are many MRI mimics of MS which can cause diagnostic uncertainty. FLAIR* allows better visualisation of white matter lesions and central veins which are common in MS. We produced a FLAIR* image at 3T without contrast agent to analyse MS and ischaemic lesions. METHODS: Two observers compared the ability of FLAIR* to standard T2*-weighted imaging in detecting lesions and central veins. RESULTS: FLAIR* could detect as many lesions and central veins as T2* CONCLUSIONS: FLAIR* can differentiate MS from ischaemic lesions at 3T without contrast agent. Prospective studies will determine if this can be used as an imaging biomarker.

Juergen Baudewig¹, Giulia Poggi², Hannelore Ehrenreich², and Susann Boretius^1
1Section Biomedical Imaging, Dept. of Radiology and Neuroradiology, Christian-Albrechts-University Kiel, Kiel, Germany, ²Max Planck Institute of Experimental Medicine, Goettingen, Germany

Heterozygous Shiverer mice with mild myelin alteration reductions serve as a model for age-related mental disorders. In this study we demonstrate that these mild changes (1) can be detected by magnetization transfer techniques, (2) have metabolic consequences and (3) changes progress with age. The subtle myelin alterations were best detectable by MT saturation. DTI failed to differentiate affected mice probably due to the nature of myelin alterations. MRS revealed changes in total creatine and taurine and may indicate altered energy metabolism. These findings probably contribute to an better understanding of the role of myelin proteins in development of mental disease.

Bailey Lyttle¹, Adrienne Dula^2,3, Benjamin Conrad², Richard Dortch^2,3, Megan Barry⁴, Subramaniam Sriram⁴, Shilpa Reddy⁴, Seth Smith^2,3, and Siddharama Pawate^4
1Neuroscience, Vanderbilt University, Nashville, Tennessee, United States, ²Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ³Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Neurology, Vanderbilt University, Nashville, TN, United States

Nearly all patients of multiple sclerosis experience deficits in movement initiation and somatosensory stimulation, indicating the progression of lesions and atrophy within the spinal cord. However, clinical (1.5T) and low-field (3T) MRI fail to reflect the level of spinal cord damage necessary to produce such extensive physical impairment, creating a clinical-radiological paradox. The application of high-field (7T) MRI and semi-automatic segmentation correlates clinical performance not only with spinal cord atrophy but also with lesion load, suggesting that the clinical-radiological paradox can be resolved by increasing the field strength at which peripheral effects of multiple sclerosis are identified.

Noam Ben-Eliezer^1,2, Veronica Cosi¹, Akio Yoshimoto¹, Daniel K Sodickson^1,2, Mary Bruno¹, Kai Tobias Block^1,2, and Timothy M Shepherd^1,2
1Center for Biomedical Imaging, Department of Radiology, New York University Medical Center, New York, NY, United States, ²Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University School of Medicine, New York, NY, United States

Accurate quantification of T₂ values in vivo is a long-standing challenge hampered by the inherent inaccuracy of rapid multi-SE sequences. This bias is, moreover, inconsistent and dependent on the pulse sequence scheme and parameter-set employed, and hence changes between scanners or vendors. We employ a recently-developed T₂ mapping technique – the echo-modulation curve (EMC) algorithm – to quantitatively classify brain tissues in MS patients. Preliminary results suggest that the high accuracy and stability afforded by the EMC approach allows to uncover statistically significant differences which would otherwise be buried beneath the inherent scanner- or protocol-dependent variability of traditional T₂ mapping approaches.

Valentin H. Prevost¹, Angele Viola¹, Olivier M. Girard¹, Adriana T. Perles-Barbacaru¹, Jennifer Tracz¹, Gopal Varma², David C. Alsop², and Guillaume Duhamel^1
1CRMBM CNRS UMR 7339, Aix-Marseille University, Marseille, France, ²Departement of radiology, BIDMC, Harvard Medical School, Boston, MA, United States

Inhomogeneous magnetization transfer (ihMT) imaging has been recently proposed as new technique for myelin imaging. Whereas it preclinical feasibility has been demonstrated, it sensitivity for myelin disorders pathology (e.g. multiple sclerosis (MS)) remains to be assessed. The purpose of this study was to investigate the sensitivity of ihMT for a murine model of experimental autoimmune encephalomyelitis (EAE) induced with the MOG peptide.

Yong Wang^1,2, Peng Sun¹, Qing Wang¹, Kathryn Trinkaus³, Robert T. Naismith⁴, Robert E. Schmidt⁴, Anne H. Cross^2,4, and Sheng-Kwei Song^1,2
1Radiology, Washington University in St. Louis, Saint Louis, MO, United States, ²Hope Center for neurological Disorders, Washington University in St. Louis, Saint Louis, MO, United States, ³Biostatistics, Washington University in St. Louis, Saint Louis, MO, United States, ⁴Neurology, Washington University in St. Louis, Saint Louis, MO, United States

The accuracy of diffusion MRI as biomarkers of white matter (WM) damage has been significantly compromised by the presence of fiber crossing and CSF contamination. Accurate diffusion MRI biomarkers of WM damage requires to correctly model the effect of crossing fibers and CSF contamination. Against this background, we demonstrate the capability of recently developed diffusion basis spectrum imaging (DBSI) to reliably quantify the diffusion properties of normal and injured WM tracts with confounding fiber crossing and CSF contamination.

Emma Biondetti¹, Jonathan D. Clayden², Matteo Pardini^3,4, Alessandra Bertoldo⁵, Declan T. Chard⁴, and Claudia A. M. Wheeler-Kingshott^4
1UCL Department of Medical Physics and Biomedical Engineering, University College London, London, England, United Kingdom, ²Developmental Imaging and Biophysics Section, UCL Institute of Child Health, University College London, London, England, United Kingdom, ³Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy, ⁴NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ⁵University of Padova, Padova, Italy

In this work we identify a relevant pattern of connectivity between distinct areas of the brain cortex, based on data of healthy subjects. We weight the links between regions using either grey matter-derived or white matter-derived anatomical measures, forming two connectivity networks. We show that these networks detect the connectivity impairment that occurs in multiple sclerosis patients, therefore we suggest them as a tool for monitoring disease-related connectivity changes. We also show that these two networks reveal information about complementary systems, enabling the evaluation of connectivity damage due to modifications of different structures in the brain.

Weiwei Chen¹, Yan Zhang¹, Wenzhen Zhu¹, Ketao Mu¹, Chu Pan¹, Susan A. Gauthier², and Yi Wang^3
1Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science& Technology, Wuhan, Hubei, China, ²Neurology, Weill Cornell Medical College, New York, United States, ³Radiology, Weill Cornell Medical College, New York, United States

A total of 70 consecutive clinical confirmed MS patients and 26 age and gender matched healthy controls (HCs) who underwent quantitative susceptibility mapping (QSM) were retrospectively selected in this study to assess the susceptibility of NAWM and its correlation with MS lesions’ susceptibility variation and clinical features in MS patients. This study suggests the following findings. 1) The NAWM of MS patients showed significantly higher susceptibility than NWM of HCs. 2) The NAWM of patients with Gd-enhanced lesions showed a similar susceptibility to HCs NWM, while the NAWM of MS patients without Gd-enhanced lesions showed significantly higher susceptibility than both healthy controls NWM and the NAWM of patients with Gd-enhanced lesions. 3) The susceptibility of NAWM was positively correlated with the increase of MS lesions’ susceptibilities.

Yelong Shen¹, Tianyi Qian², Yanbing Wang³, Guangbin Wang¹, and Bin Zhao^1
1Shandong Medical Imaging Research Institute, School of Medicine, Shandong University, Jinan, Shandong, China, ²MR Collaborations NE Asia, Siemens Healthcare, Beijing, China, ³Rizhao People's Hospital of Shandong, Shandong, China

Due to the effect of the cerebrospinal fluid, the surrounding fat and the thin structure of the spinal cord, routine T2w-TSE imaging of the spinal cord is limited, with a high chance of missed diagnosis or misdiagnosis. This study compared the imaging of DIR and T2w in demyelinating disease to find out which one has a higher diagnostic value. The results demonstrates that SPACE-DIR has significantly higher CNR and found more lesion than T2-TSE in detecting lesion in cervical and thoracic cord for demyelinating disease diagnosis.

Patricia Alves Da Mota¹, Marios C Yiannakas¹, Ferran Prados^1,2, Manuel Jorge Cardoso¹, David Paling³, Frank Riemer¹, Daniel Tozer⁴, Sébastien Ourselin¹, David H Miller¹, Xavier Golay⁵, Claudia AM Wheeler-Kingshott¹, and Bhavana S Solanky^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Department of Medical Physics and Bioengineering Wolfson House, Translational Imaging Group CMIC, London, England, United Kingdom, ³Department of Clinical Neurosciences, University of Sheffield, Sheffield, England, United Kingdom, ⁴Department of Clinical Neurosciences, University of Cambridge, Cambridge, England, United Kingdom,⁵NMR Research Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, England, United Kingdom

In this study we look at the relationship between total sodium concentration (TSC) and T2 in multiple sclerosis, both of which are sensitive to demyelination. ¹H T2 increases are seen as the myelin water fraction reduces due to demyelination. A TSC increase is also expected as a result of demyelination, which causes an over-expression of sodium channels along the axon. However, increased TSC also occurs if extracellular space increases due to cell swelling or degradation. Here we look at the interaction between TSC and T2 in NAWM, NAGM, CSF, T1 and T2 lesions, in relapsing remitting and secondary progressive MS.

Yong Wang^1,2, Peng Sun¹, Qing Wang¹, Kathryn Trinkaus³, Robert T. Naismith⁴, Robert E. Schmidt⁴, Anne H. Cross^2,4, and Sheng-Kwei Song^1,5
1Radiology, Washington University in St. Louis, Saint Louis, MO, United States, ²Hope Center for neurological Disorders, Washington University in St. Louis, Saint Louis, MO, United States, ³Biostatistics, Washington University in St. Louis, Saint Louis, MO, United States, ⁴Neurology, Washington University in St. Louis, Saint Louis, MO, United States, ⁵Hope Center for neurological Disorders, Washington University in St. Louis, Saint Louis, m, United States

Diffusion tenor imaging (DTI) radial diffusivity (RD) and magnetization transfer ratio (MTR) are known sensitive to myelin integrity. However, the specificity of DTI and MTR are suboptimal. In this study, both histological myelin quantification and diffusion MRI were conducted on MS spinal cord specimens to assess the effect of extra-cellular tissue water on the specificity of DTI RD. Preliminary findings suggested that extra-cellular tissue water confounded myelin imaging specificity of DTI RD. Findings were also extended to diffusion MRI and MTR of living patients. By differentiating extra-cellular tissue water, myelin imaging specificity can be significantly improved by diffusion basis spectrum imaging (DBSI).

Hagen H Kitzler¹, Caroline Koehler¹, Hannes Wahl¹, Tjalf Ziemssen², and Sean C Deoni^3
1Neuroradiology, Technische Universitaet Dresden, Dresden, SN, Germany, ²Neurology, Technische Universitaet Dresden, Dresden, SN, Germany, ³Engineering, Brown University, Providence, RI, United States

In Multiple Sclerosis, an ongoing debate exists on whether the disease is associated with remarkable differences of underlying pathology and variable subsequent degree of myelin loss within focal demyelinating white matter lesions in early disease states. A rapid, reliable whole-brain myelin imaging analysis method would allow the direct testing of this hypothesis. In fact, the in vivo observation of lesional myelination changes would provide a direct tool to detect response to new individualized therapeutic approaches enhancing the intrinsic repair termed remyelination. We present a method to retrieve the individual myelination status of demyelinating lesions and their change over time from mcDESPOT data.

Sanjeev Chawla¹, Olga Marshall¹, Jean Christophe Brisset¹, Hanzhang Lu², Ilya Kister³, and Yulin Ge^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ³Neurology, New York University Langone Medical Center, New York, NY, United States

To evaluate longitudinal changes in venous oxygenation (Yv) from superior sagittal sinus in multiple sclerosis (MS), 17 patients underwent T2-relaxation-under-spin-tagging imaging at an interval of 2 years. Twenty-one controls were also included. Significantly elevations in CPMG-T2 (68.24±10.64ms vs 59.65±7.13ms, p=0.01) and Yv (62.1±6.25% vs 58.2±4.08%, p=0.03) were observed from MS patients compared to healthy controls. Compared to baseline, a significant increase in CPMG- T2 was observed at follow-up time point (68.24±10.64ms vs. 95.46±18.46ms). Similarly, a significant increase in Yv was observed at follow-up (62.1±6.25% vs. 74.82±6.51%). TRUST may be a useful technique for assessing longitudinal variations in Yv in MS.

Tom Dresselaers¹, Kristof Govaerts¹, James Dooley^2,3, Uwe Himmelreich¹, Adrian Liston^2,3, and Kim A. Staats^2,3
1Dept of Imaging and Pathology, KU Leuven, Leuven, Leuven, Belgium, ²Autoimmune Genetics Laboratory, VIB, Leuven, Belgium, ³Dept. of Microbiology and Immunology, KU Leuven, Leuven, Belgium

In this study anatomical imaging and DTI is used to confirm in vivo the expected demyelination in a novel myelin basic protein mutant that spontaneously developed in our colony. Anatomical imaging and T2 relaxometry and DTI readouts reflect typical changes as also seen in other demyelination models such as the Shiverer mice.

Brain Tumour Advanced Methods

Wednesday 3 June 2015

Ajay Nemani¹, Mirko Vukelich¹, Kristina Wakeman², Tibor Valyi-Nagy², and Keith Thulborn^1
1Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States, ²Pathology, University of Illinois at Chicago, Chicago, IL, United States

The spatial distribution of permeability (Ktrans) and blood volume (Vb) as derived from dynamic contrast enhanced (DCE) MRI and the extended Tofts model has been investigated in human brain tumors to establish which parameter is the earlier marker of tumor progression in grade and for defining actively growing tumor margins. Tumors were sampled with profiles extending across the center and margins of the tumors. A histological study of a resected tumor confirms growth of new vessels with normal endothelial cells with increased Vb prior to increased Ktrans.

Xiang Liu¹, Wei Tian², Rajiv Mangla², Mahlon Johnson², and Sven Ekholm^2
1Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, United States, ²University of Rochester Medical Center, NY, United States

Gliobasltoma, is the most common primary malignant and fatal brain tumor. The mTOR-EGFR pathway is important for treatment response and overall survival (OS). Our translational research found that the molecular signature of mTOR correlated with maximal rCBV ratio of peri-enhancing tumor area (rCBVperi-tumor), the patients with high rCBVperi-tumor had shorter OS, and combination of rCBVperi-tumor and mTOR could improve prediction of survival time in patients with glioblastoma.

Janine M Lupo¹, Qiuting Wen¹, Joanna J Phillips^2,3, Susan M Chang², and Sarah J Nelson^1
1Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ²Neurological Surgery, University of California, San Francisco, CA, United States, ³Pathology, University of California, San Francisco, CA, United States

In this study we propose a new method for pre-processing DSC data collected preoperatively for the analysis of image-guided tissue samples that takes a weighted average of dynamic curves based on their percentage overlap with the tissue sample mask and excludes voxels with no signal. This strategy minimized variability in parameter calculation and showed better correspondence with histopathological measures of vascular morphology than two commonly used approaches for quantification of perfusion metrics from image-guided tissue samples.

Catherine Coolens^1,2, Brandon Driscoll³, Warren Foltz⁴, and Caroline Chung^4,5
1Radiation Medicine Program, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada, ²Radiation Oncology and IBBME, University of Toronto, Toronto, Ontario, Canada, ³Radiation Medicine Program, Princess Margaret Cancer Centre, Ontario, Canada, ⁴Princess Margaret Cancer Centre, Ontario, Canada, ⁵Radiation Oncology, University of Toronto, Ontario, Canada

This study presents the evaluation of tumor perfusion and permeability of metastatic brain cancers in response to stereotactic radiation using both DCE MRI and volumetric DCE CT at similar time points throughout treatment. The aim was to evaluate the ability of DCE-MRI and DCE-CT to detect changes in tumor vascular physiology that predict for tumor response to SRS and to compare DCE-MRI analysis against DCE-CT supported by a common analysis framework to measure changes in vascular parameters in brain metastases treated with SRS.

Martin P Smith¹, Kenneth R Maravilla², Stefano Bastianello³, Eva Bueltmann⁴, Toshinori Hirai⁵, Tiziano Frattini⁶, Cesare Colosimo⁷, and Gianpaolo Pirovano^8
1Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ²University of Washington, WA, United States, ³Neuroradiology Department, University of Pavia, Pavia, Italy, ⁴Oberartzin Institut fur Diagnostiche und Interventionelle Neuroradiologie, Hannover, Germany, ⁵Kumamoto University, Kumamoto, Japan, ⁶Ospedale Valduce, Como, Italy, ⁷Policlinico “Agostino Gemelli”, Rome, Italy, ⁸Bracco Diagnostics Inc., Monroe, NJ, United States

Two-hundred-twenty nine patients with suspected brain tumors underwent two identical, randomized MRI exams at 1.5T; one enhanced with 0.1 mmol/kg gadoteridol (ProHance®) and the other with 0.1 mmol/kg gadobutrol (Gadavist®). Three blinded readers evaluated matched image sets for qualitative (lesion extent, delineation, morphology, enhancement, global preference) and quantitative (LBR, % enhancement) lesion enhancement and randomized, unmatched image sets for accuracy in lesion diagnosis vs. final clinical diagnosis. No significant differences were noted by any reader for any end-point. The results confirm that the higher concentration of the Gadavist formulation has no impact on routine morphologic imaging of brain tumors.

Dewen Yang^1
1ICON Medical Imaging, Warrington, PA, United States

Although DWI is recommended by RANO working group in the immediate postoperative MRI scan in determining whether new enhancement developing in the subsequent weeks is caused by ischemia or by tumor recurrence, DWI is not currently endorsed for differentiating treatment effect from recurrent tumor due to lack of sufficient specificity. Because changes in tumor water diffusivity can occur secondarily to changes in cell density, DWI might also be a maker for response to therapy and an early predictor of therapeutic efficacy. The roles of DWI in patients with postoperative HGG trial are reviewed along with imaging examples.

Osamu Togao¹, Akio Hiwatashi¹, Koji Yamashita¹, Kazufumi Kikuchi¹, Marc Van Cauteren², and Hiroshi Honda^1
1Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan, ²Philips Electronics Japan, Tokyo, Japan

Intravoxel incoherent motion (IVIM) has been proposed as a method to measure diffusion and perfusion using a single diffusion-weighted acquisition scheme. The both diffusion and perfusion properties are major features in determining glioma grades. In this study, we prospectively evaluated the diagnostic performance of IVIM parameters in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Both true diffusion D and perfusion fracture f were useful in the differentiation, and f showed the best diagnostic performance. IVIM imaging can be used as a noninvasive quantitative imaging method in differentiating HGG from LGG.

Rifeng Jiang¹, Wenzhen Zhu¹, Jingjing Jiang¹, Nanxi Shen¹, and Changliang Su^1
1Radiology, Tongji Hospital, Tongji Medical College, HUST, Wuhan, Hubei, China

We assessed the correlation of DKI with tumour grade and Ki-67 labelling index in glioma, and we found DKI-derived DK parameters were able to distinguish gliomas of different grades and non-invasively predict proliferative activity of glioma cells. Therefore, DKI-derived parameters(kurtosis) are more potential biomarkers.

Yi Sui^1,2, Ying Xiong^1,3, Karen Xie⁴, Frederick C. Damen¹, Xiaohong Joe Zhou^1,5, and Wenzhen Zhu^3
1Center for MR Research, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States, ²Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ³Radiology, Tongji Hospital, Wuhan, Hubei, China, ⁴Radiology, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States, ⁵Departments of Radiology, Neurosurgery and Bioengineering, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States

Fractional order calculus (FROC) diffusion model can provide additional parameters to characterizing not only the average diffusion speed, but also the complexity of tissue structures. Previous studies have shown promising results of using the FROC model to differentiate pediatric brain tumors. In this study, we have applied the FROC model to a group of adult gliomas patients and demonstrated its capability of improving the MR-based diagnostic accuracy for differentiating low-grade from high-grade gliomas.

Yan Bai¹, Carlos Torres², Zhoushe Zhao³, Dandan Zheng³, Dapeng Shi¹, Jie Tian⁴, and Meiyun Wang^1
1Henan Provincial People's Hospital, Zhengzhou, Henan, China, ²Department of Radiology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON, Canada,³GE Healthcare, Beijing, China, ⁴Institute of Automation, Chinese Academy of Sciences, Beijing, China

This study evaluated and compared the potential of diffusion-weighted imaging (DWI) using mono-exponential, bi-exponential and mono-exponential high-b values models in the grading of gliomas. The results suggested that multi-model DWI is useful in the grading of gliomas. ADChigh may become a novel parameter to reflect AQP4 expression in gliomas and guiding personalized treatment.

Peter S LaViolette¹, Elizabeth J Cochran², Nikolai Mickevicius³, Jennifer Connelly⁴, Kathleen M Schmainda^1,3, and Scott D Rand^1
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Pathology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

Infiltrative brain cancer is difficult to detect outside of contrast-enhancing regions. We introduce a new method that uses co-registered histology and brain tissue from whole brain donations to generate machine-learning based maps of cell density. We sampled regions highlighted by this new method and confirmed tumor in each location in 7 high-grade gliomas. In 5 of 7 patients, hypercellularity was found outside of contrast enhancement, and in one case outside of T2/FLAIR hyperintensity.

Chien-Yuan Eddy Lin^1,2, Bing Wu², Hung-Wen Kao^3,4, Peng Sun⁵, Yong Wang⁵, and Sheng-Kwei Song^5
1GE Healthcare, Taipei, Taiwan, ²GE Healthcare China, Beijing, China, ³Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan,⁴Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ⁵Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States

Tumor cellularity is an important indicator of aggressiveness and the efficiency of chemotherapy. Amide proton transfer (APT) imaging detects the proton exchange between bulk water and the amide protons in endogenous mobile proteins and peptides. Previous studies demonstrated that APT grading of diffuse gliomas might reflect tumor cellularity. Recently, a newly developed diffusion basis spectrum imaging (DBSI) models tissue water diffusion as a linear combination of anisotropic and isotropic diffusion tensors4, allowing the quantification of restricted and non-restricted isotropic diffusion tensor components reflecting the extent of cellularity and edema respectively. The aim of this study was to assess changes in APT and DBSI metrics in conventional MRI identified brain tumors.

Nicolas Sauwen^1,2, Diana Sima^1,2, Sofie Van Cauter³, Jelle Veraart^4,5, Alexander Leemans⁶, Frederik Maes^1,2, Uwe Himmelreich⁷, and Sabine Van Huffel^1,2
1Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium, ²iMinds Medical IT, Leuven, Belgium, ³Department of Radiology, University Hospitals of Leuven, Leuven, Belgium, ⁴iMinds Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium, ⁵Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY, United States, ⁶Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands, ⁷Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

Tissue characterization within gliomas is challenging due to the co-existence of several intra-tumoral tissue types and the high spatial heterogeneity in high-grade gliomas. An accurate and reproducible method for brain tumor characterization and the detection of relevant tumor substructures could be of great added value for tumor diagnosis, treatment planning and follow-up. In this study, a hierarchical non-negative matrix factorization (hNMF) technique is applied to multi-parametric MRI data of 24 glioma patients. hNMF can be applied on a patient-by-patient basis, it does not require large training datasets and it provides a more refined voxelwise tissue characterization compared to binary classification.

Joonsang Lee¹, Rajan Jain², Kamal Khalil³, Brent Griffith³, Ryan Bosca⁴, Ganesh Rao⁵, and Arvind Rao^1
1Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²Radiology, New York University School of Medicine, Langone Medical Center, New York, NY, United States, ³Radiology, Henry Ford Hospital, Detroit, MI, United States, ⁴Medical Physics, University of Wisconsin, Madison, WI, United States, ⁵Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

The purpose of this study was to investigate the association of the perfusion MRI textural feature ratios with overall survival rates of patients with GBM. Our study presents the results of an exploratory study demonstrating the relationship of texture feature ratios from one- and two-dimensional texture features as well as kinetic texture features with survival in patients with GBM. These findings suggest that texture feature ratios from perfusion MRI data are a promising method as a clinical prognostic tool.

Kambiz Nael¹ and Adam H Bauer^1
1Medical Imaging, University of Arizona, Tucson, AZ, United States

Solitary brain metastasis and glioblastoma multiforme (can appear similar on conventional MRI and therefore reliable imaging differentiation between MET and GBM is important for medical staging, surgical planning, and therapeutic decision making. In this study we propose and show the advantage of multiparametric MR biomarkers including fractional anisotropy and mean diffusivity derived from DTI, relative cerebral blood volume derived from DSC perfusion and microvascular permeability (Ktrans) derived from dynamic contrast enhanced perfusion towards a predictive model for differentiation of solitary metastasis from GBM.

Brent Griffith¹, Laila Poisson², Lev Bangiyev³, Jason Huse⁴, and Rajan Jain^5
1Radiology, Henry Ford Hospital, Detroit, MI, United States, ²Henry Ford Hospital, MI, United States, ³Radiology, Stony Brook University School of Medicine, NY, United States, ⁴Pathology, Memorial Sloan-Kettering Cancer Center, NY, United States, ⁵Radiology, NYU School of Medicine, New York, NY, United States

SVZ involvement in GBM patients may offer a unique location based imaging biomarker in efforts to individualize therapy and prognosis. Our work has shown that these tumors also have increased rCBV in NEL component of the tumor and worse survival as compared to cortex-originating GBMs. Poor survival and a worse vascular imaging phenotype probably reflects a more aggressive tumor, which could be attributed to the underlying differences in genomic/molecular make up and therefore, could point to a neural stem cell origin for these very heterogeneous and highly malignant tumors.

Hagen H Kitzler¹, Hannes Wahl¹, Tareq Yuratli², and Matthias Meinhardt^3
1Neuroradiology, Technische Universitaet Dresden, Dresden, SN, Germany, ²Neurosurgery, Technische Universitaet Dresden, Dresden, SN, Germany,³Neuropathology, Technische Universitaet Dresden, Dresden, SN, Germany

We used the whole-brain relaxation method Multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) to retrieve myelination information in astrocytic low-grade brain tumors and their adjacent peritumoral tissue. Little is known about the peritumoral white matter change although specific tissue changes altering the peritumoral tissue composition may precede the invasion. This feasibility study demonstrates subtle peritumoral myelin loss measurable with myelin imaging.

Jayashree Kalpathy-Cramer¹, Ville Renvall^1,2, Elizabeth Gerstner³, David Salat¹, Jean-Philippe Coutu¹, Bruce R. Rosen¹, and Jonathan R. Polimeni^1
1Radiology, MGH/Harvard Medical School, Charlestown, Massachusetts, United States, ²Brain Research Unit, O.V. Lounasmaa Laboratory, Aalto University, Espoo, Finland, ³Neuroncology, MGH/Harvard Medical School, Charlestown, Massachusetts, United States

We describe a technique to acquire high spatial and temporal resolution dynamic contrast MRI images for UFH scanners. This technique allows us to generating simultaneous quantitative T1 and T2* images. We show results from the application of this technique to a brain tumor patient and normal control

Xiaowei Zou¹, Wei Bian², Christopher P. Hess¹, Sarah J. Nelson¹, and Janine M. Lupo^1
1Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Radiology, Stanford University, Stanford, CA, United States

Manual segmentation of cerebral microbleeds is a lengthy and laborious task due to their small size, finite image resolution, large number, three-dimensional nature, various contrast, and imperfect spherical profile. In this study, we propose an automated 3-D CMB segmentation algorithm applied after automated CMB detection. Our preliminary results show that proposed method can efficiently, robustly and consistently segment CMB regions that the volume distribution of segmented CMB region on susceptibility weighted imaging at 3T and 7T are highly correlated, demonstrating it may be a reliable alternative to manual definitions.

haiyan lou¹, Rui Zhang¹, Ying Tong², Qidong Wang¹, and Shunliang Xu^1
1radiology department, No.1 Affiliated hospital, Medical School of Zhejiang University, hangzhou, zhejiang, China, ²Neurosurgery department, No.1 Affiliated hospital, Medical School of Zhejiang University, hangzhou, zhejiang, China

ESWAN showed a higher rate of angiogenesis of recurrent tumors than radiation necrosis. Observation of susceptibility signals reliably correlates with the increased tumor vascularity, particularly in recurrent tumors. In conclusion, the implemented techniques supply a qualitative method to permit prediction of tumor response. Abundant signals indicated tumor recurrence.

Daniel Coman¹, Garth Strohbehn², Liang Han³, Ragy R. T. Ragheb², Tarek M. Fahmy², Anita J. Huttner⁴, Fahmeed Hyder^1,2, Joseph M. Piepmeier³, Mark Saltzman², and Jiangbing Zhou^2,3
1Diagnostic Radiology, Yale University, New Haven, Connecticut, United States, ²Biomedical Engineering, Yale University, New Haven, Connecticut, United States, ³Neurosurgery, Yale University, New Haven, Connecticut, United States, ⁴Pathology, Yale University, New Haven, Connecticut, United States

Glioblastoma is the most common malignant tumor of the CNS. An ideal therapy for glioblastoma must be highly penetrative and must carry an effective drug payload. To address drug delivery challenges, we have developed brain-penetrating nanoparticles comprised of the FDA-approved copolymer PLGA. We demonstrated that the NPs are excellent T₂ contrast agents which allow detection at low concentration by MRI after CED to the brain and that a single administration provides controlled release of cargo agents over long time periods. Therefore, this novel drug delivery platform can have an immediate impact on monitoring of treatment in patients with glioblastoma.

Yongxian Qian¹, Charles M. Laymon², Matthew J. Oborski³, Jan Drappatz⁴, Frank S. Lieberman⁴, and James M. Mountz^2
1Qian's Lab for MRI, General Labs Cloud LLC, Pittsburgh, PA, United States, ²Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ³Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Neurology and Medicine, University of Pittsburgh, Pittsburgh, PA, United States

This work demonstrates the potential of intracellular sodium concentration as an endogenous imaging biomarker for noninvasive assessment of early response of brain tumors to therapies with radiation and chemotherapy in clinical setting. Eight patients with glioblastoma multiforme (GBM) were studied with intracellular sodium MRI on a clinical 3T scanner at three time points: baseline, 1- and 2-month follow-ups. Quantified total sodium concentration and bound (mostly intracellular) sodium concentration were used to reflect the growth or death of cancer cells in response to therapies.

Khin Khin Tha¹, Ulrich Katscher², Christian Stehning², Shigeru Yamaguchi³, Shunsuke Terasaka³, Hiroyuki Sugimori³, Toru Yamamoto⁴, Noriyuki Fujima³, Kohsuke Kudo³, Yuriko Suzuki⁵, Marc van Cauteren⁵, and Hiroki Shirato^1
1Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan, ²Philips Research Laboratories, Hamburg, Germany, ³Hokkaido University Hospital, Japan, ⁴Hokkaido University Graduate School of Health Sciences, Japan, ⁵Philips Electronics, Japan

To characterize electrical conductivity characteristics of meningiomas noninvasively, MRI including electric properties tomography (EPT) was conducted in patients with meningioma, low grade glioma, and lymphoma. The conductivity characteristics of meningiomas, conductivity variations between the tumor and adjacent gray matter, among tumor grades and subtypes, betweeen meningiomas and other tumors, were evaluated. Correlation between the conductivity and Ki67 or mean diffusivity (MD) values of meningiomas was also tested. The major histogram metrics of meningioma varied significantly from gray matter. Meningiomas had lower minimum and broader width of conductivity histograms than lymphomas. Its maximum conductivity correlated inversely with the minimum MD.

Kay Pepin¹, Arvin Arani², Nikoo Fattahi², Armando Manduca³, Richard L Ehman², John Huston III², and Kiaran McGee^2
1Graduate School, Mayo Clinic, Rochester, Minnesota, United States, ²Radiology, Mayo Clinic, Minnesota, United States, ³Physiology and Biomedical Engineering, Mayo Clinic, Minnesota, United States

Currently, no noninvasive technique exists for the accurate classification of tumor grade in glioma. Tumor mechanical properties quantified using magnetic resonance elastography may be used for the noninvasive staging of glioma. In this study, we have shown the feasibility of using MRE to quantify shear stiffness in glioma and demonstrated an inverse relationship between stiffness and tumor grade.The results of this study show the potential of using shear stiffness as a biomarker for tumor grade in glioma.

Traumatic Brain Injury

Wednesday 3 June 2015

Binjian Sun¹, Thomas G Burns¹, Tricia Z King², Laura L Hayes¹, Ana Arenivas³, Susan McManus¹, Kim E Ono¹, and Richard A Jones^1,4
1Children's Healthcare of Atlanta, Atlanta, GA, United States, ²Georgia State University, Atlanta, GA, United States, ³Kennedy Krieger Institute, Baltimore, MD, United States, ⁴Emory University, Atlanta, GA, United States

Sports Related Concussion (SRC) is a mild form of head trauma, which has been shown to primarily affect brain function rather than structure. In the current study, we used a N-Back fMRI experiment to compare the fMRI results in the acute and delayed phases of recovery from SRC with those from matched normal controls. Our results show that the acute phase of SRC reduces BOLD activation in both vigilance and working memory tasks. It also suggests that SRC induced impairment may largely recover after a relatively short period of time.

Wenshuai Hou¹, Chandler Sours², Joseph JaJa³, and Rao Gullapalli^2
1ECE, University of Maryland, college park, Maryland, United States, ²Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, MD, United States, ³ECE, University of Maryland, MD, United States

mTBI is one of the most common neurological disorders. A subset of patients develops persistent cognitive deficits. Recent developments suggest that the dynamics of functional connectivity can reveal insightful information about anomalies in brain activities. Our data-driven approach focuses on the global brain functional network and leads to novel findings regarding the constantly changing neural connectivity. By analyzing the network properties measured after the dynamic sliding window analysis in addition to further differentiation of mTBI subjects based on long term recovery status, group difference (p < 0.05) were found between mTBI patients who fail to recover and healthy control subjects.

Sushanta Kumar Mishra¹, Subash Khushu¹, and Gangenahalli U Gurudutta^2
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, Delhi, India, ²Stem Cells Research Group, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, Delhi, India

Application of stem cells based therapeutic approaches in experimental models likely becomes a realistic alternative to conventional treatments. The mMSCs were labelled with D-Fe3O4 nanoparticles and fluorescent PKH26 dye. Transplantation of labelled stem cells in traumatic brain injury mice were monitored by 7T animal MRI and confocal microscopy. T2/T2* values were decreased significantly at the injury site on day-3, which indicated homing of the stem cells to the site of injury. Stem cells transplantation enhanced the therapeutic activity in TBI mice in terms of functional outcome like cognition, depression and locomotion.

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

We performed connectivity analysis of resting-state fMRI data obtained from Soldiers with PTSD and co-occurring post-concussion syndrome (PCS), along with matched military controls. We used static and dynamic functional connectivity measures. We tested the hypothesis that PTSD and PCS are associated with increased connectivity strength, but lower connectivity variance (calculated over time) compared to controls. The connectivity between striatum and hippocampus fit the above hypothesis, with additional burden in the comorbid group. This suggests that PTSD and PCS are associated with a hyper-connectivity state from which it is difficult to disengage, often observed with habit formation.

David C Zhu¹, Sally Nogle¹, Scarlett Doyle¹, Doozie Russell¹, Tracey Covassin¹, Randolph L Pearson¹, J Kevin DeMarco¹, and David I Kaufman^1
1Michigan State University, East Lansing, Michigan, United States

Recently the authors demonstrated a dynamic change of default-mode network functional connectivity with resting-state fMRI (rs-fMRI) on Days 1, 7 and 30 after concussion. In this pilot longitudinal study based on 11 concussion cases, we attempted to systematically isolate all potentially vulnerable networks among the 17 functional networks segmented by Yeo et al. from 1,000 young adults based on rs-fMRI. With node-based correlation analyses, we found six networks (DMN A and C, Salience/Ventral Attention A, Somatomotor B, Temporal-Parietal and Visual Peripheral) relatively more prone to the impact of concussion.

Wei Liu^1,2, Jennifer Pacheco^1,2, Cyrus Eierud^1,2, David Joy^1,3, Justin Senseney^1,2, Ping-Hong Yeh^1,2, Dominic Nathan^1,2, Elyssa Sham^1,2, John Ollinger^1,2, Terrence Oakes^1,2, and Gerard Riedy^1,2
1National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States, ²National Capital Neuroimaging Consortium, Bethesda, MD, United States, ³Center of Neuroscience and Regenerative Medicine, Bethesda, MD, United States

Cerebral perfusion of 204 chronic TBI patients from a military population was assessed using dynamic susceptibility contrast imaging. Mild and moderate TBI patients demonstrated unaltered regional cerebral blood flow (rCBF) in twelve subcortical ROIs compared to the 31 controls. Severe TBI patients demonstrated reduced rCBF in a couple regions. All three categories of the TBI patients demonstrated significantly increased asymmetric rCBF in the pallidum. However, the pallidum volume of the patients demonstrated similar right-left asymmetry compared to the controls. This increased asymmetric rCBF could be a compensatory mechanism to the reduced rCBF typically seen at the acute and subacute stage.

Michael Zeineh¹, David Douglas¹, Mansi Parekh¹, Eugene Wilson¹, Sherveen Parivash², Lex Mitchell³, Brian Boldt¹, Wei Scott Bian¹, Scott Anderson⁴, Andrew Hoffman⁵, Huy Scott Do¹, Gerald Scott Grant⁶, Jamshid Scott Ghajar⁶, and Greg Zaharchuk^1
1Radiology, Stanford University, Stanford, California, United States, ²Duke University, North Carolina, United States, ³Evans Army Community Hospital, Fort Carson, Colorado, United States, ⁴Sports Medicine, Stanford University, Stanford, California, United States, ⁵Internal Medine, Stanford University, Stanford, California, United States, ⁶Neurosurgery, Stanford University, Stanford, California, United States

Head injury is common in contact sports and can have long-term consequences. Brain perfusion may be reduced to regions of injury and can be measured noninvasively with MRI. We performed arterial spin labeling (ASL) on 47 football players, comparing with 21 control volleyball players. This demonstrated reduced perfusion in the hippocampi and thalami. The effect size of the reduced perfusion was much greater than for traditional volumetric analysis of the hippocampi. ASL may be a useful metric for evaluating mild traumatic brain injury in sports.

Ping-Hong Yeh¹, Fang-Cheng Yeh², John Ollinger³, Elyssa B. Sham³, Binquan Wang¹, David Joy¹, Justin Senseney³, Terrence R. Oakes³, and Gerard Riedy^3
1Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States, ²Department of Psychology & Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburg, Pennsylvania, United States, ³National Intrepid Center of Excellence, Bethesda, Maryland, United States

Relating clinical symptoms to brain structural changes is critical in understanding the sequalae following brain injury. Due to the essence of axonal loss in TBI, conventional tractography paradigm, requiring accurate tracks/connectome reconstruction in order to compare the group/individual difference, may miss lesions over the paths failed to reconstruct tracts. Using q space diffeomorphic reconstruction to identify affected pathways, diffusion MRI connectometry finds local difference in diffusion distribution,avoids any inaccuracy in fiber tracking. We applied this approach to relate self-reporting symptoms in military TBI patients to the affected white matter tracts.

Lian Li¹, Michael Chopp^1,2, Guangliang Ding¹, Changsheng Qu³, Siamak P Nejad-Davarani¹, Esmaeil Davoodi-Bojd¹, Qingjiang Li¹, Asim Mahmood³, and Quan Jiang^1,2
1Neurology, Henry Ford Hospital, Detroit, MI, United States, ²Physics, Oakland University, MI, United States, ³Neurosurgery, Henry Ford Hospital, Detroit, MI, United States

The capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA) and entropy, to dynamically detect the therapeutic effect of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) were investigated. Compared to delayed cell engraftment (1-week) after TBI, acute cell intervention (6-hour) promotes structural reorganization in the injured brain. While FA and entropy present the similar capacity to longitudinally detect the microstructural changes in the tissue region with predominant orientation of fiber tracts, entropy exhibits the sensitivity, superior to FA, in probing the structural alterations in the area with crossing fibers.

Xiao Wang¹, Xiao-hong Zhu¹, Afshin Divani², Yi Zhang¹, and Wei Chen^1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States,²Department of Neurology, University of Minnesota, Minnesota, United States

Blast-induced traumatic brain injury (bTBI) is of particular relevance to the military battles and urban terrorist attacks and has increasingly gained public attention. Proper preclinical bTBI models and noninvasive neuroimaging tools are crucial for early diagnosis, neuropathology progression monitor and treatment efficacy evaluation. We performed multiple MRI measures in a new bTBI rat model and found a highly synchronized and widely distributed rs-fMRI connectivity across almost the entire brain in some of the bTBI rats. This rs-fMRI characteristic is not sensitive to the presence of macroscopic lesion, baseline cerebral blood flow (CBF) and impaired cerebrovascular reactivity, but is persistent in the same rat for a long period of time. The abnormal connectivity pattern of lacking functional specificity might be related to the diminished brain functional segregation, disrupted neural excitation and/or inhibition and compensatory neuronal processes caused by the injury. The overall results reveal that the rs-fMRI can serve as a sensitive neuroimaging biomarker for noninvasively studying the underlying neuropathology mechanisms of the bTBI using a rat model, which should have a constructive impact for clinical translation in human TBI patients.

Ping-Hong Yeh¹, Jennifer Pacheco², Joseph Hennessey², Alex Kubli², Priya Santhanam², Terrence R. Oakes², Thomas Perkins³, Gerard Riedy², William W. Orrison⁴, and Lindell K. Weaver^5,6
1Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States, ²National Intrepid Center of Excellence, Bethesda, Maryland, United States, ³Philips Healthcare, Cleveland, Ohio, United States, ⁴Nevada Imaging Centers, Las Vegas, Nevada, United States, ⁵Department of Hyperbaric Medicine, Intermountain LDS Hospital and Intermountain Medical Center, Salt Lake City, Utah, United States, ⁶School of Medicine, University of Utah, Utah, United States

Simultaneous detection of the gray matter and white matter microstructural lesions is important in understanding the pathophysiologic mechanisms following brain injury. In this study, we applied multivariate analysis to assess gray matter and white matter microstructural changes in mild TBI (mTBI) patients with persistent post-concussive symptoms. Our findings support that multivariate analysis is superior to conventional univariate analysis in detecting aberrant white matter and gray matter changes in mTBI patients with post-concussive syndrome.

Brian Johnson¹, Semyon Slobounov², and Thomas Neuberger^2
1Penn State University, University Park, PA - Pennsylvania, United States, ²Penn State University, PA, United States

Although less severe, subconcuussive impacts happen more frequent and research suggests they may lead to neurological impairment later in life. Here we investigated the acute effects that subconcussive head trauma may have on the default mode network of the brain and whether or not this may be modulated by history of previous concussion. 24 current collegiate rugby players were recruited and underwent resting-state functional magnetic resonance imaging. Scanning took place before and after a full contact game. Increased connectivity was seen between pregame and postgame scans. Even an acute exposure to subconcussive impacts is enough to alter brain functional connectivity.

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

This study explored the use of MEMRI in mild TBI. MEMRI was hyperintense in the impact area at 1-3hrs, hypointense on day 2, and hypointense in the impact core with a hyperintense area surrounding the core on day 14. T2 MRI showed little contrast in the area below the impact at 1-3hrs, was hyperintense on day 2, pseudonormalized on day 7 and 14. MEMRI signal void in the area below the impact and the hyperintense area surrounding corresponded to tissue cavitation and reactive gliosis, respectively. MEMRI offers novel contrast for detecting mild TBI.

John M. Ollinger¹, PIng-Hong Yeh¹, David Joy¹, Terrence R Oakes¹, and Gerard Riedy^1
1NICoE, Walter Reed National Military Medical Center, Bethesda, Maryland, United States

John M Ollinger, Ping-Hong-Yeh, David Joy, Terrence R. Oakes, Gerard Riedy Although DTI parameters such as FA, AD, RD, and MD have demonstrated differences between patients with TBI and controls in group studies, they have not yet been applied in the clinic. The method proposed here uses tensor normalization, matched numbers of gradient vectors, and the Box-Cox transformation to derive t-statistics and Hotelling T2 maps which are thresholded to detect anomalous regions. The specificity and sensitivity are characterized by the probability of replication and the total number of detected regions as proxies. The probability of replication is shown be vary between 0.4 and .7 depending on the parameters chosen.

Lora Talley Watts¹, Michael O'Boyle¹, Robert Cole Boggs¹, Shiliang Huang¹, Justin Alexander Long¹, Qiang Shen¹, and Timothy Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Methylene blue (MB) has energy-enhancing and antioxidant properties. We have previously showed that a single intravenous MB dose reduces lesion volume, behavioral deficits in animal model of mild traumatic brain injury (TBI). This study evaluated the efficacy of chronic oral MB administration on mild TBI by longitudinally measuring lesion volume and functional outcome. We found that chronic oral MB treatment minimized lesion volume and functional deficits compared to vehicle-treated animals. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.

Yichu Liu^1,2, Lora Watts¹, Qiang Shen¹, Hemanth Manga^1,2, and Timothy Duong^1
1Research Imaging Center, University of Texas Health Science Center, San Antonio, Texas, United States, ²Biomedical Engineering, UT San Antonio, San Antonio, Texas, United States

The goal of this study was to use multiparametric MRI (T2, CBF, ADC, and FA) to longitudinally characterize the spatiotemporal dynamics during hyperacute and subacute mild traumatic brain injury (TBI) in mice. The impact was targeted to the left primary forelimb somatosensory cortex. Comparisons were made with functional assessment measured by the forelimb asymmetry test. Moreover, comparisons were also made with published rat mild TBI data under essentially

General Leung^1,2, Nathan W Churchill³, Anthony A Sheen¹, Shaylea Badovinac⁴, Marc A Settino³, Gerald R Moran⁵, Todd English⁵, Walter Montanera^1,2, Michael G Hutchison⁶, and Tom A Schweizer^3,7
1Medical Imaging, St. Michael's Hospital, Toronto, Ontario, Canada, ²Medical Imaging, University of Toronto, Toronto, Ontario, Canada, ³Neuroscience Research Program, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Ontario, Canada, ⁴University of Toronto, Ontario, Canada, ⁵Siemens Canada Ltd, Ontario, Canada, ⁶Concussion Program, Faculty of Kinesiology and Physical Education, University of Toronto, Ontario, Canada, ⁷Faculty of Medicine, Neurosurgery, University of Toronto, Ontario, Canada

Approximately 20% of mild traumatic brain injury (mTBI) are sports related concussive injuries, of which nearly half receive no medical attention. During this acute post traumatic period, the brain appears to be more susceptible to injury and return to play (RTP) guidelines are made further more difficult by studies showing metabolic changes up to 30 days after a concussive event. We image 26 athletes, 7 acutely post concussion and show an acute reduction in NAA/Cho ratio that appears to normalize on RTP.

Sohae Chung^1,2, Els Fieremans^1,2, Jelle Veraart^1,2, Dmitry S. Novikov^1,2, Jacqueline Smith^1,2, Steven R. Flanagan³, and Yvonne W. Lui^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, United States, ³Department of Rehabilitation Medicine, New York University Langone Medical Center, New York, NY, United States

Mild traumatic brain injury (mTBI) is a growing public health problem; however, overall sensitivity to white matter (WM) injury and understanding of the underlying pathophysiology is limited. Here, we investigate WM abnormalities in mTBI by using WM diffusion metrics, as derived from DKI with a two-compartment model. Using TBSS and ROI analyses, we demonstrate that there are several metrics that are sensitive to injury after mTBI, suggesting that increased restrictions along the axons, both inside and outside, such as possibly axonal beading, could occur acutely after injury. This provides unique insight into the underlying mechanisms of WM alterations after mTBI.

Nathan Churchill¹, Michael G Hutchison², Doug Richards², Shaylea Badovinac³, Marc A Settino¹, General Leung^4,5, Gerald R Moran⁶, Todd English⁶, Anthony Sheen⁷, and Tom A Schweizer^8,9
1Neuroscience Research Program, Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Ontario, Canada, ²Concussion Program, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada, ³University of Toronto, Ontario, Canada, ⁴Medical Imaging, University of Toronto, Toronto, Ontario, Canada, ⁵Keenan Research Centre, St Michael's Hospital, Ontario, Canada, ⁶Siemens Canada Ltd, Ontario, Canada,⁷Medical Imaging, St. Michael's Hospital, Ontario, Canada, ⁸Neuroscience Research Program, Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Ontario, Canada, ⁹Faculty of Medicine (Neurosurgery), University of Toronto, Ontario, Canada

Traumatic brain injury (TBI) presents a major health issue, as even mild TBI can lead to significant impairments. Heart rate variability (HRV) is often used as a clinical measure of mTBI, indicating autonomic dysregulation. Recent studies have also demonstrated that neuronal variability at different time-scales is related to mTBI. We propose a novel approach of combining HRV with the neurovascular measures of BOLD fMRI, to characterize the impact of mTBI. We use multi-scale wavelet decomposition and measure the coupling between BOLD signal and HRV across time-scales using Partial Least Squares, which demonstrates significant differences between mTBI and control groups.

Seul Lee^1,2, Jonathan R Polimeni³, Thomas Witzel³, Collin M Price⁴, Michael D Greicius⁴, Brian L Edlow^3,5, and Jennifer A McNab^2
1Department of Electrical Engineering, Stanford University, Stanford, CA, United States, ²Department of Radiology, Stanford University, Stanford, CA, United States, ³Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United States, ⁴Department of Neurology, Stanford University, CA, United States, ⁵Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MA, United States

In this study, we investigate the effect of seed-placement on the ability to identify reorganized brain networks using resting-state FMRI in a patient with hemorrhagic traumatic axonal injury lesions.

Ikbeom Jang¹, Il Yong Chun¹, Larry J. Leverenz², Eric A. Nauman^3,4, and Thomas M. Talavage^1,4
1School of Electrical & Computer Engineering, Purdue Universisty, West Lafayatte, Indiana, United States, ²Department of Health & Kinesiology, Purdue Universisty, Indiana, United States, ³School of Mechanical Engineering, Purdue Universisty, Indiana, United States, ⁴Weldon School of Biomedical Engineering, Purdue Universisty, Indiana, United States

Using diffusion-weighted MR imaging, a single subject-based approach is proposed here to detect athletes exhibiting longitudinal deviations in fractional anisotropy (FA) as observed by paired tract-based spatial statistics (TBSS). High-school aged male football and female soccer athletes were scanned longitudinally three times during the course of a competition season, during which they experienced multiple collisions to the head or whiplash-like acceleration events. Significant increases in FA were observed in the second half of the season, relative to the pre-season measures, for most asymptomatic soccer players.

Yang Wang^1,2, Benedicte Marechal^3,4, Dawn Neumann², Alexis Roche^3,4, John D West², Brenna C McDonald², Michelle A Keiski², Dori J Smith², Andrew J Saykin², and Gunnar Kruger^3,4
1Medical College of Wisconsin, Milwaukee, WI, United States, ²Indiana University School of Medicine, Indianapolis, IN, United States, ³Siemens Healthcare IM BM PI & Department of Radiology CHUV, Lausanne, Switzerland, ⁴LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Identification of structural abnormalities in chronic traumatic brain injury (TBI) remains challenging because the brain often appears quite normal on conventional CT and MRI scans. Using an automatic volume-based morphometry toolbox, we have evaluated atrophy in chronic moderate and severe TBI that is associated with severity of cognitive deficit. Our results suggest the usefulness of this toolbox in clinical settings for fast volumetric analysis without complex post-processing steps.

Ramtilak Gattu¹, Robert Welch², Brian Oneil³, Anamika Chaudhary¹, Ewart Mark Haacke¹, and Zhifeng Kou^1
1Radiology, wayne state university, Detroit, Michigan, United States, ²Emergency Medicine, wayne state university, Detroit, Michigan, United States,³Emergency Medicine, wayne state university, Michigan, United States

A regional and lesion load analysis of different DTI parametric maps has been investigated; we have found that when regional analysis fails to be sensitive enough in distinguishing between the groups, lesion load can serve as surrogate marker that helps in diagnosis of neurocognitive or neurological deficits in the TBI population. A strong positive correlation also have been associated between decreased FA lesion load and increased radial diffusivity, decreased axial diffusivity, increased apparent diffusion coefficient and increased trace lesion load. These different associations might give us better understanding behind the strong driving forces in predicting the FA white matter changes.

Naeim Bahrami¹, Harish Sharma¹, Elizabeth Davenport¹, Jillian Urban², Joel Stitzel², Christopher Whitlow¹, and Joseph Maldjian^1
1Wake Forest School of Medicine, NC, United States, ²Wake forest school of Biomedical Engineering, NC, United States

The purpose of this study was to investigate the individual effects of linear and rotational accelerations on the white matter changes in high school football players using DTI

Spinal Cord & Plexus

Wednesday 3 June 2015

Rebecca Sara Samson¹, Carolina Kachramanoglou¹, David Choi², Antoine Lutti³, David L Thomas⁴, Nikolaus Weiskopf³, Olga Ciccarelli^5,6, and Claudia A M Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Spinal Repair Unit, UCL Institute of Neurology, London, England, United Kingdom, ³Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, England, United Kingdom, ⁴5Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, England, United Kingdom, ⁵NMR Research Unit, Department of Brain Repair and Rehabilitation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ⁶6NIHR UCL/UCLH Biomedical Research Centre (BRC), London, England, United Kingdom

Brachial plexus avulsion (BPA) may lead to paralysis and anaesthetic of the corresponding arm. Re-implantation of avulsed ventral roots is an effective surgical technique that leads to improved motor recovery. The development of quantitative MRI methods to assess spinal cord tissue structure following BPA may provide sensitive non-invasive markers for therapy monitoring. We aimed to assess whether multi-parameter mapping of the upper cervical cord (i.e., above the site of injury) detects pathological changes in patients with BPA who have received re-implantation, when compared with healthy subjects. In patients, the relationship between measured quantitative parameters and clinical outcome measures is explored.

Benjamin De Leener¹, Augustin Roux¹, Manuel Taso^2,3, Virginie Callot^2,3, and Julien Cohen-Adad^1,4
1Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, Quebec, Canada, ²Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France,³AP-HM, Pôle d’imagerie médicale, Hopital de la Timone, CEMEREM, Marseille, France, ⁴Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, Quebec, Canada

We propose a novel method for segmenting the spinal cord gray and white matter using atlas-based deformation. The main steps are: (i) registration of the MNI-Poly-AMU template on a T2*-weighted image, (ii) deformation of the gray matter probabilistic atlas from the template on T2*-weighted images using SyN transformation (ANTs) and (iii) applying the resulting warping field on the white matter atlas. Results demonstrate accurate gray matter segmentation when compared to manual segmentation. An application of the smooth deformation-based segmentation is the accurate parcellation of the atlas of white matter tracts for quantifying multi-parametric MRI metrics.

Samantha By^1,2, Alex K. Smith^1,2, Lindsey M. Dethrage², Adrienne N. Dula^2,3, Siddharma Pawate⁴, and Seth A. Smith^2,3
1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ²Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ³Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Department of Neurology, Vanderbilt University, Nashville, TN, United States

Amide proton transfer (APT) CEST has the potential to probe metabolic composition of spinal cord lesions in diseases such as multiple sclerosis (MS). Due to the inherent challenges of spinal cord imaging, however, there are few reports of APT CEST in the spinal cord, making translation to diseased cohorts difficult. We investigate the application of a pulsed CEST acquisition with a Lorentzian difference analysis in healthy controls and a MS patient with known spinal cord lesions. Initial results demonstrate profound tissue changes marked by increased APT concentrations at the lesion sites in the MS patient relative to healthy controls.

Manuel Taso^1,2, Olivier M. Girard^3,4, Guillaume Duhamel^3,4, Thorsten Feiweier⁵, Pierre-Jean Arnoux², Maxime Guye^3,4, Jean-Philippe Ranjeva^3,4, Kathia Chaumoitre⁶, Pierre-Hugues Roche⁷, and Virginie Callot^3,4
1CRMBM-CEMEREM UMR 7339, Aix-Marseille Université, CNRS, Marseille, France, ²LBA UMR T 24, Aix-Marseille Université, IFSTTAR, Marseille, France, ³CRMBM UMR 7339, Aix-Marseille Université, CNRS, Marseille, France, ⁴CEMEREM, Pole d'imagerie médicale, Hopital la Timone, AP-HM, Marseille, France, ⁵Siemens AG, Healthcare, Erlangen, Germany, ⁶Service de radiologie, Hopital Nord, Pole d'imagerie médicale, AP-HM, Marseille, France, ⁷Service de Neurochirurgie,Trauma Center, Hopital Nord, AP-HM, Marseille, France

Cervical myelopathy diagnosis and management in clinical practice still lacks of objective markers of potential surgery outcome. Therefore, we applied a multimodal MRI protocol, combining DTI (known to be more predictive of surgical outcome than the sole presence of T2 hyperintensity) and inhomogeneous magnetization transfer (ihMT, myelin-specific technique) to 2 patients before and 3 months after decompressive surgery. We observed both metrics evolution after surgery and neurological function evolution to see whether this multimodal protocol could help in understanding the evolutive pattern of the disease after surgery. Longitudinal follow-up until 1year post-surgery will help in answering the raised question.

Oscar San Emeterio Nateras¹, Fang Yu², Eric R Muir^3,4, Carlos Bazan III², Crystal G Franklin⁴, Wei Li^3,4, Jack L Lancaster^2,4, Jinqi Li^2,4, and Timothy Q Duong^3,4
1Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, United States, ²Radiology, University of Health Science Center at San Antonio, Texas, United States, ³Ophthalmology, University of Health Science Center at San Antonio, Texas, United States, ⁴Research Imaging Institute, San Antonio, Texas, United States

This study demonstrates a novel rsfMRI application to investigate the spinal cord. We found extensive functional networks in the spinal C1-C4, and they included some unilateral, bilateral and top-down functional connectivity. Future studies will improve spatial resolution, validate the functional networks and to map connectivity of the entire spinal cord to the brain.

J. Cohen-Adad^1,2, S. Lévy¹, and B. Avants^3
1Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada, ²Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, QC, Canada, ³PENN Image Computing & Science Lab, Dept of Radiology, UPENN, Philadelphia, PA, United States

Within-subject registration of spinal cord data is a difficult problem because the articulated nature of the spine can produce non-rigid deformations. To address this, researchers have introduced slice-by-slice registration using only translations within the axial plane. Although more accurate than volume-based transformations, this approach lacks robustness because each slice is treated independently from the others. Here we introduce a novel method (SliceReg) that estimates slice-by-slice transformations with polynomial regularization along the spinal cord axis. SliceReg has been validated in 25 datasets and shows higher accuracy than volume-based transformations and benefit from regularization in comparison with slice-by-slice techniques.

Sean Foxley¹, Jeroen Mollink¹, Olaf Ansorge², Connor Scott², Saad Jbabdi¹, Richard Yates², Gabriele De Luca², and Karla Miller^1
1FMRIB Centre, University of Oxford, Oxford, OXON, United Kingdom, ²Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OXON, United Kingdom

Post-mortem imaging has begun to attract interest as a method for anatomical investigation that can achieve higher resolution than in-vivo imaging and be directly compared against histological gold standards. In this work we investigate collecting diffusion weighted data of whole post-mortem human spinal cord at 7T using diffusion-weighted SSFP. Tractography and fibre population estimate results demonstrate that methodological and procedural developments produce high fidelity data with coherent primary diffusion direction estimates and significant secondary collateral fibre estimates. Correlation with PLI data demonstrates the potential for validating collateral fibre orientations with MR data.

Andrew C.H. Yung¹, Peggy Assinck², Di Leo Wu³, Jie Liu², Shaalee Dworski⁴, Freda Miller⁴, Wolfram Tetzlaff^2,5, and Piotr Kozlowski^1,2
1UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ²ICORD, Vancouver, BC, Canada, ³Physics, University of British Columbia, Vancouver, BC, Canada, ⁴Hospital for Sick Children, Toronto, ON, Canada, ⁵Zoology, University of British Columbia, Vancouver, BC, Canada

Using an image registration approach, we assess the spatial correlation between ex vivo myelin water fraction (MWF) and transverse diffusivity (Dtrans) to histology-derived myelin area fraction (EC+P0 area fraction) in a contusion rat model of spinal cord injury, with and without treatment with SKP-SC cell therapy. Pearson coefficients for EC+P0 area fraction vs. MWF and Dtrans were 0.69 and -0.49, respectively. MWF and EC+P0 area fraction both showed a higher myelin content in the SKP-SC treated group as compared to cords injected with media alone, whereas Dtrans did not detect any statistically significant differences between groups.

Aurélien Massire^1,2, Pierre-Henri Rolland³, Maxime Guye^1,2, and Virginie Callot^1,2
1CRMBM UMR 7339 CNRS, Aix-Marseille Université, Marseille, France, ²CEMEREM, Hôpital de la Timone, Pôle d’imagerie médicale, AP-HM, Marseille, France,³Experimental Interventional Imaging Laboratory, Aix-Marseille Université, Marseille, France

This work provides preliminary diffusion tensor imaging (DTI) results on an ex vivo porcine spinal cord on a whole-body 7 Tesla. A readout-segmented echo-planar imaging sequence using parallel imaging was optimized to minimize magnetic susceptibility-induced image distortions. As severe distortions occurred, an additional post-processing correction tool was subsequently run on two independent data sets acquired with opposed phase-encode directions. Successful and robust distortion corrections were observed along the ten slices, leading the way to in vivo human spinal cord DTI.

Adrienne Dula¹, Siddharama Pawate¹, Lindsey M Dethrage¹, Benjamin N Conrad¹, Robert L Barry¹, and Seth A Smith^1
1Vanderbilt University, Nashville, Tennessee, United States

Optimal CEST saturation parameters found via simulation were implemented for CEST MRI in ten healthy controls and ten MS patients and results were examined using traditional asymmetry analysis and Lorentzian fit method. Distinct spectral features for all tissue types studied were found both up- and down-field from the water resonance. The z-spectra in healthy subjects had the expected z-spectra shape with CEST effects apparent from 2.0 ppm – 4.5 ppm while the z-spectra from MS patients demonstrated deviations from this expected, normal shape indicating this method’s sensitivity to known pathology as well as those tissues appearing normal on conventional MRI.

Kayla Ryan^1,2, Sandy Goncalves^1,2, Izabela Aleksanderek^1,2, Robert Bartha^1,2, and Neil Duggal^1,3
1Medical Biophysics, Western University, London, Ontario, Canada, ²Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, ³Clinical Neurological Sciences, University Hospital, London, Ontario, Canada

Cervical spondylotic myelopathy is the most common degenerative disease after the age of 55. The cervical spinal cord becomes impinged, causing motor and sensory dysfunction and gait abnormalities. When there is damage to the brain or spinal cord, cortical plasticity has been shown to occur as a compensatory technique to maintain function. Ipsilateral motor areas have been shown to be recruited when cortical demand exceeds cortical output. The purpose of this study was to characterize and quantify the activation patterns of the ipsilateral motor areas and its role in functional recovery.

Wei Liu¹, Himanshu Bhat², Julien Cohen-Adad³, Kawin Setsompop⁴, Dingxin Wang⁵, Thomas Beck⁶, Stephen F. Cauley⁴, Kun Zhou¹, and David A. Porter^7
1Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong, China, ²Siemens Medical Solutions USA, Inc., Charlestown, MA, United States,³Department of Electrical Engineering, Institute of Biomedical Engineering, Ecole Polytechnique de Montreal, Montreal, QC, Canada, ⁴A.A. Martinos Center for Biomedical Imaging, Dept. of Radiology, MGH, Charlestown, MA, United States, ⁵Siemens Medical Solutions USA, Inc., Minneapolis, MN, United States, ⁶MR Application Development, Siemens Healthcare, Erlangen, Germany, ⁷Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany

Readout-segmented EPI (rs-EPI) is an established clinical technique for acquiring DW images with reduced distortion and T2*-related blurring, which is therefore particularly well-suited to acquire high-quality DW data from the whole brain and cervical spine. However, the acquisition time increases with the number of readout segments. In this study, we demonstrate how the blipped-CAIPIRINHA simultaneous multi-slice technique can be used with rs-EPI to provide a unique method for performing rapid tractography studies of the brain and spinal cord with low distortion and a large anatomical coverage, whilst preserving data quality for tractography studies.

J. Touati¹, M. Taso^2,3, V. Fonov⁴, A. Le Troter^2,3, B. De Leener¹, D.L. Collins⁴, V. Callot^2,3, and Julien Cohen-Adad^1,5
1Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada, ²CRMBM UMR 7339, Aix- Marseille Université, CNRS, Marseille, France,³CEMEREM, Hopital de la Timone, Pôle d’imagerie médicale, AP-HM, Marseille, France, ⁴Montreal Neurological Institute, McGill University, Montreal, QC, Canada,⁵Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, QC, Canada

xx

Benjamin N Conrad¹, Bailey D Lyttle², Siddharama Pawate³, Robert L Barry^1,4, Bennett A Landman^1,5, and Seth A Smith^1,4
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Neuroscience, Vanderbilt University, Nashville, TN, United States,³Neurology, Vanderbilt University, Nashville, TN, United States, ⁴Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Electrical Engineering, Vanderbilt University, Nashville, TN, United States

Spinal cord atrophy is a clinical symptom associated with many diseases, including multiple sclerosis. The most commonly reported measure of atrophy involves estimation of the cross sectional area (CSA) of the cord from anatomical MRI. Advances in image acquisition and segmentation methods are converging to allow for reliable, fully automated techniques for assessing CSA. The current analysis validates a recently developed automatic labeling scheme using T2*-weighted images by comparing estimated CSA in MS patients and healthy controls versus a standard, semi-automated estimation using T1-weighted images.

Benjamin De Leener¹, Augustin Roux¹, Julien Touati¹, Simon Levy¹, Manuel Taso^2,3, Vladimir Fonov⁴, D. Louis Collins⁴, Virginie Callot^2,3, and Julien Cohen-Adad^1,5
1Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, Quebec, Canada, ²CRMBM UMR 7339, Aix-Marseille Université, CNRS, Marseille, France,³CEMEREM, Hopital de la Timone, Pôle d’imagerie médicale, AP-HM, Marseille, France, ⁴Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, ⁵Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, Quebec, Canada

The Spinal Cord Toolbox is an open-source software package for processing and analysis of multi-parametric MRI data of the spinal cord. Main features are automatic spinal cord segmentation (PropSeg), motion correction based on slice-wise regularized registration, web-based interface and template-based registration enabling metric extraction (e.g., cross-sectional area, fractional anisotropy, mean diffusivity, MTR) for any vertebral and spinal level and for specific white matter tracts (e.g., corticospinal, cuneatus). By providing the first semi-automatic framework for registering MR images on a common template, the Spinal Cord Toolbox opens the door to large-group and multi-center studies of spinal cord MRI data.

Andrew C.H. Yung¹, Stephen Mattucci², Barry Bohnet¹, Jie Liu², Wolfram Tetzlaff², Piotr Kozlowski¹, and Thomas Oxland^2
1UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ²ICORD, Vancouver, BC, Canada

We assessed the ability of ex vivo longitudinal diffusivity (Dlong) to differentiate between two injury mechanisms of rat SCI (standard contusion model and a novel dislocation model) at various time points after injury (3 hours, 24 hours, 7 days). Regional white matter Dlong averages (dorsal, lateral, ventral) were compared along the rostrocaudal extent of the cord. The observed spatial patterns in Dlong were distinctly different between the injury models; in particular, the dislocation model showed a greater reduction in Dlong in the lateral white matter as compared to the dorsal white matter Dlong, and vice-versa for the contusion model.

Mitsuharu Miyoshi¹, Shigeo Okuda², Masahiro Jinzaki², Atsushi Nozaki¹, and Hiroyuki Kabasawa^1
1Global MR Application and Workflow, GE Healthcare Japan, Hino, Tokyo, Japan, ²2. Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan

MR neurography is an important non-invasive method to know the 3D structure of brachial plexus. 3D T2 Fast Spin Echo with STIR (Short Tau Inversion Recovery) is often used for homogenous fat saturation. STIR and Two Point Dixon were compared in this study. Nerve signal could be separated from fat and background signals in both methods. Noise is lower in Two Point Dixon method and vessel connectivity was improved.

Anand Kumar Venkatachari¹, Suchandrima Banerjee², Mitsuharu Miyoshi³, Ajit Shankaranarayanan², William Dillon⁴, Sharmila Majumdar¹, and Christopher Hess^4
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, ²Global Applied Science Laboratory, GE Healthcare, Menlo Park, California, United States, ³Global Applied Science Laboratory, GE Healthcare, Hino, Japan, ⁴Neuroradiology, University of California San Francisco, San Francisco, California, United States

Magnetic Resonance Neurography (MRN) provides useful information regarding nerve compression, displacement, swelling and injury. While fat-suppressed T2 weighted acquisition depicts the nerve elements in brachial plexus, lumbar plexus and sciatic nerves in the pelvis, significant technical challenges remain with respect to achieving satisfactory fat and vascular suppression, high spatial resolution and short imaging times. Most existing clinical protocols rely upon fat-suppressed 2D fast spin echo acquisition in three planes, a practice that results in long acquisition times. We have developed a reduced field-of-view, volumetric FSE sequence that permits high-resolution MRN in a short acquisition time, with isotropic acquisition and excellent fat and vascular flow suppression.

Robert L Barry^1,2, Seth A Smith^1,2, and John C Gore^1,2
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States

Spinal cord functional magnetic resonance imaging studies have typically used task-based paradigms to elicit activation, but a recent resting state study at 7 Tesla demonstrated the existence of resting state networks in the human spinal cord. In this abstract we translate the acquisition, preprocessing, and analysis methods developed at 7 Tesla down to 3 Tesla. Our results suggest that with a longer run length these spinal cord networks may similarly be detected at 3 Tesla, and therefore may have immediate and widespread clinical applicability for studying diseases of the central nervous system.

Moreno Pasin¹, Marios C Yiannakas¹, Ahmed T Toosy², and Claudia A M Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre​, UCL Institute of Neurology, London, England, United Kingdom,²Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, England, United Kingdom

Investigating spinal cord function and white matter microstructure using MRI implies coping with several technical issues. This study uses a protocol matching functional and structural spinal images and investigates correlations between functional and structural parameters obtained in 10 healthy controls undertaking a sensory task delivered on both left and right hand separately. Signal enhancement and lateralization index(LI) are reported. Fractional anisotropy(FA), radial diffusivity(RD), axial diffusivity(AD) and mean diffusivity(MD) were calculated in ROIs drawn on: whole cord, right hemisphere, left hemisphere and posterior column white matter. No correlation was found between LI and the FA, MD, RD and AD values for any ROIs.

Evan I-Wen Chen^1,2, Jie Liu², Vanessa Wiggermann¹, Andrew Yung¹, Alexander Rauscher^1,3, and Piotr Kozlowski^1,3
1MRI Research Center, Vancouver, BC, Canada, ²International Collaboration On Repair Discoveries, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada

Gold standard histology is used to characterize degeneration pathology in an injury model that generates white matter injury in CNS (spinal cord). We compare DTI, MWF, and frequency shift mapping to evaluate effectiveness, advantages, and disadvantages of each. Frequency shift mapping is sensitive relative to changes to histology, and has advantages of higher spatial resolution, higher SNR, and lower scan times compared to MWF and DTI. Frequency shift mapping can benefit from structural information from DTI to better separate the effects of axonal or myelin damage to improve the accuracy of MRI of spinal cord transection injury.

Masaaki Hori^1,2, Ryuji Nojiri², Katsutoshi Murata³, Yuichi Suzuki⁴, Koji Kamagata¹, Mariko Yoshida¹, Kouhei Tsuruta^1,5, Keiichi Ishigame², and Shigeki Aoki^1
1Radiology, Juntendo University School of Medicine, Tokyo, Japan, ²Tokyo Medical Clinic, Tokyo, Japan, ³Siemens Japan K.K., Tokyo, Japan, ⁴Radiology, The University of Tokyo Hospital, Tokyo, Japan, ⁵Department of Health Science, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan

We investigate the effect of multi-band reduction factor (MBf) on Neurite orientation dispersion and density imaging (NODDI) metrics and to compare less number of motion probing gradient (MPG) axes 2-shell protocol NODDI metrics with 2-shell 30 MPG protocol in the cervical spinal cord white matter in vivo. Between Mbf 2 and 3 data, there were significant differences in ICVF and IVF. With increasing of number of measurements, improved agreement was observed between 30 MPG data metrics and less number MPG data. Therefore, we recommend that more than 24 MPG axes and MBf of 2 for spinal cord NODDI with multiband-EPI.

Alexander Beckett^1,2, Liyong Chen^1,2, Ajay Verma³, and David A Feinberg^1,2
1Helens Wills Neuroscience Institute, University of California, Berkeley, CA, United States, ²Advanced MRI Technology, Sebastopol, CA, United States, ³Biogen Idec, MA, United States

Previous research has indicated that respiratory modulations can influence changes in the velocity of CSF flow in the brain and spine. We use simultaneous multi-slice EPI to measure changes in CSF velocity in multiple levels of the spine simultaneously, and show modulations in velocity at the same frequency as respiration. Respiratory modulations are also seen in non-spine (kidney) ROIs, with a phase opposite to that of the spinal modulations.

Yunlong Song¹, Lihua Sun¹, Guangnan Quan², and Lizhi Xie^2
1Department of CT & MRI, Air Force General Hospital, Beijing, Beijing, China, ²GE Healthcare China, Beijing, China

To find the difference between normal lumbosacral nerve roots and lumbar disc herniation nerve roots by comparing the IDEL and FIESTA technologies.