Jiri M.G. van Bergen¹, Xu Li², Frances C. Quevenco¹, Anton F. Gietl¹, Valerie Treyer^1,3, Rafael Meyer¹, Sandra E. Leh¹, Alfred Buck³, Roger Nitsch¹, Peter C.M. van Zijl², Christoph Hock¹, and Paul G. Unschuld^1
1Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland, ²F.M. Kirby center for Functional Brain Imaging, Kennedy Krieger Institute and Johns Hopkins School of Medicine, Baltimore, MD, United States, ³Division of Nuclear Medicine, University of Zurich, Zurich, Switzerland

We investigated “super-agers” (a minority of elderly subjects that display significantly higher cognitive performance levels) for the interaction of Aβ-plaque burden and iron load, using Quantitative Susceptibility Mapping and simultaneous 18F-Flutametamol measures in the PET-MR. We found significant increased iron load in the putamen and caudate nucleus of subjects with a high Aβ-plaque burden, but no regional correlations between the two markers in gray matter. This suggests that while super-agers are affected by common age-related brain pathologies, such as cortical Aβ-plaque burden and increased striatal iron load, these might exert less neurotoxic damage.

Geon-Ho Jahng¹, Janghoon Oh¹, Hyug-Gi Kim¹, Do-Wan Lee², Chanhee Lee¹, Hak Young Rhee³, Chang-Woo Ryu¹, Wonchul Shin³, Jong-Woo Paik⁴, Kyung Mi Lee⁵, Soonchan Park¹, Bo-Young Choe², and Dal-Mo Yang^1
1Department of Radiology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Korea, Republic of, ²Department of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea, Republic of, ³Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Korea, Republic of, ⁴Department of Mental Health, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea, Republic of, ⁵Department of Radiology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea, Republic of

To investigate the metabolite changes in subjects with AD, MCI, and cognitively normal (CN) elderly during a memory task using dynamic MRS at a 3T MRI system, we included 95 subjects who included: 23 young normal control (YC), 24 cognitively normal (CN) elderly, 24 aMCI, and 24 mild and probable AD. The functional MRS data were measured during the face-name association task with the stimulation paradigm of fixation, novel, and repeat conditions. The fMRS data were analyzed using the LCModel software. Glx was altered during the stimulation conditions, which can be used in neuronal dysfunction for a patient with dementia.

Jun Hua^1,2, SeungWook Lee³, Nicholas I.S. Blair³, Michael Wyss⁴, Simon J Schreiner⁵, Stefanie C Steininger⁵, Sandra Leh⁵, Roger Nitsch⁵, Klaas P Pruessmann⁴, Peter C.M. van Zijl^1,2, Marilyn Albert ⁶, Christoph Hock⁵, and Paul G Unschuld^5
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²Neurosection, Div. of MRI Research, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ⁴Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland, ⁵Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich and ETH Zürich, Zürich, Switzerland, ⁶Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Cerebrovascular dysfunction has been associated with mild-cognitive-impairment (MCI) and Alzheimer’s Disease (AD). Recent animal studies in aging show that abnormalities in pial arteries and arterioles start before other blood vessels and blood flow are affected. We show that cerebral-blood-volume of pial arteries and arterioles (CBVa), measured with the inflow-based vascular-space-occupancy (iVASO) MRI, is significantly altered in various brain regions in MCI patients compared to healthy elderly controls. CBVa in the orbitofrontal cortex significantly correlated with APOE-e4 carrier-status, the major genetic risk factor for sporadic AD. Our results suggest CBVa as a potential biomarker at an early stage of the disease.

Hanzhang Lu¹, Min Sheng², Peiying Liu¹, Harshan Ravi¹, Shin-Lei Peng¹, Ramon Diaz-Arrastia³, Michael D. Devous Sr.⁴, and Kyle B. Womack^5
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ³Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ⁴Avid Radiopharmaceuticals, Inc., Philadelphia, PA, United States, ⁵Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Alzheimer’s disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD. Our study applied several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2) and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in AD patients. Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD.

Eva-Maria Ratai^1,2, Kimberly A. Stephens^1,2, Alison E. Goldblatt^1,2, Jean-Philippe Coutu^1,2, Ciprian Catana^1,2, Diana Rosas^2,3, and David Salat^1,2
1Radiology, Massachusetts General Hospital, Boston, MA, United States, ²A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Neurology, Massachusetts General Hospital, Boston, MA, United States

The purpose of this study was to find associations between metabolites measures by MRS and glucose metabolism using FDG PET and cerebral blood flow (CBF) measured by ASL MRI in the assessment of Alzheimer’s Disease.  Our study shows an association between increased myo-inositol, a marker of glial inflammation, and hypo-metabolism measured by FDG as well hypo-perfusion measured by ASL.  Liner regression analysis revealed that creatine, a marker of altered energy metabolism positively correlated with increased glucose uptake by FDG PET. Increased levels of glutamate+glutamine (contributing to excitotoxicity) were related to decreased metabolic activity by PET and decreased CBF.  

Elisa Canu¹, Federica Agosta¹, Silvia Basaia¹, Alessandro Meani¹, Sebastiano Galantucci¹, Francesca Caso¹, Giuseppe Magnani², Roberto Santangelo², Monica Falautano², Giancarlo Comi², Andrea Falini³, and Massimo Filippi^1,2
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ³Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

This is a graph analysis study applying a new parcellation approach, which combines the need for equal sized nodes with respecting brain anatomy, on resting state fMRI data from a population of 247 patients with neurodegenerative cognitive impairment (early [EO] and late onset [LO] Alzheimer’s disease (AD), behavioural frontotemporal dementia [bvFTD], mild cognitive impairment [MCI]) and 86 controls. Compared to other groups, AD patients showed disrupted global network connectivity, while MCI had specific regional changes, suggesting that graph-analysis is promising to detect early features of neurodegeneration. Global and regional graph network properties were able to distinguish EOAD and bvFTD. 

Xinyu Zhao¹, D Rangaprakash¹, D Narayana Dutt², and Gopikrishna Deshpande^1,3,4
1Electrical and Computer Engineering, AU MRI Research Center, Auburn, AL, United States, ²Medical Electronics, Dayananda Sagar College of Engineering, Bangalore, India, ³Psychology, Auburn University, Auburn, AL, United States, ⁴Alabama Advanced Imaging Consortium, Auburn University and University of Alabama Birmingham, Auburn, AL, United States

Many brain-based disorders are traditionally diagnosed based on clinical interviews and behavioral assessments. Using Alzheimer’s spectrum (i.e. mild cognitive impairment [MCI] and Alzheimer’s disease [AD]) as a test case, we investigated whether clinical diagnostic grouping is grounded in underlying neurobiological and phenotypic clusters. In order to do so, three unsupervised learning methods were applied on resting-state fMRI connectivity measures obtained from subjects with MCI and AD. High similarity was achieved between connectivity and phenotypic clusters while similarity was low with clinical diagnosis. It shows that neurobiological and phenotypic markers could be used to improve the precision of clinical diagnosis.

Holly E Holmes¹, Nick Powell², James M O'Callaghan¹, Jack A Wells¹, Ian F Harrison¹, Da Ma², Ozama Ismail¹, Victor LJ Tybulewicz³, Frances Wiseman⁴, Sebastian Ourselin², Elizabeth M Fisher⁴, and Mark F Lythgoe^1
1Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, ²Centre for Medical Image Computing, University College London, London, United Kingdom, ³National Institite for Medical Research, London, United Kingdom, ⁴Institute of Neurology, University College London, London, United Kingdom

Magnetic resonance angiography (MRA) is an established MRI technique for visualising the cerebral vasculature. Interpretation of MR angiograms is often reliant on visual inspection of the data;¹however, it is possible to misinterpret flow artefacts (e.g.  signal voids) as vascular alterations.² In this work, we have used a novel combination of MRA and advanced registration as well as statistical algorithms to explore vascular alterations in the Tc1 mouse model of Down’s syndrome. We identified operator-independent local disturbances in the vascular architecture, which supports previous work in this mouse model as well as observations in the wider DS population. 

Qing Wang^1,2, Yong Wang^1,3,4, Joshua S Shimony¹, Anne M Fagan^2,5, John C Morris^5,6, and Tammie L.S. Benzinger^1,6,7
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States, ²Knight Alzheimer's Disease Research Center, St. Louis, MO, United States, ³Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO, United States, ⁴Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States, ⁵Neurology, Washington University in St. Louis, St. Louis, MO, United States, ⁶Knight Alzheimer’s Disease Research Center, St. Louis, MO, United States, ⁷Neurosurgery, Washington University in St. Louis, St. Louis, MO, United States

Robust neuroimaging biomarker sensitive to the early white matter abnormalities could provide novel insights into the pathogenesis of Alzheimer’s disease (AD), and serve as surrogate measures for disease progression. We demonstrated that novel DBSI white matter abnormality biomarkers strongly correlate with invasive CSF measures of neuronal injuries, and provide specific preclinical measures of WM abnormalities for early diagnostics and accurate assessment of disease-modifying therapies targeting neuro-protection in AD.

Danielle van Westen¹, Sebastian Palmqvist², Henrik Zetterberg³, Niklas Mattsson², Lennart Minthon², Katarina Nägga², Erik Stomrud², The Swedish BioFINDER study², Kaj Blennow³, and Oskar Hansson^2
1Diagnostic Radiology, Lund University, Lund, Sweden, ²Memory Clinic, Lund University, Lund, Sweden, ³The Sahlgrenska Academy at University of Gothenburg, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Gothenburg, Sweden

White matter lesions (WML) are abundant in the elderly and even more so in Alzheimer’s disease (AD). Previous studies indicate that WML affect the level of cerebrospinal fluid (CSF) Aβ42 and this in turn might affect the validity of CSF Aβ42 as biomarker of the pathological hallmark of AD, namely cerebral amyloid deposition. Therefore, we studied the influence of WML on the association between CSF Aβ42 and amyloid deposition measured with [18F]-flutemetamol positron emission tomography (PET).

Shuang Yang¹, Tianyi Qian², Yao Meng³, Fei Gao¹, Josef Pfeuffer⁴, Guangbin Wang¹, and Bin Zhao^1
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, People's Republic of, ²Siemens Healthcare, MR Collaborations NE Asia, Beijing, China, People's Republic of, ³Shandong provincial Hospital, Shandong University, Jinan, China, People's Republic of, ⁴Siemens Healthcare, Application Development, Erlangen, Germany

This study aims to present the feasibility of multi-TI (mTI)-ASL in distinguishing between AD and SIVD patients in cerebral perfusion. Nineteen SIVD subjects, twelve AD subjects, and ten controls were included in the study. There was no significant difference in CBF between SIVD and HCs, and between SIVD and AD patients. However, significant differences of BAT were detected among all three groups. The mTI-ASL could evaluate the cerebral perfusion of AD and SIVD patients. Compared with CBF, the BAT could better detect perfusion differences and demonstrated better efficiency.

Tianyi Qian¹, Peipeng Liang², and Kuncheng Li^2
1MR Collaborations NE Asia, Siemens Healthcare, Beijing, China, People's Republic of, ²Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China, People's Republic of

In recent years, the study of dynamic changes within brain functional networkshas become a trend topic in the fields of neuroscience and neuroradiology. In this study, we proposed a time-pointbased analysis method to search for dynamic pattern changes in normal controls, AD and two MCI stages.We aim to investigate whether the DMN deficit we observed in previous studiesis related to changes of activity frequency of micro-state network condition.The results show that the dynamic patterns obtained by the time point-based analysis could detect several DMN micro-states and the frequency of the appearance of these micro-states changes during the progress of cognitive impairment.

Gunther Helms^1,2, Arne Wrede³, Peter Dechent², and Walter Schulz-Schaeffer^3
1Medical Radiation Physics, Lund University, Lund, Sweden, ²Cognitive Neurology, Göttingen University Medical Center, Göttingen, Germany, ³Neuropathology, Göttingen University Medical Center, Göttingen, Germany

Structural 3D MRI and FLASH-based mapping of T₁ and magnetization transfer (MT) at 3T was performed in situ on 11 subjects with probable Creutzfeldt-Jacob disease prior to autopsy. The mean diffusivity in ventricles yielded temperatures between 6°C and 29°C.  T₁ contrast in the deep brain decreased with temperature and vanished under refrigerated conditions. T₁ of gray matter lowered towards the normal white matter’s T₁ which did not change. The MT saturation was generally independent of temperature, except in normal WM below 13°C. Above 13°C, MT maps yield a high contrast and can be used for quantitative assessment of structural changes.

Marjolein Bulk¹, Walid M. Abdelmoula¹, Linda M. van der Graaf¹, Mark A. van Buchem¹, Pieter Voorn², Jouke Dijkstra¹, and Louise van der Weerd^1,3
1Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, ³Human Genetics, Leiden University Medical Center, Leiden, Netherlands

Investigating the histological correlates of MRI contrasts in patients with Alzheimer’s disease (AD) will give more insight into the pathological correlates of T2* and SWI. Using 7T MRI and histology of post-mortem brain tissue we showed that the frontal cortex of AD patients has a different imaging phenotype compared to non-demented controls, which spatially correlates to changes in iron deposition and grey matter myelin organization Most importantly, within the AD group the early-onset AD patients are distinguishable on MRI from the late-onset AD patients, and these differences are mirrored in the underlying pathology of these AD subtypes.  

Weiwei Wang¹, Jing Jing¹, Bing Wu², Ailian Liu¹, Qingwei Song¹, and Yanwei Miao^1
1Radiology Department, the First Affiliated Hospital of Dalian Medical University, Dalian, China, People's Republic of, ²GE Healthcare MR Research China, BeiJing, China, People's Republic of

AD concomitant with hyperglycemia is commonly observed during clinical work, and it was known that AD and disorder of glucose metabolism are related.However, the factor of glucose level in AD patients have not yet been taken into consideration in the past studies, which might be of clinical significance in learning the AD progression. In this work, DKI is used to probe the likely effects of elevated glucose level in the white matter microstructure of AD patients.

Lisa A. van der Kleij¹, Esben T. Petersen², Hartwig R. Siebner², Jeroen Hendrikse¹, Kristian S. Frederiksen³, Nanna A. Sobol⁴, Steen G. Hasselbalch³, and Ellen Garde^2
1Department of Radiology, UMC Utrecht, Utrecht, Netherlands, ²Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark, ³Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ⁴Musculoskeletal Rehabilitation Research Unit and Institute of Sports Medicine, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

The purpose of this study was to determine the effect of moderate-to-high-intensity aerobic exercise on cerebral blood flow in patients with Alzheimer’s disease (AD). In the ADEX trial, patients with mild to moderate AD participated in aerobic exercise for 16 weeks. Pulsed Arterial Spin Labeling was performed at baseline and at 16 weeks. CBF in the anterior cingulate cortex was significantly lower at 16 weeks in the control group, but it remained unchanged in the intervention group. Our results suggest  that even brains  affected by mild to moderate Alzheimer’s disease may still benefit from regular exercise.

Junxiao Yu¹, Aikaterini Kotrotsou¹, Arnold M. Evia¹, Julie A. Schneider², Sue E. Leurgans², David A. Bennett², and Konstantinos Arfanakis^1
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Transactive response DNA-binding protein 43 (TDP43) pathology was the primary protein abnormality in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Recent findings showed that TDP43 pathology is common in old age and strongly associated with cognition, cognitive decline and increased risk of dementia beyond the contributions of other age-related neuropathologies. TDP43 pathology in aging is mainly found in the medial temporal lobes with the being one of the first regions to be affected. The purpose of this project was to study associations of TDP43 in aging with amygdalar volume for the first time in a large community cohort.

Santosh Kumar Yadav¹, Georgia Vasileiou², Anup Singh³, Elias R Melhem⁴, Ena Wang¹, Francesco M Marincola¹, Arijitt Borthakur⁵, and Mohammad Haris^1
1Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar, ²Department of Medical physics, University college of Landon, Landon, United Kingdom, ³Center for Biomedical Engineering, Indian institute of Technology, Delhi, India, ⁴Department of diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States, ⁵Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

We evaluated the gender based differences in cortical thickness and structural brain network connectivity in PD patients. Significantly reduced cortical thicknesses and disrupted structural networks connectivity appeared in PD males compared to PD females suggestive of more brain tissue changes in PD males than PD females. These male-specific cortical thickness changes and disrupted structural networks connectivity may contribute to or derive from physiological and genetically differences between males and females and may have significant implications in diagnosing and treating PD among the gender.

Frances-Catherine Quevenco¹, Jiri van Bergen¹, Xu Li², Anton F. Gietl¹, Valerie Treyer^1,3, Rafael Meyer¹, Sandra E. Leh¹, Alfred Buck³, Roger Nitsch¹, Peter C. M. van Zijl², Christoph Hock¹, and Paul G. Unschuld^1
1Psychiatric Research, University of Zurich, Zurich, Switzerland, ²F.M. Kirby center for Functional Brain Imaging, Kennedy Krieger Institute and Johns Hopkins School of Medicine, Baltimore, MD, United States, ³Division of Nuclear Medicine, University of Zurich, Zurich, Switzerland

To investigate early stages of preclinical Alzheimer’s, this study investigates the functional connectivity of 25 cognitively healthy elderly participants (“super agers”) in relation to cortical iron (using QSM) and cortical amyloid-beta load (18F-Flutemetamol PET).  Functional connectivity analysis with the posterior cingulate cortex (PCC) as a seed found significant regional and temporal overlaps in primary DMN regions for groups with high iron and high amyloid. Despite the network synchronicities, a contrast between high iron and high amyloid networks found significant FC differences between the PCC, precuneus, hippocampus and parahippocampus which are DMN connections known to be affected by Aß-burden.

Thomas Bonde Larsen¹, Akshay Pai¹, and Sune Darkner^1
1Computer Science, University of Copenhagen, Copenhagen, Denmark

Effective and accurate diagnosis of Alzheimer’s disease (AD) purely based on structural magnetic resonance imaging (MRI) is a very pertinent clinical problem. We present a simple but highly accurate registration-based method to discriminate between the three classes of healthy controls (HC), mild cognitively impaired (MCI) and AD. The method uses the norm of the tangent space of the deformation in a K-nearest neighbor KNN classifier. The result show that for 60 subjects, 20 in each class using n-fold cross-validation an overall accuracy of 81.6% with 75% for HC, 85% MCI and 85% for AD.

XIANGZHU ZENG¹, HUISHU YUAN¹, YING LIU¹, and ZHENG WANG^1
1RADIOLOGY, PEKING UNIVERSITY THIRD HOSPITAL, BEIJING, China, People's Republic of

Mild cognitive impairment (MCI) is often considered as an intermediate stage between normal aging and dementia, as reflected by a higher rate of conversion to clinical Alzheimer’s disease (AD) than in the normal elderly population. The hippocampal formation is a complex brain region with a primary role in memory function and vulnerable to neurodegenerative diseases. The aim of this research is to investigate the atrophy feature of hippocampal subfield and follow up the changes of hippocampal subfield in about two years by using automatic segmentation tool in patients with MCI.Our results suggest that compared to ICV, hippocampal subfield could be a more sensitive to detect cerebral changes of MCI. CA1, CA3 and left entorhinal cortex may be main subfields involved during MCI stage. Volumes of hippocampal subfield decreased in MCI patients and were positive correlation with clinical scores. There were also decreases in volumes of hippocampal subfield in MCI patients with the progress of the disease.

Leonardo A Rivera-Rivera¹, Tilman Schubert², Kevin M Johnson¹, Sterling C Johnson³, Patrick Turski², and Oliver Wieben^1,2
1Medical Physics, University of Wisconsin Madison, Madison, WI, United States, ²Radiology, University of Wisconsin Madison, Madison, WI, United States, ³Medicine, University of Wisconsin Madison, 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 assess cerebral venous flow, particularly mean blood flow and pulsatility index in patients with AD, and in healthy age matched controls. We found a statistically significant increase in pulsatility index and decrease in mean flow for the AD in most venous segments. 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.

Rexford Newbould¹, Brandon Whitcher², Christopher Long³, Shaila Shabbir⁴, Paul Matthews⁵, Andrew Lockhart⁴, Craig Ritchie⁵, and Eugenii Ilan Rabiner^1
1Imanova, London, United Kingdom, ²Klarismo, London, United Kingdom, ³MIT Sloan School of Management, Cambridge, MA, United States, ⁴GSK, Brentford, United Kingdom, ⁵Imperial College London, London, United Kingdom

DCE 3T MRI data acquired from 6 subjects with previous diagnoses of AD, 2 subjects with vascular dementia, and 7 healthy controls group-matched for age and gender.  Radiofrequency transmit (B1) field corrected Gd concentration values were calculated via dual-temporal resolution dynamic T1 mapping during and over 45 minutes post rapid Gd infusion.  The extended Tofts model was used to determine the volume and rate transfer constants of BBB permeability in 11 regions of interest.  No differences were detected between groups, implying BBB leakage in AD is slower than detectable in this experiment, or that BBB permeability in AD is moderated by an active transport mechanism.

Jakob Meineke¹, Fabian Wenzel¹, Iain D. Wilkinson², and Ulrich Katscher^1
1Philips Research Europe, Hamburg, Germany, ²University of Sheffield, Sheffield, United Kingdom

Quantitative Susceptibility Mapping (QSM) is used to study the deep gray-matter nuclei of patients with Alzheimer’s Disease (AD) and healthy control subjects. QSM is performed using “Joint background-field removal and segmentation-Enhanced Dipole Inversion” (JEDI), which leverages the information from automated model-based segmentation and allows the compact single-step formulation of the ill-posed inversion problem of QSM. The tissue magnetic susceptibility shows a trend for increase in the amygdala and the putamen of AD patients as compared to healthy control subjects, in agreement with previous studies.

Nicola Bertolino¹, Michael G Dwyer¹, Paul Polak¹, Samuel Daniel Robinson², Robert Zivadinov^1,3, and Ferdinand Schweser^1,3
1Buffalo Neuroimaging Analysis Center, Department of Neurology,Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, ²High Field Magnetic Resonance Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ³MRI Molecular and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States

FLAIR* is a fusion of T2-FLAIR and 3D-T2*w images and it is used to assess the central-vein-sign, a recent promising research direction in MRI-based study of Multiple Sclerosis. However in this experiment we show that researchers should be aware that slight patient movement during acquisition can produce blurring effect in 3D-T2*w images. This subtle artifact can mask small vessels even in case which the overall quality of the image is not substantially degraded.

Mark J Lowe¹, Katherine Koenig¹, Erik Beall¹, Jian Lin¹, Ken Sakaie¹, Lael Stone², and Micheal D. Phillips^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Neurologic Institute, Cleveland Clinic, Cleveland, OH, United States

Based on the observation that anatomic and functional connectivity measures in multiple sclerosis (MS) are correlated, but not highly correlated, we propose to combine these metrics into an imaging based measure of disease progression. We show that this metric is sensitive to disease progression in a cohort of MS patients over a time period of one year.

Christoph Birkl¹, Daniele Carassiti², Christian Langkammer¹, Christian Enzinger¹, Franz Fazekas¹, Klaus Schmierer^2,3, and Stefan Ropele^1
1Department of Neurology, Medical University of Graz, Graz, Austria, ²Blizard Institute (Neuroscience), Queen Mary University of London, London, United Kingdom, ³Barts Health NHS Trust, Emergency Care and Acute Medicine Clinical Academic Group (Neuroscience), London, United Kingdom

Evidence for a possible role of iron in the pathogenesis and progression of multiple sclerosis (MS) has raised interest in iron mapping techniques. However, current approaches are not reliable in white matter because of the diamagnetic properties of myelin. We recently proposed a new method for iron mapping which is based on the temperature dependency of the paramagnetic susceptibility. Here, the temperature coefficient of R₂* (TcR₂*) as a measure of iron content was assessed in three post-mortem MS brain samples. Validation of TcR₂* mapping was done with immunohistochemistry using cell counting on ferritin light-chain stains.

Anna Combes¹, Lucy Matthews², Gareth J Barker¹, Steven CR Williams¹, Katrina McMullen³, Janet Lam⁴, Anthony Traboulsee³, David KB Li^3,4, Jacqueline Palace², and Shannon Kolind^3
1Neuroimaging, King's College London, London, United Kingdom, ²Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ³Medicine, University of British Columbia, Vancouver, BC, Canada, ⁴Radiology/UBC MS/MRI Research Group, University of British Columbia, Vancouver, BC, Canada

Neuromyelitis optica (NMO) severely affects the optic nerves and spinal cord and shares features with multiple sclerosis (MS). Ongoing diffuse neurodegeneration, however, is thought to be absent in NMO between relapses. We collected cervical cord mcDESPOT at baseline and one-year follow-up in patients and matched controls. While there were no significant changes in controls and MS patients, the NMO group showed a loss of cord volume, decrease in T₁ and increase in myelin water fraction. We hypothesize that continuing atrophy in lesioned areas reduces the amount of damaged tissue relative to healthy tissue, and is responsible for the observed changes.

Irene Vavasour¹, Sandra Meyers², Praveena Manogaran³, Shuhan Xiao³, Anika Wurl³, Katrina McMullan³, David Li¹, Anthony Traboulsee³, and Shannon Kolind^3
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ³Medicine, University of British Columbia, Vancouver, BC, Canada

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are both autoimmune diseases of the central nervous system. Normal appearing white matter is known to be affected by diffuse tissue damage in MS whereas damage in NMO is thought to be restricted to acute lesions. Surprisingly, in this study, water content within whole white matter and white matter tracts of subjects with neuromyelitis optica (NMO) was found to be higher than in healthy matched controls and similar to MS. Both NMO and MS lesions had a higher water content compared to normal appearing white matter.

Ottavia Dipasquale^1,2, Jamie Campbell³, Camila Callegari Piccinin⁴, Dawn Langdon⁵, Waqar Rashid⁶, and Mara Cercignani^3
1IRCCS, Don Gnocchi Foundation, Milan, Italy, ²Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy, ³Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom, ⁴Neuroimaging Laboratory, University of Campinas, Cidade Universitária, Campinas, Brazil, ⁵Psychology Department, Royal Holloway, University of London, Egham, United Kingdom, ⁶Department of Neurology, Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom

We investigated the resting-state functional connectivity (FC) changes induced after 6 weeks of computerised, home-based cognitive rehabilitation in patients with multiple sclerosis (MS) in a randomized controlled trial. The intervention and control groups were evaluated at baseline (T1), after a 6-week intervention period (T2) and a 12-week follow-up period (T3). Out of the 94 regions investigated, many memory-, attention- and motor-related areas strengthened their FC at T2 and T3 in the intervention group. This study supports the hypothesis that this cognitive rehabilitation is a feasible and effective approach in patients with MS and confirms that rfMRI is a useful tool for mapping plastic changes.

Timothy Shepherd^1,2, Ivan Kirov^1,2, James S Babb^1,2, Mary T Bruno², Robert E Charlson³, Jacqueline Smith², KAI Tobias Block^1,2, Daniel K Sodickson^1,2, and Noam Ben-Eliezer^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²The Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, United States, ³Department 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 associated with rapid multi-SE sequences. This inaccuracy is, moreover, not constant and depends on both the pulse sequence scheme and parameter-set employed, resulting in different vendors or scanners yielding different results! We used a recently developed novel T₂ mapping technique, the EMC algorithm, to quantify T₂ changes in different brain regions of MS patients. Our results demonstrate that the robustness of the EMC approach allows the detection of subtle, but statistically significant T₂ differences in normal appearing brain regions for MS patients.

Bernhard Strasser¹, Gilbert Hangel¹, Michal Považan¹, Stephan Gruber¹, Marek Chmelík¹, Assunta Dal-Bianco², Fritz Leutmezer², Siegfried Trattnig^1,3, and Wolfgang Bogner^1
1MRCE, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Neurology, Medical University of Vienna, Vienna, Austria,³Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

In this study fourteen MS patients were measured with an FID-based MRSI sequence at 7T with resolutions of 64x64 and 100x100. Metabolic maps of total NAA, total Choline, total Creatine, and myo-Inositol were compared to FLAIR images. All patients had lesions with decreased tNAA, and eight had increased myo-Inositol levels. However, not all lesions showed decreased tNAA values. Two patients showed decreased tNAA levels with no visible lesion on the FLAIR image. In average, a decrease of 26% in tNAA and an increase of 42% in myo-Inositol were observed in comparison to normal appearing white matter.

Adnan A.S. Alahmadi^1,2, Matteo Pardini^1,3, Rebecca S. Samson¹, Egidio D'Angelo^4,5, Karl J. Friston⁶, Ahmed T. Toosy^1,7, and Claudia Angela Michela Gandini Wheeler-Kingshott^1,5
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, ²Department of Diagnostic Radiology, Faculty of Applied Medical Science, KAU, Jeddah, Saudi Arabia, ³Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy, ⁴Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy, ⁵Brain Connectivity Center, C.Mondino National Neurological Institute, Pavia, Italy, Pavia, Italy, ⁶Wellcome Centre for Imaging Neuroscience, UCL, Institute of Neurology, London, United Kingdom, ⁷NMR Research Unit, Department of Brain Repair and Rehabilitation, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom

This study investigates how multiple sclerosis (MS) selectively affects regional BOLD response to variable grip forces (GF). It is known that the anterior and posterior BA4 areas are anatomically and functionally distinguishable – and that in healthy subjects there are linear and non-linear BOLD response components.  After modelling BOLD responses with a polynomial expansion of the applied GF during task, we showed that in BA4a MS subjects respond like healthy subjects. BOLD response in BA4p, instead, was altered in MS, with those with greatest disability showing the greatest deviations from the non-linear profile of the healthy response.

Paola Valsasina¹, Maria Assunta Rocca¹, Laura Vacchi¹, Alessandro Meani¹, Mariaemma Rodegher², Vittorio Martinelli², Giancarlo Comi², Andrea Falini³, and Massimo Filippi^1
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ³Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

In this study, we investigated behavioral and functional MRI (fMRI) correlates of a N-back task in 72 patients with multiple sclerosis (MS). We found a load-dependent alteration of executive network recruitment, varying according to the disease phenotype. Increased recruitment of frontal regions was associated to the early phase of MS. Conversely, the modulation of regions belonging to the default mode network was more evident in patients with long-lasting disease and was related to the global cognitive profile, suggesting an increased need of cognitive resources to cope with task-demand.

Ivan Kirov^1,2, Shu Liu^1,2, Assaf Tal³, William E. Wu^1,2, Matthew S. Davitz^1,2, James S. Babb^1,2, Henry Rusinek^1,2, Joseph Herbert⁴, and Oded Gonen^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ⁴Neurology, New York University Langone Medical Center, New York, NY, United States

Using MR imaging and proton spectroscopy, we follow the evolution of transient and persistent multiple sclerosis lesions from pre-lesional state to long-term (over 2 years post-formation) status. The main finding was that the sharp drop in N-acetyl-aspartate associated with the formation of an acute lesion was reversible in resolving, but not in persisting black holes, substantiating the idea that transient new lesions revert to pre-lesional axonal state. The additional findings were a decrease in creatine after the appearance of a persisting lesion and the lack of metabolic differences between pre-lesional tissue giving rise to resolving versus persisting lesions.

Richard J Dury¹, Molly G Bright¹, Yasser Falah², Penny A Gowland¹, Nikos Evangelou², and Susan T Francis^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ²Nottingham University Hospital, University of Nottingham, Nottingham, United Kingdom

Grey matter cortical lesions have been associated with physical disability, cognitive impairment and fatigue in Multiple Sclerosis. Only one previous study has assessed cerebral blood flow (CBF) and cerebral blood volume (CBV) within cortical lesions. Here we use high spatial resolution 7T FAIR TrueFISP ASL to assess the perfusion in grey matter cortical lesions and compare this to surrounding normal appearing grey matter. Cortical lesions showed a significant 32% reduction in perfusion signal compared to normal appearing grey matter. This ASL method can be used to evaluate longitudinal perfusion changes in new and chronic cortical lesions.

Benedetta Bodini¹, Francesca Branzoli^1,2, Emilie Poirion¹, Daniel Garcia-Lorenzo^1,2, Elisabeth Maillart¹, Julie Socha¹, Geraldine Bera¹, Itamar Ronen³, Stephane Lehericy^1,2, and Bruno Stankoff^1
1Brain and Spine Institute, INSERM U1127, Sorbonne Universités, UPMC, CHU Pitié-Salpêtrière, Paris, France, ²Brain and Spine Institute, Center for Neuroimaging Research (CENIR), CHU Pitié-Salpêtrière, Paris, France, ³C.J. Gorter Center for High Field MRI, Radiology, Leiden University Medical Center, Leiden, Netherlands

Diffusion-weighted spectroscopy (DWS), allowing to measure in-vivo the diffusion properties of endogenous intracellular metabolites such as total N-acetyl-aspartate (tNAA) and total creatine (tCr), offers the opportunity to explore the early phase of neuronal structural damage and energetic mismatch in multiple sclerosis (MS). We compared the apparent diffusion coefficient (ADC) of tNAA and tCr in 25 patients with MS and 20 healthy volunteers, and found a reduced diffusivity of both metabolites in patients, both in the corona radiate and in the thalami. These results may reflect an ongoing neuro-axonal damage and a simultaneous energy dysregulation affecting neurons and/or glial cells in MS.

Amber Michelle Hill¹, Mohamed Tachrount², David L Thomas³, Kenneth J Smith⁴, Xavier Golay⁵, and Olga Ciccarelli^1
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, United Kingdom, ²Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, United Kingdom, ³Leonard Wolfson Experimental Neurology Centre, UCL Institute of Neurology, University College London, London, United Kingdom, ⁴Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom, ⁵Department of Brain Repair and Rehabilitation, Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom

EAE, an animal model of MS, can be investigated with MR to address the clinical need to understand mechanisms of the MS disease course. Longitudinal MR studies with EAE are currently under-explored. This study investigated longitudinal changes in metabolite concentrations and lesion development, in relation to neurological deficits in EAE, using 9.4T MRI and ¹H-MRS. Five time-points of EAE disease progression were assessed. The results suggest that before visible signs of neurological deficits, higher [NAA] predicts the severity of late-stage neurological deficits in EAE. Considering NAA is predominantly associated with neuronal mitochondria, this may reflect relevant pathological processes in MS.

Ivan Kirov^1,2, Shu Liu^1,2, Assaf Tal³, William E. Wu^1,2, Matthew S. Davitz^1,2, James S. Babb^1,2, Henry Rusinek^1,2, Joseph Herbert⁴, and Oded Gonen^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ⁴Neurology, New York University Langone Medical Center, New York, NY, United States

We describe the evolution of chronic multiple sclerosis lesions from a quantitative MR imaging and spectroscopy perspective. Metabolite concentrations were obtained along with measures of lesion T1-hypointensity and size. Moderately hypointense lesions were more metabolically active than severely hypointense lesions, driving an increase in the glial marker myo-inositol. Correlational analyses revealed that lesion size is a better predictor of axonal health than T1-hypointensity, with lesions larger than 1.5 cm³ exhibiting terminal axonal injury. A positive correlation between changes in choline and in lesion size in moderately hypointense lesions implied that changes in lesion size are mediated by chronic inflammation.

Jameen ARM¹, Scott Quadrelli², Karen Ribbons³, Jeanette Lechner-Scott³, and Saadallah Ramadan^4
1Imaging, HMRI, Newcastle, Australia, ²Imaging, TRI Brisbane, Brisbane, Australia, ³Neurology, John Hunter Hospital, Newcastle, Australia, ⁴Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia

¹H Magnetic Resonance Spectroscopic techniques (1H-MRS) have been utilised to assess inflammatory nature of both acute and chronic lesions as well as normal appearing brain tissue to understand the neuro degenerative irreversible component of multiple sclerosis (MS) from early stages^1-3. However, due to high spectral overlap in one-dimensional (1D) ¹H-MRS, it has been challenging to establish a standard specific spectral pattern in plaques or normal appearing brain tissues. L-COSY might provide the needed spectral dispersion

Michael Ingrisch¹, Steven Sourbron², Moritz Schneider¹, Sina Herberich³, Tania Kümpfel⁴, Reinhard Hohlfeld⁴, Maximilian Reiser³, and Birgit Ertl-Wagner^3
1Josef-Lissner-Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Ludwig-Maximilians-University Munich, Munich, Germany, ²Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom, ³Institute for Clinical Radiology, Ludwig-Maximilians-University Munich, Munich, Germany, ⁴Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich, Munich, Germany

Several studies have reported diffuse hypoperfusion in normal-appearing white matter(NAWM) in patients with relapsing-remitting multiple sclerosis(RR-MS). Here, we investigate this issue using dynamic contrast-enhanced (DCE)MRI. The statistical power of a DCE-MRI acquisition to reveal hypoperfusion was estimated for n=16 patients at 96% using a Monte-Carlo simulation. 24 patients with RR-MS and 16 healthy controls underwent a DCE-MRI examination and cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability-surface area product (PS) were quantified in NAWM, revealing no significant differences between groups. This indicates that, in our patient cohort, NAWM  hypoperfusion is much less pronounced than in previous DSC studies.

Elisabetta Pagani¹, Maria Assunta Rocca^1,2, Ermelinda De Meo¹, Bruno Colombo², Mariaemma Rodegher², Giancarlo Comi², Andrea Falini³, and Massimo Filippi^1,2
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ³Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Aim of the study was to quantify structural connectivity integrity in multiple sclerosis (MS) patients with different clinical phenotypes, to simulate a disconnection due to T2 visible lesions and to test its effect on network based measures. Diffusion tensor MRI was obtained from 239 MS patients and 131 healthy controls; connectivity matrices were produced and then artificially disconnected based on T2 visible lesion distribution. Global and nodal network metrics were calculated for both cases. Crucial nodes of the network were found to be different in strength between MS phenotypes. Disconnection simulation highlighted the role of T2 lesions in determining structural connectivity abnormalities.

Anagha Deshmane¹, Kunio Nakamura², Deepti K Guruprakash², Yun Jiang ¹, Dan Ma³, Jar-Chi Lee ⁴, Elizabeth Fisher ⁵, Richard A. Rudick ⁵, Jeffrey A. Cohen⁶, Mark J. Lowe⁶, Daniel Ontaneda⁶, Mark A. Griswold^1,3, and Vikas Gulani^1,7
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States, ³Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁴Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States, ⁵Biogen, Boston, MA, United States, ⁶Mellen Center for Multiple Sclerosis Research and Treatment, Cleveland Clinic, Cleveland, OH, United States, ⁷Radiology, University Hospitals, Cleveland, OH, United States

Magnetic Resonance Fingerprinting (MRF) is used to simultaneously map T₁, T₂, and spin density in the normal appearing white matter and normal appearing grey matter of multiple sclerosis patients and healthy controls.  Relaxation parameters measured by MRF are found to be significantly different between MS subjects and healthy controls, to distinguish between relapsing remitting MS and secondary progressive MS in certain brain structures, and to correlate with clinical measures of function and disability.

Sneha Pandya¹, Yan Zhang¹, Thanh Nguyen¹, Yi Wang¹, Susan A Gauthier², and Sneha Pandya^1
1Department of Radiology, Weill Cornell Medicine, New York, NY, United States, ²Department of Neurology, Weill Cornell Medicine, New York, NY, United States

MRI-derived measures of lesion accrual and tissue loss have acquired a central role in the understanding of MS disease evolution, pathogenesis of symptoms, and prediction of clinical outcome. Conventional MRI imaging is highly sensitive for detection of MS lesions, which are characteristically hyperintense on a T2 weighted images, however this technique lacks pathological specificity. QSM can help identify myelin and iron content changes during an MS lesion’s lifetime.

Paola Valsasina¹, Maria Assunta Rocca¹, Emanuele Pravatà^1,2, Gianna Riccitelli¹, Giancarlo Comi³, Andrea Falini⁴, and Massimo Filippi^1
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Department of Neuroradiology, Neurocenter of Southern Switzerland, Lugano, Switzerland, ³Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ⁴Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

In this study, we investigated cortical thickness abnormalities associated with cognitive impairment and depression in 126 patients with multiple sclerosis (MS). Compared with controls, MS patients exhibited a widespread bilateral cortical thinning involving all brain lobes. While cognitive impairment was associated with atrophy of regions located in the fronto-parietal lobes (including the middle and superior frontal gyrus, the inferior parietal lobule and the precuneus), depression was linked to atrophy of the orbitofrontal cortex. This study shows that cortical thickness analysis was able to detect specific effects of clinical symptoms on cortical atrophy in MS.

Eric Schrauben¹, Sarah Kohn², Samuel Frost², Oliver Wieben^2,3, and Aaron Field^2
1Centre for Advanced MRI, University of Auckland, Auckland, New Zealand, ²Radiology, University of Wisconsin - Madison, Madison, WI, United States, ³Medical Physics, University of Wisconsin - Madison, Madison, WI, United States

Contrast-enhanced MR venography scoring in internal jugular veins is performed and compared with 4D flow MRI and ultrasound assessment in patients with multiple sclerosis, patients with other neurological disorders and healthy controls. Narrowing  assessment is shown to be more variable in flow MRI and ultrasound.

Yaou Liu¹, Yunyun Duan², Huiqing Dong², Tianyi Qian², Frederik Barkhof³, Jinhui Wang⁴, and Kuncheng Li^2
1Xuanwu Hospital,Capital Medical University, Beijing, China, People's Republic of, ²Beijing, China, People's Republic of, ³Amsterdam, Netherlands, ⁴Hanzhou, China, People's Republic of

Combining double-inversion-recovery (DIR), high-resolution structural MRI, diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI), this study systematically investigated structural and functional alterations in grey-matter (GM) structures in thirty-five neuromyelitis optica (NMO) patients compared with healthy controls. We demonstrated that NMO exhibits both structural and functional alterations of GM in the cerebrum and cerebellum. Multimodal MRI techniques complementary worked to capture NMO-related GM abnormalities. GM alterations, especially diffusion abnormalities, correlated with cognitive impairment in NMO. These findings have important implications for understanding the roles of GM damage and also for highlighting multimodal MRI techniques as objective biomarkers in NMO.

Ferdinand Schweser^1,2, Nicola Bertolino¹, Michael G Dwyer¹, Jesper Hagemeier¹, Paul Polak¹, Niels P Bergsland^1,3, Andreas Deistung⁴, Bianca Weinstock-Guttman⁵, Jürgen R Reichenbach^4,6, and Robert Zivadinov^1,2
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, ²MRI Molecular and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, ³MR Research Laboratory, IRCCS Don Gnocchi Foundation ONLUS, Milan, Italy, ⁴Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany,⁵Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, ⁶Michael Stifel Center for Data-driven and Simulation Science Jena, Friedrich Schiller University Jena, Jena, Germany

Quantitative susceptibility mapping (QSM) is the most sensitive technique currently available to study brain iron in vivo. The technique opens the door to a longitudinal assessment of brain iron, bearing the potential to understand and disentangle factors resulting in the large scatter of reported iron concentrations in later decades of life. 

In the present work, we investigated longitudinal changes of brain magnetic susceptibility in a cohort of 40 healthy controls (HCs) and 160 multiple sclerosis (MS) patients over a period of 2 years.

Zsofia I. Kovacs¹, Tsang-Wei Tu¹, Georgios Z. Papadakis^1,2, William C. Reid², Dima A. Hammoud², and Joseph A. Frank^1,3
1Frank Laboratory, Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States, ²Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States, ³National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, United States

One potential issue for using MR-guided pulsed Focused Ultrasound (pFUS) to open the blood brain barrier (BBB) is the lack of data on the long term effects. Safety determination in the brain have been limited to the MR characterization after repeated BBB opening that can be achieved without hemorrhage, edema and behavioral changes in non-human primates (Arvanitis, et al. 2015; Downs, et al. 2015). We use multimodal imaging technics to characterize long term effects of pFUS + MB in the rat brain.

Sameer Shah¹, Qun He¹, Micheal Carl², Justin Brown¹, Mark Mahan³, Graeme M. Bydder¹, and Nikolaus M. Szeverenyi^1
1University of California, San Diego, San Diego, CA, United States, ²Global MR Applications & Workflow, General Electric, San Diego, CA, United States, ³Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, United States

The objective of this paper is to describe the use of several new approaches for magnetic resonance (MR) imaging of peripheral nerves. MR examinations were performed on fresh human median, tibial and sciatic nerve samples, as well as cadaveric forearms at 3T and/or 11.7T as well as one fresh human median nerve sample.  Application of MR techniques used elsewhere in the body, and the use of MR microscopy show a variety of new imaging findings in peripheral nerve. This approach is likely to improve understanding of the MR appearances of peripheral nerve and lead to improved experimental and clinical studies.

Eric Aliotta^1,2, Holden H Wu^1,2, and Daniel B Ennis^1,2
1Radiological Sciences, UCLA, Los Angeles, CA, United States, ²Biomedical Physics IDP, UCLA, Los Angeles, CA, United States

Spin Echo EPI Diffusion Weighted MRI (SE-EPI DWI) is widely used for neuro applications because of its speed. Conventional SE-EPI DWI approaches, however, often require long echo times (TE) which degrade SNR. Because SNR is inherently limited in high b-value DWI, TE must be kept as short as possible to ensure high-quality DWI. A Convex Optimized Diffusion Encoding (CODE) framework was developed to design waveforms which eliminate sequence dead times and minimize TE. CODE gradients were designed and implemented on a 3.0T scanner and demonstrated improved SNR in neuro DWI for healthy volunteers.

Mona ElSheikh¹, AbdelAziz ElNekiedy¹, Ihab Samy Reda¹, and Tarek Rashad Saleh^1
1Radiology, Alexandria University Hospitals, Alexandria, Egypt

Elderly patients often present with ventriculomegaly, not only with normal aging, but also due to a multitude of neurological disorders. The aim of this work was to study the role of MR CSF flow studies in assessment of elderly patients with ventriculomegaly. We identified variable underlying causes of ventriculomegaly in 20 elderly subjects including communicating hydrocephalus, obstructive hydrocephalus, and age-related cerebral atrophy.

Hui-Feng Ho^1,2, Hung-Chieh Chen², Hsin Tung³, Yi-Hsin Tsai⁴, Yi-Ying Wu², Jyh-Wen Chai^2,4, Clayton Chi-Chang Chen², Shin-Lei Peng¹, Wu-Chung Shen¹, and Tzu-Ching Shih^1
1Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, ²Radiology, Taichung Veterans General Hospital, Taichung, Taiwan, ³Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan, ⁴College of Medicine, China Medical University, Taichung, Taiwan

Cerebrospinal fluid (CSF) is the fluid circulating through the subarachnoid space and providing a neuroprotective function as a hydraulic cushion for the brain and the spinal cord. CSF not only plays a vital role for normal brain function, but also servers numerous important functions in the central nervous system. However, CSF leaks are a key cause of new-onset headaches. Despite numerous reports characterizing CSF and its circulation in subarachnoid space, our understanding of CSF leakage remains limited. In this study, we calculate the CSF volumes in the brain and the spine of SIH patients using T2-weighted MRI images.

Rafal Janik¹, Lynsie A.M. Thomason², and Greg J. Stanisz^1,2,3
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ³Department of Nerurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, Poland

We previously have demonstrated that administration of Lactobacillus rhamnosus (JB-1) to healthy male BALB/c mice, promotes consistent changes in GABA-A and -B receptor subtypes in specific brain regions, accompanied by reductions in anxiety and depression-related behaviours.  In the present study, using magnetic resonance spectroscopy (MRS), we quantitatively assessed two clinically validated biomarkers of brain activity and function, glutamate + glutamine (Glx) and total N-acetyl aspartate + N-acetylaspartylglutamic acid (tNAA), as well as GABA, the chief brain inhibitory neurotransmitter. 

Andrew Melbourne¹, Eliza Orasanu¹, Zach Eaton-Rosen¹, Manuel J Cardoso¹, Joanne Beckmann², Lorna Smith³, David Atkinson³, Neil Marlow², and Sebastien Ourselin^1
1Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ²Institute for Women's Health, University College London, London, United Kingdom, ³University College Hospital, London, United Kingdom

This abstract presents an analysis of brain tissue volume in a cohort of 69 extremely preterm born young adults and 50 term-born controls at 19 years of age.

Aditya N Bade¹, Jingdong Dong², Howard E Gendelman¹, Michael D Boska^1,3, and Yutong Liu^1,3
1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Omaha, NE, United States, ²Second Affiliated Hospital, Dalian Medical University, Dalian, China, People's Republic of, ³Department of Radiology, University of Nebraska Medical Center, Omaha, Omaha, NE, United States

Rats with acute and chronic nicotine exposure were studied using manganese-enhanced MRI (MEMRI). Neuronal activity was found on nucleus accumbens and hippocampus in rats with acute nicotine exposure, and on nucleus accumbens and hippocampus, prefrontal and insular cortex. The neuronal activity was confirmed by immunohistology. The above-mentioned brain regions are believed to play roles in drug addiction. We demonstrate that MEMRI can be used to assess neuroadaptations from nicotine addiction.

Shir Hofstetter¹ and Yaniv Assaf^2
1sagol school of neuroscience, tel aviv university, tel aviv, Israel, ²tel aviv university, tel aviv, Israel

The hippocampus plays an important role in spatial and non-spatial episodic memory. Using DTI, a micro-structural probe sensitive to rapid neuroplasticity, and the Morris water maze, we investigated spatial preference for place and time in the hippocampus as revealed by changes in diffusion indices induced by learning of a specific location in the maze and the overall training experience. We were able to find a system-level mapping of space and time in the rat hippocampus.

Eliza Orasanu¹, Andrew Melbourne¹, Zach Eaton-Rosen¹, David Atkinson², Alexandra Saborowska³, Joanne Beckmann⁴, Neil Marlow⁴, and Sebastien Ourselin^1
1Translational Imaging Group, Centre for Medical Image Computing, University College London, London, United Kingdom, ²University College London, London, United Kingdom, ³University College Hospital, London, United Kingdom, ⁴Institute for Women's Health, University College London, London, United Kingdom

Preterm born individuals may be subject to abnormal gyrification, associated with behavioural-cognitive deficit. In this work we perform a cortical folding analysis of the white-grey matter boundary in extremely preterm born young adults when compared to their term born peers, through a groupwise analysis using joint spectral matching. The results show that there are significant differences in folding in the temporal lobe, results which could be connected with poor executive function and language deficits in the extremely preterm cohort.

Zhang Xiaoqi¹, Ni Hongyan¹, and Qian Tianyi ^2
1Tianjin First Central Hospital, Tianjin, China, People's Republic of, ²MR Collaboration NE Asia, Siemens Healthcare, Beijing, China, People's Republic of

To quantify the iron loading in the whole body among transfusion-dependent patients, 32 transfusion-dependent patients and 32 healthy volunteers were recruited to participate in this study. The quantitative susceptibility mapping was processed to get the susceptibility of the ROIs in the brain, and T2*values of their livers, pancreas and myocardium. Significantly higher iron levels in the putamen were found in transfusion-dependent patients (right/left=0.147±0.066/0.149±0.811ppm) compared with healthy controls(right/left=0.064±0.037/0.060±0.326ppm) (P=0.021/0.011). A ROC curve was performed, and the results suggested that liver T2* and pancreas T2* values can be great predictors to diagnose the iron overload in the brain ( AUC=0.877, 0.974, P<0.01).

Bogdan G Mitrea¹, Ralf B Loeffler¹, Ruitian Song¹, and Claudia M Hillenbrand^1
1Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN, United States

For longitudinal investigations reproducibility and accuracy of ASL measurements are of essence. The purpose of this study is to investigate how magnet design and labeling position within the magnet impact CBF quantification. Our results indicate that CBF values are not always reproducible in our ultra-short wide bore scanner. Great variability may be introduced by the actual position of the labeling slice with respect to the magnet isocenter. The exact cause of this difference requires further investigation. However, positioning the labeling slice in isocenter provided a simple solution to overcome this issue and to measure reproducible CBF values.

Zhuozhi Dai^1,2, Phillip Zhe Sun³, Gang Xiao⁴, Gen Yan², Yanlong Jia², Zhiwei Shen⁵, Alan H. Wilman¹, and Renhua Wu^2,5
1Biomedical engineering, University of Alberta, Edmonton, AB, Canada, ²Medical Imaging, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China, People's Republic of, ³Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA, United States, ⁴Math and Information Technology, Hanshan Normal University, Chaozhou, China, People's Republic of, ⁵Provincial key laboratory of medical molecular imaging, Shantou, China, People's Republic of

pH is a very important biochemical property that changes in many pathological states. Monitoring pH is of significance in early diagnosis and treatment therapy. However, there is lack of non-invasive methods to image pH in vivo effectively. Our study quantified the pH value using a chemical exchange saturation transfer (CEST) method in rat brain and established a strong correlation of pH between CEST and 31P-MRS in vivo, Pearson correlation factor is 0.819, P < 0.01. Because CEST imaging has superior spatial resolution to 31P-MRS, CEST may provide an alternative, straightforward, and effective way to obtain quantitative pH images in vivo.

Melissa M Ong¹, Alexander Schmidt¹, Daniel Hausmann¹, Stefan O Schoenberg¹, and Stefan Haneder^1
1Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim, Germany

Although ²³Na-MRI can offer additional information regarding tissue function and viability compared to ¹H-MRI several obstacles have impeded its clinical implementation, including hardware costs and technical challenges. One step towards a more widespread clinical use of ²³Na-MRI would be the use of double-tuned (¹H/²³Na) coils. This would require morphologic and functional images with diagnostic image quality. The purpose of this study was therefore to prospectively compare image quality of a double-tuned (¹H/²³Na) vs. a clinically used ¹H head coil in healthy subjects. Image data of both coils showed excellent image quality with no significant differences in SNR. 

Elodie A. Pérès^1,2, Fawzi Boumezbeur¹, Olivier Etienne², Antoine Grigis¹, François D. Boussin², and Denis Le Bihan^1
1UNIRS, NeuroSpin, I2BM, Life Sciences Division, Commissariat à l’Energie Atomique, Gif-sur-Yvette, France, ²Laboratoire de Radiopathologie, SCSR, iRCM, UMR 967, Life Sciences Division, Commissariat à l’Energie Atomique, Fontenay-aux-Roses, France

Patients frequently suffer from cognitive impairments following brain radiotherapy. Ionizing radiations are known to induce various brain alterations and impair neurogenesis. Following whole cerebral irradiation (3X5 Gy), we found significant changes in non-Gaussian water diffusion parameters (ADC₀ and kurtosis) and related S-index, a new diffusion biomarker sensitive to changes in tissue microstructure, in the subventricular zone, a site of adult neurogenesis and in the olfactory bulbs. MRS exhibited a longitudinal decrease in taurine specifically in the olfactory bulbs. These results suggest that diffusion MRI and MRS could be used to monitor changes induced by radiation injury.

Jiayu Zhang¹, Taous Meriem Laleg¹, Stephanie Bogaert², Rik Achten^2,3, and Hacene Serrai^2,3
1Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia, ²Department of Radiology, University Hospital of Gent, gent, Belgium, ³University of Gent, Gent, Belgium

A magnetic resonance imaging denoising method based upon the spectral analysis of the shrodinger operator is proposed.The method called semi-classical signal analysis SCSA, employs an adaptive filter to represent the MRI image as a set of useful vectors and others representing noise. The separation between signal and noise vectors is achieved using a soft and efficient threshold. Method validation is achieved on anatomical brain images acquired with low signal to noise ratio. The obtained results demonstrate that the SCSA is efficient in reducing noise while preserving image details necessary for accurate image diagnosis.

Sarah C Wayte¹, Victoria Sherwood¹, Ravjit Sagoo¹, Eddie Ng'andwe¹, Charles E Hutchinson^1,2, and Christopher HE Imray^1,2
1University Hospitals Coventry and Warwickshire, Coventry, United Kingdom, ²Warwick Medical School, Warwick University, Coventry, United Kingdom

The apparent changes in venous calibre on susceptibility weighted imaging (SWI) of six normal volunteers pre-hypoxia, during the first 12 minutes of hypoxia, and at 30 and 60 minutes were investigated. For all subjects there was a step increase in apparent venous calibre on SWI which occurred within the first few minutes of hypoxia, and this was maintained up to 60 minutes. The apparent increase in venous calibre occurred too rapidly after hypoxia induction to be entirely due to an increase in vessel volume. The vessels appear dilated because of the greater magnetic susceptibility of deoxyhaemoglobin than oxyhaemoglobin. 

Puneet Bagga¹, Kevin D'Aquilla¹, Mohammad Haris², Hari Hariharan¹, and Ravinder Reddy^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Research Branch, Sidra Medical and Research Center, Doha, Qatar

Nicotinamide adenice dinucleuotide (NAD⁺) is a ubiquitous molecule present in all cells and tissues of the body with an important role in the redox reactions and metabolism. Small changes in NAD levels may lead to oxidative stress and may be a cause for various disorders. Currently, NAD can be detected in vivo only by ³¹P NMR spectroscopy. Chemical Exchange Saturation Transfer (CEST) MRI is an imaging technique which exploits the properties of exchangeable protons on the molecule for imaging. In the present study, we have shown the in vitro CEST effect of solution containing NAD⁺. 

Lucette A Cysique¹, James R Soares², John Geng³, Maia Scarpetta^3,4, Bruce J Brew^2,5, Roland Henry⁶, and Caroline D Rae^7
1UNSW Australia, NeuRA, Sydney, Australia, ²UNSW Australia, Sydney, Australia, ³NeuRA, Sydney, Australia, ⁴Reed College, Portland, WA, United States, ⁵St. Vincent's Hospital, Sydney, Australia, ⁶UCSF, San Francisco, CA, United States, ⁷The University of New South Wales, Randwick, Australia

DTI was performed in 40 HIV- men and 82 HIV+ men with comparable demographics and life styles. The study was designed to recruit chronic HIV+ participants with successful viral control. DTI was 32 directions; FA values were quantified in each participant in 12 skeleton regions of interest, which have been associated with HIV-related brain injury. The study present first evidence for complex brain repair processes in treated and chronic HIV infection arguing for careful multilevel characterization of HIV+ samples in neuroHIV DTI studies. The association of neurocognitive function with FA suggests ongoing vulnerability despite successful treatment.

Chao Chai¹, Linlin Fan², Chao Zuo³, Mengjie Zhang³, Lei Liu³, Zhiqiang Chu⁴, Tianyi Qian⁵, E Mark Haacke⁶, Shuang Xia³, and Wen Shen^3
1Department of Radiology, Tianjin First Central Hospital, Tianjin Medical University First Central Clinical college, Tianjin, China, People's Republic of, ²Department of Prophylactic Inoculation, Tianjin First Central Hospital, Tianjin Medical University First Central Clinical College, Tianjin, China, People's Republic of, ³Department of Radiology, Tianjin First Central Hospital, Tianjin Medical University First Central Clinical College, Tianjin, China, People's Republic of, ⁴Department of Haemodialysis, Tianjin First Central Hospital, Tianjin Medical University First Central Clinical college, Tianjin, China, People's Republic of, ⁵MR Collaboration NE Asia, Siemens Healthcare, Beijing, China, People's Republic of, ⁶Department of Radiology, Wayne State University, Detroit, MI, United States

The aim of this study was to explore cerebral venous oxygen saturation changes in long-term hemodialysis (HD) patients using susceptibility mapping (SWIM). SWIM was reconstructed from phase data of SWI and used to measure the susceptibility of cerebral veins in HD patients and healthy controls respectively. The results suggested that SWIM was a feasible and reliable method to measure the venous oxygen saturation. It can show the decrease of CMRO₂ in HD patients and the susceptibility value of the left cerebral cortical vein is positively correlated with MMSE scores.

Christopher B Miller¹, Caroline D Rae², Michael Green², Brendon Yee^1,3, Christopher J Gordon^1,4, Nathaniel S Marshall¹, Simon D Kyle⁵, Colin A Espie⁵, Ronald R Grunstein¹, and Delwyn J Bartlett^1
1NeuroSleep and Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia, ²The University of New South Wales, Randwick, Australia, ³3 Department of Respiratory and Sleep Medicine, RPAH, Sydney, Australia, ⁴Sydney Nursing School, Sydney, Australia, ⁵Nuffield Department of Clinical Neurosciences and Sleep & Circadian Neuroscience Institute, The University of Oxford, Oxford, United Kingdom

We investigated 31 subjects with Insomnia Disorder grouped by hierarchical cluster analysis into long (N = 19) or short (N = 12) sleep duration insomnia and 16 healthy, good sleeping controls using an aymmetric PRESS MRS sequence at 3T in the left occipital cortex. A super metabolite variable constructed from creatine, Asp, Glu and Gln separated short sleeping insomnia from long sleeping  and controls,  positively correlated with total sleep duration and negatively with wake-time after sleep onset. Short sleep is associated with reduced creatine concentration.

Rachel D. Freed¹, Barbara J. Coffey¹, Xiangling Mao², Guoxin Kang², Nora Weiduschat², Dikoma C. Shungu², and Vilma Gabbay^1
1Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Weill Medical College of Cornell University, New York, NY, United States

γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, may play a role in the pathophysiology of Tourette’s disorder (TD). We used ¹H MRS to measure GABA in the anterior cingulate cortex (ACC) and striatum of adolescents with TD and healthy controls (HC). Adolescents with TD had lower GABA spectra in the ACC than HC, suggesting a role for dysregulated ACC neurotransmitter function. Within the TD group, ACC GABA was positively associated with tic severity, potentially related to attempts at regulating or suppressing tics. Findings provide evidence for dysfunction of the central GABAergic system in TD.

Birte Schmitz¹, Anita B. Tryc², Karin Weißenborn², Henning Pflugrad², Heinrich Lanfermann¹, and Xiao-Qi Ding^1
1Institute for Neuroradiology, Hannover Medical School, Hannover, Germany, ²Institute for Neurology, Hannover Medical School, Hannover, Germany

Patients treated with immunosuppressive calcineurin inhibitors (CNI) for at least 3 years after liver transplantation were studied by using non-localized whole brain 31P-MRS at 3T to evaluate possible chronic neurotoxic side effects of the CNI. Global concentrations of brain high-energy metabolites Adenosine-5'-triphosphate (ATP) and phosphocreatine (PCr) were estimated. The values of the patient with different doses of CNI were compared with those of age-matched healthy volunteers. In our preliminary results significant lower concentrations of ATP and PCr were found in patients treated both with standard and low doses of CNI, indicating possible neurotoxic side effects.

Pauline W Worters¹, Dirk Beque², Robert D Peters³, Dominic Graziani⁴, Michael Carl⁵, Graeme C McKinnon³, and Christopher J Hardy^4
1GE Healthcare, Menlo Park, CA, United States, ²GE Global Research, Munich, Germany, ³GE Healthcare, Waukesha, WI, United States, ⁴GE Global Research, Niskayuna, NY, United States, ⁵GE Healthcare, San Diego, CA, United States

A silent 3D multi-echo gradient-echo pulse sequence is developed for quantitative susceptibility mapping (QSM). The new, silent sequence is compared to the standard acquisition and gives comparable susceptibility values. The silent acquisition gives the benefit of patient comfort and workflow ease at some cost to SNR and acquisition time.

Abdullah Asiri^1,2, Charles Watson³, Shalini Nair⁴, Gary Cowin¹, Marc Ruitenberg⁵, and Nyoman Kurniawan^1
1Centre for Advanced Imaging, University of Queensland, Brisbane, Australia, ²Najran University, Najran, Saudi Arabia, ³Faculty of Health Sciences, Curtin University of Technology, Perth, Australia,⁴National University Hospital Systems, Kent Ridge, Singapore, ⁵School of Biomedical sciences, The University of Queensland, Brisbane, Australia

Imaging the spinal cord is normally performed at lower magnetic field with limited resolution. In this study, 13 ex-vivo cervical spinal cords have been scanned at 9.4T to provide high-resolution images. A variation of the position of the rostral brachial motorneurons among the cords was used to classify the samples into normal and pre-fixed types.  For each segment, the length and GM/WM total areas were measured. A high resolution MRI template of the normal type samples was created to assist registration and delineation of spinal cord structures and improve the accuracy of diagnostic radiology. 

Patrick W. Hales¹, Kshitij Mankad², Patricia O'Hare², Victoria Smith², Darren Hargrave², and Christopher Clark^1
1Developmental Imaging & Biophysics Section, University College London Institute of Child Health, London, United Kingdom, ²Great Ormond Street Children's Hospital, London, United Kingdom

Conventional MRI sequences have so far failed to provide imaging biomarkers that reliably differentiate asymptomatic optic pathway glioma (OPG) tumours from those which cause visual impairment. ADC maps are now acquired as standard in most institutions, and despite their typically limited resolution, may provide quantitative assessment of tumour invasion of the optic nerve. We measured ADC and optic nerve thickness using standard clinical imaging sequences in OPG patients, in conjunction with visual assessment. We found that the product of ADC and nerve thickness showed a significant correlation with visual acuity, and was significantly increased in patients who had gone blind.  

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

Combining the contrast of susceptibility weighted imaging (SWI) and fluid-attenuated inversion recovery (FLAIR) allows simultaneous visualization of multiple sclerosis lesions and the penetrating veins and iron deposition. However, the need for image registration, to account for patient motion between the scans, adds to the complexity of the post-processing pipeline, and introduces undesirable blurring of the image. We have developed an interleaved sequence for simultaneous acquisition of 3D FLAIR and SWI data, which produces self-registered images in a clinically feasible time, greatly simplifying the post-processing steps and eliminating interpolation effects. The interleaved time delays in between the FLAIR and SWI modules provide a degree of freedom for further optimization of the image contrast. Experiments in MS patients show the utility of the proposed sequence.

Houshang Amiri ¹, Antoine Meijerman¹, Martijn D. Steenwijk^1,2, Ronald A. van Schijndel³, Frederik Barkhof^2,3, Keith S. Cover¹, and Hugo Vrenken^1,2
1Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands, ²Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands, ³Image Analysis Center, VU University Medical Center, Amsterdam, Netherlands

Interest in measuring brain atrophy in neurodegenerative diseases such as Multiple Sclerosis (MS) and Alzheimer’s disease (AD) is growing. To this end, FreeSurfer and FSL-FIRST are widely used as fully automated algorithms for quantification of the brain volume and volume change in both cross-sectional and longitudinal MRI studies. We have tested reproducibility of these methods in measuring deep gray matter atrophy rates in a group of subjects consisting of healthy aging, mild cognitive impairment and AD. We showed that using longitudinal mode for FreeSurfer and highest number of modes for FIRST provides the best reproducibility that is similar for FreeSurfer and FIRST. 

Loredana Storelli¹, Elisabetta Pagani¹, Maria Assunta Rocca^1,2, Paolo Preziosa^1,2, Antonio Gallo^3,4, Gioacchino Tedeschi^3,4, Maria Laura Stromillo⁵, Nicola De Stefano⁵, Hugo Vrenken⁶, David Thomas⁷, Laura Mancini⁷, Christian Enzinger⁸, Franz Fazekas⁸, and Massimo Filippi^1,2
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ³MRI Center “SUN-FISM”, Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte, Naples, Italy, ⁴I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy, ⁵Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy,⁶Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands, ⁷NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom, ⁸Department of Neurology, Medical University of Graz, Graz, Austria

Aim of the study was to develop a semi-automatic method for the segmentation of hyperintense multiple sclerosis (MS) lesions on dual-echo (DE) PD/T2-weighted scans. DE MRI scans were obtained from 6 different European centers from 52 MS patients with a mean lesion load of 10.3 (± 11.9) ml. The method was based on a region growing approach initialized by manual identification of lesions and a priori information. The segmentation results with the new method showed high accordance with the ground truth and a low misclassification of lesion voxels. Furthermore, operator time required for lesion segmentation was drastically reduced.

Patrick Grabher¹, Claudia Blaiotta², Armin Curt¹, John Ashburner², and Patrick Freund^1,2,3,4
1Spinal Cord Injury Center Balgrist, University of Zurich, Zurich, Switzerland, ²Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom, ³Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, ⁴Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Neurodegeneration and neuroplasticity within the brainstem is poorly understood in patients suffering from spinal cord injury (SCI). We acquired quantitative MRI data of the brainstem using a multi-parameter mapping protocol to assess trauma-induced volumetric and microstructural changes after SCI. We show focal atrophic changes within different subregions of the brainstem in chronic SCI patients and their correlation with clinical outcomes. Neuroimaging biomarkers using quantitative MRI at the brainstem level could be applied to complement clinical assessments during rehabilitation and interventional studies. 

Xuna zhao^1,2, Hongzan Sun³, Jun Xin³, Shanshan Jiang¹, Yansong Zhao⁴, Yi Zhang¹, Dong-Hoon Lee¹, Hye-Young Heo¹, and Jinyuan Zhou^1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Philips Healthcare, Beijing, China, People's Republic of, ³Department of Radiololgy, Shengjing Hospital, Shenyang, China, People's Republic of, ⁴Philips Healthcare, Cleveland, OH, United States

Hybrid PET/MR provides a high resolution anatomical and metabolic imaging approach to evaluate human brain tumors. As a novel molecular MRI technique, CEST MRI has been successfully employed in clinical practice. The combination of [18F]-FDG and CEST images will provide further supplementary information on the study of clinic and molecular mechanism for human brain tumors.  

Maria Aristova¹, Michael Markl², John C Carr², Sameer A Ansari², Can Wu³, and Susanne Schnell^2
1Biomedical Engineering, Northwestern University, Chicago, IL, United States, ²Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States, ³Biomedical Engineering, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

This work compares the utility of time-averaged vs. time-resolved dual-venc 4D flow MRI to look at intracranial blood flow distribution for applications such as evaluation of cerebral arteriovenous malformation (AVM). Time-averaged scans provide larger FOV, no additional time for image reconstruction after the scan and net flow distributions that correlate well with time-resolved scans. 

Mark Oswood^1,2, Bridget Ho³, Aditi Gupta⁴, Todd DeFor⁵, and Nilanjana Banerji^4
1Radiology, HCMC, Minneapolis, MN, United States, ²Radiology, University of Minnesota, Minneapolis, MN, United States, ³John Nasseff Neuroscience Institute, Allina Health, St. Paul, MN, United States,⁴John Nasseff Neuroscience Institute, Allina Health, Minneapolis, MN, United States, ⁵MCC Biostatistics Core, University of Minnesota, Minneapolis, MN, United States

A retrospective analysis of survival after resection of glioblastoma was performed comparing use of intraoperative MRI with conventional surgery.  There was a significant difference in extent of resection, with more gross total resections achieved with iMRI.  There was a significant improvement in overall survival at 6 months with iMRI.  The groups had equivalent survival from 12-36 months.  Younger age was correlated with longer overall survival.

Rossella Canese¹, Giulia Carpinelli¹, Gianmauro Palombelli¹, Caterina Scuderi², Luca Steardo², and Tommaso Cassano^3
1Cell Biology and Neurosciences, Istituto Superiore di Sanita', Roma, Italy, ²Department of Physiology and Pharmacology “Vittorio Erspamer”., University of Rome SAPIENZA, Rome, Italy, ³Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Foggia, Italy

Alzheimer disease (AD) is characterized clinically by progressive cognitive decline, and pathologically by the presence in the brain of senile plaques composed primarily of amyloid-beta peptide and neurofibrillary tangles containing hyperphosphorylated tau protein. Here we investigated the effects ofa naturally occurring amide of ethanolamine and palmitic acid (PEA), abundant in the CNS to contrast the AD phenotype in triple transgene (PS1, APP and Tau) mice model, by in vivo 1H MRI and MRS and histology. Our data indicate that PEA treatment affects brain metabolism as a function of age and that PEA rescues altered molecular pathways that can mimic some traits of AD

Michele Veldsman¹, Amy Brodtmann¹, Graeme Jackson², and Evan Curwood^2
1Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia, ²Epilepsy Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia

Brain atrophy is common after stroke. The extent and pattern of atrophy has not been well investigated and has been limited to localised atrophy and cross-sectional studies, despite network-wide effects of stroke on brain structure and function. We examined correlations in the rate of longitudinal cortical thickness change in stroke patients, compared to healthy age-matched controls. We aimed to investigate whether patterns of neurodegeneration occur in healthy networks as in aging and dementia. We provide evidence of correlations in the rate of cortical atrophy within the DMN suggesting a process of network-based degeneration one year after stroke.

Chien-Yuan Eddy Lin^1,2, Ai-Chi Chen³, David Yen-Ting Chen³, Ying-Chi Tseng³, and Chi-Jen Chen^3
1GE Healthcare, Taipei, Taiwan, ²GE Healthcare MR Research China, Beijing, China, People's Republic of, ³Department of Radiology, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

Pseudo-continuous arterial spin labeling (pCASL) has been recently used for investigating cerebral hemodynamic change on the patient receiving carotid artery stenting (CAS) because it permits repeated measurement of absolute cerebral blood flow in a short interval without MR contrast agent or radioactive material. However, labeling efficiency of pCASL has been proved to be dependent on B₀ inhomogeneity. Labeling position may need to be carefully applied after CAS. The aim of this study was to experimentally determine the optimal labeling position for pCASL with minimal frequency shift caused by stent in exploring cerebral perfusion in the patient with CAS treatment.

Akira Kunimatsu¹, Yasushi Watanabe², Mitsuharu Miyoshi³, Yuichi Suzuki², Kouhei Kamiya¹, Hiroyuki Kabasawa³, Harushi Mori¹, and Kuni Ohtomo^1
1Department of Radiology, The University of Tokyo, Tokyo, Japan, ²Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan, ³Global MR Applications and Workflow, GE Healthcare, Tokyo, Japan

We assessed diagnostic feasibility of vessel wall imaging with MSDE-prepared, 3D T1-weighted variable refocusing flip angle fast spin echo MR imaging (CUBE T1) in differentiation between moyamoya disease (MMD) and intracranial atherosclerotic disease (ICAD), both of which can cause stenosis of the intracranial arteries. MSDE-prepared CUBE T1 enabled correct differentiation in our cohorts and may be helpful to differentiate MMD from ICAD when luminal narrowing is found on conventional brain MRA.

Le He¹, Rui Li¹, Xihai Zhao¹, Shuo Chen¹, and Huijun Chen^1
1Center for BioMedical Imaging Research, Tsinghua University, Beijing, China, People's Republic of

Circle of Willis (CoW) is an important source of collateral blood flow, which may influence the severity of ischemia stroke. However, traditional methods only evaluate the luminal conditions of CoW. This study evaluate the luminal and vessel wall conditions of CoW using bright- and black-blood MRI. We found that most stroke patients have incomplete CoW, and patients with atherosclerotic CoW tends to have larger ischemic infraction. More importantly, the infarction size in stroke patients was significantly associated with integrity&atherosclerosis of CoW, suggesting that the integrity and atherosclerosis of CoW may be a risk factor for stroke severity. 

Huan Yang^1,2, Xuefeng Zhang^1,3, Li Liu¹, Qing Hao⁴, Victor Urrutia⁴, Qin Qin^1,5, Bruce A. Wasserman¹, and Ye Qiao^1
1The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins Hospital, Baltimore, MD, United States, ²Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, People's Republic of, ³Inner Mongolia Autonomous Region People's Hospital, Inner Mongolia, China, People's Republic of, ⁴Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, United States, ⁵F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Although most of strokes occur in asymptomatic patients, most studies have been conducted in symptomatic cohort.  Here we aimed to characterize ICAD in stroke-free participants and compare with stroke patients using 3D high-resolution contrast-enhanced BBMRI.  Nineteen asymptomatic and 15 stroke patients were included and underwent a standardized protocol which contains 3D TOF MRA and pre- and post-contrast 3D BBMRI imaging.  Plaque enhancement was categorized, and morphology and signal-based measurements were compared. The results showed that asymptomatic plaques demonstrated lower contrast-enhancement compared with symptomatic plaques. Contrast-enhancement of ICAD may serve as a marker for plaque stability, providing insight into stroke risk.

Monika Sobczak-Edmans¹, Yu-Chun Lo², Yung-Chin Hsu², Yu-Jen Chen², Fu Yu Kwok¹, Kai-Hsiang Chuang^3,4, Wen-Yih Isaac Tseng^2,5,6,7, and SH Annabel Chen^1,8
1Psychology, Nanyang Technological University, Singapore, Singapore, ²Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, ³The Queensland Brain Institute, The University of Queensland, Brisbane, Australia, ⁴The Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia, ⁵Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan, ⁶Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan, ⁷Molecular Imaging Center, National Taiwan University, Taipei, Taiwan, ⁸Centre for Research And Development in Learning, Nanyang Technological University, Singapore, Singapore

Diffusion spectrum imaging was employed to establish structural connectivity between cerebro-cerebellar regions co-activated during verbal working memory. IFG, IPL, pons, thalamus, superior cerebellum and inferior cerebellum were used as seed points to reconstruct the white matter cerebro-cerebellar circuitry. The reconstructed pathways were examined further to establish the relationship between structural and effective connectivity as well as the relationship between structural connectivity and verbal working memory performance. It was found that structural connectivity is indirectly related to effective connectivity but does not predict it. Additionally, it was demonstrated that the integrity of the ponto-cerebellar tract is an important factor in explaining individual differences in verbal working memory. The findings of the study furthered our understanding of the relationship between structural and functional connectivity and provided insight to the variability in verbal working memory performance. 

James Duffin^1,2, Olivia Sobczyk³, Adrian P Crawley⁴, Julien Poublanc⁴, Paul Dufort³, Lashmi Venkatraghavan⁵, David J Mikulis^3,4, and Joseph A Fisher^1,2,3
1Department of Physiology, University of Toronto, Toronto, ON, Canada, ²Departments of Anaesthesia, University Health Network, Toronto, ON, Canada, ³Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada, ⁴Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, ON, Canada, ⁵Department of Anaesthesia, University Health Network, Toronto, ON, Canada

The patterns of BOLD changes in response to a ramp CO₂ stimulus ranging from hypocapnia to hypercapnia can be classified into four types, based on the two linear slopes fitted to each range.  We describe the physiology underlying the different response patterns using a simple model of two vascular beds competing for the same limited blood supply; deriving the sigmoidal resistance changes in each branch of the model from measured BOLD responses.  We illustrate the use of the model to analyse the BOLD responses in an example patient. 

Yasushi Ogasawara¹, Kuniaki Ogasawara¹, Yuiko Sato¹, Shinsuke Narumi², Makoto Sasaki³, Masakazu Kobayashi¹, Shunrou Fujiwara¹, Kenji Yoshida¹, Yasuo Terayama², and Akira Ogawa^1
1Department of Neurosurgery, Iwate Medical University, Morioka, Japan, ²Department of Neurology and Gerontology, Iwate Medical University, Morioka, Japan, ³Institute for Biomedical Sciences, Iwate Medical University, Morioka, Japan

Preoperative 2D MR carotid plaque imaging can assess plaque vulnerability. It may allow improved risk stratification for patients considered for CEA and may be associated with development of MES during CEA. On the other hand, it is unclear what position of high signal intensity in the plaque, especially at the position showing maximum stenosis or maximum signal intensity, is deeply associated with MES, and it is difficult to validate it by the 2D plaque imaging. The aim of the present study was to determine where in the plaque is deeply associated with development of MES on TCD during CEA in carotid artery stenosis, using 3D-FSE T1W plaque imaging.

Huaiqiang Sun¹, Haoyang Xing¹, Jiayu Sun¹, Lu Ma², Ji Bao³, Youjin Zhao¹, and Qiyong Gong^1
1Huaxi MR Research Center, Department of Radiology., West China Hospital, Chengdu, China, People's Republic of, ²Department of Neurosurgery, West China Hospital, Chengdu, China, People's Republic of, ³Laboratory of Pathology, West China Hospital, Chengdu, China, People's Republic of

A semi-automatic workflow, which can be done within one hour and need minimal manual intervention, was proposed for constructing printable 3D models for cerebrovascular surgical planning based on MR angiography and CT data. The constructed models were consistent with the findings of MR angiography and have the potential to help surgeons to rehearse the operation beforehand and reduce operative risk.

Lukas Mario Gottwald¹, Rainer Schneider¹, and Josef Pfeuffer^1
1MR Application Development, Siemens Healthcare, Erlangen, Germany

In clinical 3T imaging, gradient-echo-based sequences often suffer from signal loss induced by patient-specific susceptibility artifacts. To tackle this problem, a proposed local signal recovery z-shim method using parallel transmission was implemented for a clinical setup. The approach was further extended by an automated slice-specific delay-time calculation to ensure user-friendly operation as well as maximal signal gain in artifact regions. Studies in humans were carried out using commonly used GRE and EPI sequences. Signals could be nearly fully recovered in artifact regions; tSNR gain maps for EPI time series showed an increase up to 148%.

Lori Jordan¹, Melissa Gindville¹, Allison Scott¹, Meher Juttukonda¹, Megan Strother¹, Adetola Kassim¹, Sheau-Chiann Chen¹, Hanzhang Lu², Sumit Pruthi¹, Yu Shyr¹, and Manus J. Donahue^1
1Vanderbilt University Medical Center, Nashville, TN, United States, ²Johns Hopkins University, Baltimore, MD, United States

The goal of this work is to apply hemo-metabolic MRI to evaluate relationships between oxygen extraction fraction (OEF), cerebral blood flow (CBF), and clinical impairment in adults with sickle cell anemia (SCA). Healthy (n=11) and sickle cell anemia (n=34) participants received neurological evaluation, head/neck-angiography, structural-MRI, CBF-weighted-MRI, and T2-relaxation-under-spin-tagging (TRUST)-MRI.  CBF and OEF were elevated (P<0.05) in SCA relative to control participants; OEF (P<0.0001) but not CBF was increased in SCA participants with higher clinical impairment. Data provide support for TRUST-MRI being able to quickly and noninvasively detect elevated OEF in SCA participants with high levels of clinical impairment.

Yasutaka Fushimi¹, Tomohisa Okada^1,2, Akira Yamamoto¹, Takayuki Yamamoto¹, Aurelien Stalder³, Michaela Schmidt³, Yutaka Natsuaki³, and Kaori Togashi^1
1Kyoto University Graduate School of Medicine, Kyoto, Japan, ²Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan, ³Siemens, Erlangen, Germany

Sparse TOF has demonstrated the potential to accelerate TOF MRA. We conducted comparison study targeting patients with cerebral aneurysms to check the clinical relevance of evaluation of aneurysms on Sparse TOF 3X, 5X and TOF with parallel imaging (PI TOF). MIP images of patients with cerebral aneurysms were blindly evaluated by one neuroradiologist, and the sum of grades were compared among Sprase TOF 3X, 5X and PI-TOF 3X. Sparse TOF 3X and 5X were reconstructed with clinically acceptable time, and cerebral aneurysms were visible in both Sparse TOF 3X and 5X with equivalent quality as PI TOF.

Tora Dunås¹, Anders Wåhlin^1,2, Khalid Ambarki^1,3, Laleh Zarrinkoob⁴, Jan Malm⁴, and Anders Eklund^1,2,3
1Department of Radiation Sciences, Umeå University, Umeå, Sweden, ²Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden, ³Centre for Biomedical Engineering and Physics, Umeå University, Umeå, Sweden, ⁴Department of Clinical Neuroscience, Umeå University, Umeå, Sweden

The cerebral arterial system is complex with large inter-individual spatial variations, which are potentially challenging for automatic methods. The objective of this work was to construct an artery specific probabilistic atlas of 16 large cerebral arteries, based on 168 subjects, and to investigate if the regional specificity of vascular branches was sufficient to permit atlas based arterial labeling. Voxels of the arterial centerlines was labeled according to the highest probability at the corresponding location in the atlas. The rate of correctly labeled voxels was over 80% for all arteries, which should be sufficient to permit atlas based arterial labeling.

Giorgio Conte^1,2, Claudia Cesaretti¹, Giana Izzo¹, Cecilia Parazzini¹, and Andrea Righini^1
1Radiology and Neuroradiology, Children's Hospital V. Buzzi, Milan, Italy, ²Radiology Institute, University of Milan, Milan, Italy

Ganglionic eminence (GE) is the main proliferative structure of the ventral telencephalon and contributes to GABA-ergic cortical interneuron population; GE imaging characterization in normal and abnormal conditions is poor. After searching a 3500 cases fetal MR database, we illustrate normal GE features, its abnormalities and its possible associations. GE malformations are divided: 1) bilateral symmetric cavitations as inverted C shape separating GE from parenchyma; 2) GE volume increase associated or not with the above mentioned cavitation. About half of cases are associated with micro-lissencephaly, the others with minor-moderate anomalies. As group apart are presented clastic GE lesions, featuring haemorrhagic changes.

Lianqing Zhang¹, Xingyu Hu¹, Shiguang LI², Lei Li ¹, Lizhou Chen¹, Qi Liu¹, Lu Lu¹, Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), radiology department, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²radiology department, The First People's Hospital of Zunyi, Zunyi, China, People's Republic of

We analysis hippocampal subfields volume changes in a relatively large sample of adult patients with post-traumatic stress disorder and same stressor event survivors using an automatically segmentation protocol. Our findings provided evidence that the responsive change of hippocampus after stress which cause cellular edema or at a early stage of the disorder. The second find is the difference between genders referring to the role of hippocampus in PTSD etiology. Male patients seem to be more likely affected in right hippocampus while in female patients, left hippocampus seems contributed more.

Sang-Young Kim^1,2, Bruce Cohen³, Scott Lukas⁴, Cagri Yuksel², Dost Ongur², and Fei Du^1,2
1McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA, United States, ²Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, United States, ³Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA, United States, ⁴Behavioral Psychopharmacology Research Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA, United States

In this work, we demonstrated the feasibility of 31P MRS-based in vivo intracellular redox state quantification at 4 T. We applied this novel method to investigate oxidative stress in the frontal lobe of chronic and first-episode SZ as well as first-episode BD patients. We found evidence for striking Rx reductions in SZ, with every chronic SZ patient showing an Rx of at least one standard deviation below the control mean. Rx reduction was of even greater magnitude among first-episode SZ patients. This study illustrates the power of examining in vivo brain redox dysregulation (measured as Rx) in psychiatric disorders.

Wenjing Zhang¹, Wei Deng², Siyi Li¹, John Sweeney³, Qiyong Gong¹, and Su Lui^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ³Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States

A simultaneous multi-slice multiband EPI sequence, which could significantly increase temporal resolution for the fMRI scanning, was adopted to investigate the dynamic functional connectivity in the schizophrenia patients with auditory hallucinations. We found that, relative to traditional static functional connectivity calculation, dynamic analysis evaluated with multiband EPI provides much more information, including more widespread aberrant functional connectivity maps across different states and their temporal variability over time. The expanded information may help to give better insight into the pathological processes and subsequently reveal the spontaneous model of affected networks in schizophrenia.  

Subechhya Pradhan¹, Laura M. Rowland², S. Andrea Wijtenburg², Stephanie Korenic², Sarah Nosinger², L. Elliot Hong², and Peter B. Barker^1,3
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States, ³Radiology, Kennedy Krieger Institute, Baltimore, MD, United States

Imbalance in the glutamatergic system is implicated in the pathophysiology of schizophrenia. Various previous MRS studies have reported altered levels of glutamate and/or glutamine in schizophrenia, however most of these studies have been performed at 3T or lower where separation from Glu from Gln is challenging, and few have looked at correlations with disease severity or cognitive impairment. The purpose of this study was to investigate neurochemical differences in participants with and without schizophrenia using high-resolution 7T MRS in multiple brain regions, and to exam correlations with measures of cognitive impairment, function and symptom severity.

Nicolas Kunz¹, Alexandre Bacq², Jocelin Grosse², Rolf Gruetter^1,3, and Carmen Sandi^2
1CIBM-AIT, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland, ²Laboratory of Behavioral Genetics, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland, ³Department of Radiology, University of Geneva and Lausanne, Geneva, Lausanne, Switzerland

Schizophrenia is a severe mental disorder that afflicts 1% of the world’s population. However, the cause of this disorder remains unknown. Increasing evidence points toward a neurodevelopmental mechanism, which implicates genes involved in neuronal proliferation, migration, or synapse formation. We investigate microstructural changes by ex-vivo diffusion MRI in PSA-KO mice brain. Trends of microstructural alterations were visible in a few fiber tracts such as ST, ST-post, AC and FX. These preliminary results suggest that altered plasticity during development of the PSA-KO mice, presenting schizophrenic like phenotype and altered sociability, creates long term effects and structural alterations depicted by dMRI.

Lu Liu¹, Yuan Xiao¹, Wenjing Zhang¹, and Su Lui^2
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan university, Chengdu, China, People's Republic of

Using SVM to characterize structural and functional pattern implicated in antipsychotic-naive schizophrenia  to predict the response of anti-psychotic treatment and also to examine the structural neuroanatomy and functional activity . And revealed that anatomical and functional changes revealed by Multi-modality MRI in first-episode schizophrenia patients before treatment showed the potential in predicting the one year treatment response, which could help psychiatrists to make treatment strategy for individual patient in future.

Andrei Valerievich Manzhurtsev¹, Maxim Vadimovich Ublinskii^1,2, Irina Sergeevna Lebedeva³, Tolibjon Abdullaevich Akhadov², Petr Evgenevich Menshchikov⁴, and Natalia Alexandrovna Semenova^1,2,4
1Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Moscow, Russian Federation, ²Radiology, Scientific Research Institute of Children's Emergent Surgery and Trauma, Moscow, Russian Federation, ³Scientific Centre of Mental Health, Moscow, Russian Federation, ⁴Semenov Institute of Chemical Physics of Russian Academy of Sciences, Moscow, Russian Federation

³¹P MRS in the period of neuroactivation allows direct analysis of metabolic response on energy consuming processes. In this study we revealed decreased creatine kinase system response in visual cortex of early stage schizophrenia patients in the period of videostimulation: while PCr in normal activated cortex is reduced for ATP regeneration during activation, no PCr decrease was observed in patients. The data obtained allowed to offer a new neuronal metabolism scheme in response to stimulation at early stage of schizophrenia.

Greg D Parker¹, George J.A. Evans², and Derek K Jones^1,3
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ²School of Medicine, Newcastle University, Newcastle, United Kingdom, ³Neuroscience and Mental Health Research Institute (NMHRI), School of Medicine, Cardiff University, Cardiff, United Kingdom

Changes in the size and shape of white matter tracts are known to be associated with the onset or progress of various brain disorders. Common techniques for characterising tract shape include measuring cross sectional area or thickness^1-3, Fourier descriptors⁴ and measures of streamline dispersion⁵. Here we present a novel principal component analysis (PCA)-based method and demonstrate two ways in which those representations may be used to examine inter-group differences in tract shape. As an example, we compare 30 first-episode psychosis patients with age/sex matched controls and find significant shape differences in the genu of the callosum.

Chandan Shah¹, Wenjing Zhang¹, Yuan Xiao², Li Yao², Xin Gao², Lu Liu², Jieke Liu², Siyi Li², Qiyong Gong², and Su Lui^2
1Radiology, Sichuan University, Chengdu, China, People's Republic of, ²Chengdu, China, People's Republic of

Current study provides an insight about the brain morphological changes of first episode schizophrenia patients at drug-naive state and after antipsychotic treatment. Our study reveals that GM changes in frontal, temporal and insular regions are the fundamental regions of pathologic GM changes in first-episode schizophrenia irrespective of antipsychotic medication. This common pattern of GM changes in first episode schizophrenia patients with and without antipsychotics suggest the anatomical deficits involved in the fronto-temporal and limbic regions are likely to be the trait- instead of state-related changes at the early course of illness in schizophrenia. Until now only assumptions have been made about the potential effects of antipsychotics rather than making a strong statement due to lack of proper investigation methods and also due to difficulty in gaining access to a satisfactory number of drug naïve and medicated patients group of the same age. We therefore hope this study would be helpful in providing important information about the pathology of the schizophrenic brain after the early course of treatment with antipsychotics.

Pui Wai Chiu¹, Queenie Chan², Sai-yu Lui³, Karen Shee Yueng Hung³, Raja Rizal Azman Raja Aman⁴, Raymond Chor Kiu Chan⁵, Pak Chung Sham⁶, Eric Fuk Chi Cheung³, Richard A Edden⁷, and Henry Ka Fung Mak^1
1Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, ²Philips Healthcare, Hong Kong, Hong Kong, Hong Kong, ³Institute of Mental Health, Castle Peak Hospital, Hong Kong, Hong Kong, ⁴Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia, ⁵Neuropsychology and Applied Cognitive Neuroscience Laboratory, Chinese Academy of Sciences, Beijing, China, People's Republic of, ⁶Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong, ⁷Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, United States

Gamma-amino butyric acid (GABA) is thought to play an important role in the pathophysiology of schizophrenia. The anterior cingulate cortex (ACC) has been reported to exhibit functional and morphological abnormalities in schizophrenic patients compared to healthy controls(HC). In this pilot study, absolute concentrations of GABA([GABA]_abs) and Glx([Glx]_abs)  were measured in the ACC of 9 schizophrenic patients and 14 HC at 3.0T. Significant lower [GABA]_abs level in ACC of schizophrenic patients might provide evidence of abnormalities in GABAergic neurotransmission in schizophrenia. Significant positive correlation between [Glx]_abs and positive symptoms subscale might indicate Glx level is specific for positive symptoms in ACC.

Subechhya Pradhan¹, Anouk Marsman¹, Rebecca Ward², Candice Ford², Ashley Lloyd², David Schretlen^1,2, Akira Sawa², and Peter B. Barker^1,3
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Radiology, Kennedy Krieger Institute, Baltimore, MD, United States

Imbalance in glutamatergic systems is implicated in the pathophysiology of psychosis. The purpose of this study was to assess differences in metabolite levels between subjects with a first episode of psychosis (FEP) and healthy controls, and to study correlations between metabolites and measures of disease severity, including neuropsychological scales, positive and negative symptoms.

Florian Schubert¹, Ralf Mekle¹, Johanna Balz², Julian Keil², Yadira Roa Romero², Bernd Ittermann¹, Jürgen Gallinat³, and Daniel Senkowski^2
1Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany, ²Charité Universitätsmedizin Berlin, Berlin, Germany, ³Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Findings of deviant glutamate (Glu) and glutamine (Gln) levels in brain of patients support the glutamate hypothesis of schizophrenia. Thickness and volume of the left superior temporal gyrus (STG) are established endophenotypes of schizophrenia. We quantified glutamatergic metabolites using proton MRS with SPECIAL in the left STG of schizophrenic patients and controls, and investigated the relationships between Glu and personality traits. Glu was significantly higher in patients than in controls, Gln likewise but with a weak trend only. Glu predicted neuroticism in patients. Our results suggest dysfunctional glutamatergic neurotransmission in STG and confirm widespread Glu increases in cortical regions in schizophrenia.

Ravi Prakash Reddy Nanga¹, David R. Roalf², Petra Rupert², Megan Quarmley², Hari Hariharan¹, Mark Elliott¹, Raquel E. Gur², Paul J. Moberg², Ravinder Reddy¹, and Bruce I. Turetsky^2
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

In this glutamate Chemical Exchange Saturation Transfer (GluCEST) study, typically developing individuals and youth at clinical high risk for psychosis exhibit subtle, but significant, abnormalities in brain glutamate, similar to patients with schizophrenia in the entire cortical area. GluCEST technique holds distinct promise for understanding neurodevelopmental contributions to schizophrenia pathophysiology.

Ivan I. Kirov^1,2, Emma J. Meyer^1,2, Assaf Tal³, Matthew S. Davitz^1,2, Dolores Malaspina^4,5, and Oded Gonen^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ⁴Psychiatry, New York University School of Medicine, New York, NY, United States, ⁵Institute for Social and Psychiatric Initiatives (InSPIRES), New York University Langone Medical Center, New York, NY, United States

The objective of this study was to test the hypothesis that schizophrenia patients’ hippocampi are metabolically different from healthy controls’. Twenty-four patients and seven controls were studied with proton MR spectroscopic imaging at 3 T. Hippocampal volumes were also obtained. The findings were increased choline concentration in patients' hippocampi compared with controls, but no statistically significant changes in n-acetyl-aspartate or total creatine. While contrary to previous (mostly single-voxel) proton MR spectroscopy studies, these findings are nevertheless consistent with neuropathology reports of neither gliosis nor net neuronal loss. Bilateral hippocampal volume was 10% lower in the patients, consistent with previous reports.

Bo Tao¹, Yuan Xiao¹, Lu Liu¹, Li Yao¹, Wenjing Zhang¹, and Su Lui^1
1Radiology, West China Hospital of SiChuan University, Chengdu, China, People's Republic of

In summary, the present study provided evidence that single nucleotide polymorphisms(SNPs) on  the major histocompatibility (MHC) relate with cortical thickness deficits in several regions,which support the critical role of immune system in the pathology of schizophrenia via modulation the development of the cerebral cortical structure.

Merry Mani¹, Nancy Andreasen¹, and Vincent Magnotta^1
1University of Iowa, Iowa City, IA, United States

  Schizophrenia is a psychiatric illness characterized by failure of functional integration. To shed light on the underlying pathophysiology, the complex networks of the brain have to be studied comprehensively. This study used network analysis tools to study the topological features of the brain in schizophrenia. Using diffusion tensor imaging, we generated the graph network of schizophrenia patients and controls. We defined 68 cortical regions as nodes and used streamlines derived from deterministic fiber tracking to define the edges of the graph. A permutation testing was used to test differences between topological measures derived from the graphs of schizophrenia patients and controls.

yadi li¹, Haibo Dong¹, Feng Li¹, Gaoyan Wang¹, Wenwen Shen², Wenhua Zhou², Jianbing Zhang², Longhui Li², and Chaogan Yan^3
1The Affiliated Ningbo Medical Treatment Center Lihuili Hospital of Ningbo University, Ningbo, China, People's Republic of, ²Ningbo Addiction Research and Treatment Center, Ningbo, China, People's Republic of, ³Institute of psychology, Chinese academy of sciences, Beijing, China, People's Republic of

This study detected microstructural changes of amygdala and hippocampus in methamphetamine(METH) users with psychosis by analyzing FA index on diffusion weighted imaging, while these users presented no evident volume reduction in these 2 structures. These 2 structures play a vital part in METH psychosis

Chien-Hung Lu¹, Yu-Jen Chen², Yu-Chun Lo², Yu-Chun Hsu², Susan Shur-Fen Gau^3,4, and Wen-Yih Isaac Tseng^2,4
1School of Medicine, National Taiwan University, Taipei, Taiwan, ²Institute of Medical Device and Imaging, National Taiwan University, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan, ⁴Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

The corpus callosum (CC) has been the most investigated white matter tract in autismspectrum disorder (ASD). However, whether the development of the CC is altered in ASD is not clearly identified. In this study, we performed diffusion spectrum imaging using tract specificanalysis to measure the generalized fractional anisotropy of 16 segments of the CC. A GFA–age hyperbolic model was applied to test the age effect. The CC connecting bilateral temporal lobes was signficantly different between ASD and TD. Our results identify the unique time trajectory of the CC in ASD.

Douglas C Dean III¹, Nicholas Lange², Brittany Travers¹, Nagesh Adluru¹, Do Tromp¹, Daniel Destiche¹, Abigail Freeman¹, Danica Samsin¹, Brandon Zielinski³, Molly Prigge³, P.T. Fletcher³, Jeffery Anderson³, Erin Bigler⁴, Janet Lainhart¹, and Andrew Alexander^1
1Waisman Center, University of Wisconsin-Madison, Madison, WI, United States, ²McLean Hospital, Boston, MA, United States, ³University of Utah, Salt Lake City, UT, United States, ⁴Brigham Young University, Provo, UT, United States

To date, the heterogeneity of neuroimaging findings has made it challenging to identify specific brain-related phenotypes within autism spectrum disorder (ASD). In particular, a quantitative index of individual deviation across a set of brain measurements may be informative for constructing distributions of brain variation and identifying individuals who may or may not have abnormal brain structure. To this end, we investigated the use of the Mahalanobis distance to characterize multidimensional brain measures in individuals with and without ASD and to demonstrate that patterns of brain features distinguishing individuals with ASD are multidimensional and likely encompass differing cortical and sub-cortical characteristics.

Alessandra Retico¹, Ilaria Gori^1,2, Alessia Giuliano^1,3, Piernicola Oliva^1,2, Michela Tosetti⁴, Filippo Muratori^3,4, and Sara Calderoni^4
1National Institute of Nuclear Physics, Pisa, Italy, ²University of Sassari, Sassari, Italy, ³University of Pisa, Pisa, Italy, ⁴IRCCS Stella Maris Foundation, Pisa, Italy

Binary classifiers are widely used to analyze brain MRI features and to identify useful biomarkers of pathology. Strong challenges arise when dealing with extremely heterogeneous conditions such as Autism Spectrum Disorders (ASD). We propose the use of the One-Class Classifier (OCC) method that, in contrast to two-class classification, is based on the description of the positive class only. A test of similarity of new cases to the positive examples is then performed, and they are eventually considered as outliers. The application of OCC to Freesurfer-based brain MRI features identified a specific endophenotype in young children with ASD.

Judith A. Gadde¹ and John-Paul J. Yu^1,2
1Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ²Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States

Autism spectrum disorder (ASD) is a complex genetic neurodevelopmental disorder. Differential expression patterns, splice-variants, and mutations in Neurexin1 (Nrxn1) have been implicated in the neurodevelopment of ASD. New targeted genome editing technologies have yielded the first cogent genetic animal models of ASD with animals harboring biallelic deletions of Nrxn1, allowing for the assessment of gene-specific perturbations in white matter composition and organization. Interrogating changes in brain structure attributable to a specific genetic allele is the first step towards the development and validation of an objective imaging biomarker, which can contribute to the diagnosis of ASD. 

Yi-Chun Liu¹, Vincent Chin-Hung Chen², Hse-Huang Chao³, Ming-Chou Ho⁴, and Jun-Cheng Weng^1,5
1Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan, ³Tiawan Center for Metabolic and Bariatric Surgery, Jen-Ai Hospital, Taichung, Taiwan, ⁴Department of Psychology, Chung Shan Medical University, Taichung, Taiwan,⁵Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Since there is more and more delicious food in our daily life, people cannot resist the attraction to food. Therefore, obesity has become an important issue in modern society. Previous studies used food pictures to stimulate obese patients and used functional MRI to find the brain regions with increased activity. However, few studies mentioned about particular brain structure changes in obese patient. Noninvasive diffusion tensor imaging (DTI) are able to observe the water diffusion in the brain on the microscopic level for the early detection of white matter structural changes. Therefore, we used DTI to find the differences of brain structures between obese patients and healthy controls. The correlation between clinical and the DTI indices were also calculated and discussed. The clinical indices included body mass index (BMI), and measures of anxiety and depression.

Xiang He¹, Kenneth Wengler^1,2, Ananth Narayanan³, Chuan Huang¹, Christine DeLorenzo³, Ramin Parsey³, Mark Schweitzer¹, and Andrew Goldfine^3
1Radiology, Stony Brook University School of Medicine, Stony Brook, NY, United States, ²Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, ³Psychiatry, Stony Brook University School of Medicine, Stony Brook, NY, United States

Five post-stroke apathy patients underwent simultaneous ¹⁸F-FDG-PET/MRI to determine brain metabolic rates. PET data was used to determine whole brain metabolic rate of glucose (MR_Glu). Quantitative BOLD and arterial spin labeling MRI was used to determine cerebral metabolic rate of oxygen (CMRO₂). Metabolic rates were compared for the two modalities to determine useful information associated with post-stroke apathy. The prefrontal cortex showed decreased metabolic rates for both CMRO₂ and MR_Glu potentially indicating apathy. MR qBOLD-derived CMRO₂ measurements demonstrated good correlation with PET ¹⁸F-FDG metabolism, providing strong support for its adoption as a non-invasive mapping of brain metabolism in patients with post-stroke apathy. 

Lianping Zhao¹, Ying Wang¹, Yanbin Jia¹, Shuming Zhong¹, Yao Sun¹, Zhifeng Zhou¹, and Li Huang^1,2
1Jinan university, Guangzhou, China, People's Republic of, ²Guangzhou, China, People's Republic of

Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in cerebellum between BD and UD. Patients with BD (n = 35) and UD (n = 30) during a depressive episode as well as 40 healthy controls underwent diffusional kurtosis imaging (DKI) and three dimensional arterial spin labeling (3D ASL). The DKI parameters including mean kurtosis (MK), axial kurtosis(Ka), radial kurtosis (Kr),fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) and 3D ASL parameters (i.e. cerebral blood flow) was measured by using regions-of-interest (ROIs) analysis in the superior cerebellar peduncles(SCP), middle cerebellar peduncles (MCP) and dentate nuclei (DN) of cerebellum. Patients with UD exhibited significant differences from controls for DKI measures in bilateral SCP and MCP and cerebral blood flow (CBF) in bilateral SCP and left DN. Patients with BD exhibited significant differences from controls for DKI measures in the right MCP and left DN and CBF in the left DN. Patients with UD showed significantly lower MD values compared with patients with BD in the right SCP. Correlation analysis showed there were negative correlations between illness duration and MD and Dr values in the right SCP in UD, and negative correlations between illness duration and CBF in bilateral SCP in BD. Our findings provide new evidence of microstructural changes in cerebellum in BD and UD. The two disorders may have overlaps in microstructural abnormality in MCP and DN during the depressive period. Microstructural abnormality in SCP may be a key neurobiological feature of UD.

Deborah Xiu-Ning Lin¹, Shu-Wei Chu¹, Ming-Chou Ho², and Jun-Cheng Weng^1,3
1Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Psychology, Chung Shan Medical University, Taichung, Taiwan,³Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Betel nut is the seed of the betel palm, which grows in the tropical or subtropical regions, especially in Taiwan, India, China and parts of east Africa. It has been confirmed that chewing betel nuts can be addicted to it and is also carcinogenic to humans. Chewing betel nuts lead to a greatly increased risk of developing a range of serious diseases, including oral and esophagus cancers. In Taiwan, 88% of people who were diagnosed to oral cancer have the habit of chewing betel nuts, but very few researches studied on how chewing betel nuts effects brian structure. Therefore, in this study we tried to find out the structural volume and shape changes in the brain between betel nut chewers and healthy controls with voxel-based morphometry (VBM) and vertex-wise shape analyses. In addition, the relationship between brain structural volume size and implicit attitude or inhibitory control were also discussed.

Hu Cheng¹, Derek Kellar¹, Ulrike Dydak^2,3, Peter Finn¹, Allison Lake ¹, Shalmali Dharmadhikari^2,3, George Rebec ¹, and Sharlene Newman^1
1Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States, ²School of Health Sciences, Purdue University, West Lafayette, IN, United States, ³Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States

Evidence indicates that glutamate neurotransmission plays a critical role in alcohol and other substance addiction. This study investigated the dynamic change of glutamate level elicited by alcohol cues in individuals with alcohol use disorder (AUD). Both the absolute value of glutamate concentration and its ratio to total creatine measured decreased significantly for AUD subjects after they viewed the pictures of alcoholic beverages. A high correlation (r = -0.90) between baseline glutamate level and alcohol problem counts was observed for AUD subjects. This cue induced decrease of glutamate is not a direct translation from animal studies. 

Harald Kugel¹, Udo Dannlowski^2,3, Dominik Grotegerd², Ronny Redlich², Nils Opel ², Katharina Dohm², Dario Zaremba², Anne Groegler², Juliane Schwieren², Thomas Suslow⁴, Patricia Ohrmann ², Jochen Bauer^1,2, Axel Krug³, Tilo Kircher³, Christa Hohoff², Katharina Domschke⁵, Andreas Jansen³, Pienie Zwitserlood⁶, Markus Heinrichs^7,8, Volker Arolt², Walter Heindel¹, and Bernhard T. Baune^9
1Department of Clinical Radiology, University of Muenster, Muenster, Germany, ²Department of Psychiatry, University of Muenster, Muenster, Germany, ³Department of Psychiatry, University of Marburg, Marburg, Germany, ⁴Department of Psychosomatics and Psychotherapy, University of Leipzig, Leipzig, Germany, ⁵Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany,⁶Department of Psychology, University of Muenster, Muenster, Germany, ⁷Department of Psychology, University of Freiburg, Freiburg, Germany, ⁸Freiburg Brain Imaging Center, University of Freiburg, Freiburg, Germany, ⁹School of Medicine, Discipline of Psychiatry, University of Adelaide, Adelaide, Australia

Oxytocin is a pro-social and anxiolytic neuropeptide, especially if the G-allele of a common polymorphism (rs53576) in the oxytocin receptor gene is present. Recent studies suggest, however, a detrimental role of this allele in the context of childhood maltreatment. Structural MRI data show reduced gray matter volumes of the ventral striatum, fMRI shows increased amygdala responsiveness associated with increased CTQ (maltreatment) score. Thus for individuals with adverse childhood experiences the G-allele may be a vulnerability factor.

Min-Hee Lee¹, Yoon Ho Hwang¹, Areum Min¹, Dong Youn Kim¹, Bong Soo Han², and Hyung Suk Seo^3
1Department of Biomedical Engineering, Yonsei University, Wonju, Korea, Republic of, ²Department of Radiological Science, Yonsei University, Wonju, Korea, Republic of, ³Department of Radiology, Korea University Ansan Hospital, Ansan, Korea, Republic of

Although Internet addiction (IA) has been increasingly considered as a serious public health issue for adolescents, its neurobiological mechanisms remain poorly understood. Therefore, new biomarkers are needed to understanding IA. Using diffusion tensor images for IA and healthy adolescents, we analyzed brain network to reveal structural alterations in brain of IA adolescents. IA adolescents showed increase of regional efficiency in bilateral superior orbitofrontal cortex, right rectus and parahippocampal gyrus. Severity of IA is correlated with regional efficiency of brain regions which showed differences between groups. The brain network analysis can be used to disclose potential functional deficits in IA.

Kouhei Kamiya¹, Naohiro Okada², Yuichi Suzuki³, Ryusuke Irie¹, Takatoshi Kubo¹, Yudai Nakai⁴, Yasumasa Nippashi¹, Daisuke Koshiyama², Kentaro Morita², Kingo Sawada², Yoshihiro Satomura², Shinsuke Koike^2,5, Harushi Mori¹, Akira Kunimatsu¹, Kiyoto Kasai², and Kuni Ohtomo^1
1The Department of Radiology, The University of Tokyo, Tokyo, Japan, ²The Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan, ³The Department of Radiological Technology, The University of Tokyo Hospital, Tokyo, Japan, ⁴The Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan, ⁵Of?ce for Mental Health Support, Division for Counseling and Support, The University of Tokyo, Tokyo, Japan

This study aimed to investigate the brain microstructural alteration in patients with major depressive disorder (MDD) using neurite orientation dispersion and density imaging (NODDI). Nineteen MDD patients and 13 controls were involved. The TBSS analyses revealed significant increase in orientation dispersion index (ODI) in patients with MDD, distributed in bilateral frontal lobes and right occipital lobe, right internal capsule, bilateral thalamus and hypothalamus, right nucleus accumbens, and midbrain tegmentum, suggesting involvement of the reward circuit. The neurite density was not significantly altered, arousing interest on further study focusing on treatment response, whether the ODI increase is reversible or not.

Lei Li¹, Xinyu Hu¹, Du Lei¹, Xiaoqi Huang¹, and Qiyong Gong^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of

The current study used voxel-based morphometry (VBM)-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) algorithm to investigate the gray matter abnormalities in drug-naïve first-episode pediatric patients with posttraumatic stress disorder (PTSD) using high resolution structural MRI. Meanwhile, we investigated the association between altered neural correlates and symptom severity as measured by clinician-administered PTSD scale (CAPS) and PTSD checklist (PCL) scores with the age as a covariate. The current study provided the preliminary evidence that the intrinsic abnormalities of neural correlates in pediatric PTSD patients were mainly in fear circuit and default mode network.

Xinyu Hu¹, Xi Yang², Yanchun Yang², Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of

We analysis whole brain connectivity in a relatively large sample of drug-naive patients with obsessive-compulsive disorder (OCD) using a novel graph-theory approach known as functional connectivity strength (FCS) to identify brain regions displaying high-degree centrality of connectivity. Based on the new approach of FCS, our findings demonstrated obvious significant hyperactivity of default mode network (DMN) in OCD patients at resting state. Furthermore, our results provided evidence that besides the prevailing model of cortical–striatal–thalamic–cortical circuits in OCD, the disequilibrium between the DMN and the salience network (SN) might be associated with the pathophysiology of OCD.

Ziqi Chen¹, Mingrui Xia², Jia Liu¹, Zhiyun Jia^1,3, Xin Xu^1,4, Weihong Kuang⁴, Yong He², and Qiyong Gong^1,5
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China, People's Republic of, ³Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ⁴Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ⁵Department of Psychology, School of Public Administration, Sichuan University, Chengdu, China, People's Republic of

The underlying neural correlates of suicide attempts in major depressive disorder (MDD) at the connectivity or circuit level remains incompletely understood. Therefore, we utilized a graph-theory approach—functional connectivity strength (FCS) to identify resting-state functional connectivity alterations of whole-brain networks in MDD patients with a history of suicide attempts. Relative to healthy controls, two MDD patient groups (attempters and non-attempters) showed overlapping reduced FCS in the middle and inferior occipital gyrus (IOG), insula, superior temporal gyrus, thalamus and limbic regions, while attempters showed more decreased FCS in right insula and left IOG. The depression severity was positively correlated with FCS in right thalamus in suicide attempters. Disconnection of the insula and IOG could be biological correlates of impaired decision making and emotional information processing in MDD patients with a history of suicide attempt. 

Victoria X Wang¹, Caroline Menard², Cheuk Ying Tang³, Frances Marks¹, Johnny C Ng¹, Lazar Fleysher¹, Zahi A Fayad¹, and Scott Russo^2
1Radiology, Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, United States, ²Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ³Radiology & Psychiatry, Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, United States

We studied functional and structural connectivity in a stress susceptible and resilient mouse model using rsfMRI and DTI. We also investigated the integrity of the Blood Brain Barrier using Gd-DTPA. We found hyperactivity in the susceptible mice which had also several regions in the brain with compromised BBB. We also detected increased structural connectivity in the resilient mice.

Lihua Qiu^1,2, Mingrui Xia³, Yong He³, and Qiyong Gong^2
1Radiology, The Second People's Hospital of Yibin, Yibin, China, People's Republic of, ²West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ³Beijing Normal University, Beijing, China, People's Republic of

Neuroimaging studies have shown that MDD is accompanied by functional abnormalities in amygdala and related connections; yet, little is known about amygdala subregion dynamic functional connectivity alterations of the whole-brain networks in MDD patients. In this work, general linear model analysis were used to assess the between-group differences of amygdalar subregion dynamic functional connectivity alterations in MDD patients. We found the altered amygdaloid projection were mainly in brainstem, cerebellum, thalamus, temporal and orbital cortical areas. These areas belong to limbic-thalamo-cortical circuitry which play important role in MDD and may associated with the impaired emotional modulation ability in MDD.

Andreas Hock^1,2, Jutta Ernst², Anke Henning^1,3, Erich Seifritz², Heinz Boeker², and Simone Grimm^2,4
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ⁴Department of Psychiatry, Charité, Berlin, Germany

Proton magnetic resonance spectroscopy (¹H-MRS) was used to test whether patients with major depressive disorder have increased glucose and lactate levels in the pregenual anterior cingulate cortex (PACC) compared to healthy controls. Therefore, forty healthy and depressed participants spectra were acquired from the PACC using a maximum echo JPRESS protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate.

Elisa Kallioniemi^1,2, Mervi Könönen^1,3, Juhana Hakumäki³, Esa Mervaala¹, Heimo Viinamäki⁴, Ritva Vanninen³, and Minna Valkonen-Korhonen^4
1Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland, ²Department of Applied Physics, University of Eastern Finland, Kuopio, Finland, ³Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland, ⁴Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland

Repetitive transcranial magnetic stimulation (rTMS) is able to induce long-term excitatory and inhibitory effects on cortical functions if applied repeatedly over several days. Thus, rTMS possesses a great potential in therapeutic applications and several promising therapies have already been developed. Whether rTMS causes structural neuroplasticity, however, remains mainly unknown. In this study, we found that bifrontal rTMS applied to dorsolateral prefrontal cortex (DLPFC) elicited structural changes in major depressive disorder patients. The increase in grey matter was found in the right post- and precentral gyri, which are both functionally connected to DLPFC.

Scott Quadrelli^1,2, Gerald Holtmann³, Nicholas Talley², Saadallah Ramadan², and Carolyn Mountford^4
1Queensland University of Technology, Brisbane, Australia, ²The University of Newcastle, Newcastle, Australia, ³The University of Queensland, Brisbane, Australia, ⁴Translational Research Institute, Brisbane, Australia

IBS is a characterised intermittent chronic abdominal pain and altered bowel habit in the absence of an organic cause.  Neurochemical changes may play a role in the pathophysiology of IBS.

Our pilot studies indicate that in vivo neuro 2D L-COSY monitors alterations to neurochemical pathways associated with IBS.

Christian Paret¹, Matthias Ruf¹, Traute demirakca¹, Christian Schmahl², and Gabriele Ende^1
1Neuroimaging, Central Institute of Mental Health, Mannheim, Germany, ²Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

fMRI neurofeedback on emotion-related brain activation via a brain-computer interface can improve brain self-regulation. We could show that neurofeedback is associated with amygdala down-regulation and alterations in frontolimbic functional connectivity in healthy female participants and female patients with borderline personality disorder. Real-time fMRI neurofeedback may in future help patients with severe emotion dysregulation to improve control over emotion-related brain networks.

Yi-Shin Chang¹, Mathilde Gratiot¹, Julia Owen¹, Anne Brandes-Aitken¹, Shivani Desai¹, Susanna Hill¹, Anne Arnett¹, Julia Harris¹, Elysa Marco¹, and Pratik Mukherjee^1
1University of California in San Francisco, San Francisco, CA, United States

Sensory processing disorders (SPD) affect 5-16% of school-aged children, and can cause downstream deficits of intellectual and social development. In this study, we use diffusion tensor imaging to study a cohort of 41 children with SPD and 41 typically developing children ages 8-12. We confirm and generalize results from our prior pilot study indicating disrupted posterior white matter in SPD, and further demonstrate a relationship between direct measurements of tactile and non-linguistic auditory function and white matter microstructure -- not just in SPD, but also in typically developing children. 

Jenny Molet¹, Pamela M Maras¹, Eli Kinney-Lang^1,2, Fasial Rashid², Neil Harris³, Autumn Ivy¹, Ana Solodkin^1,4, Tallie Z Baram^1,5, and Andre Obenaus^2,5
1Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, United States, ²Pediatrics, Loma Linda University, Loma Linda, CA, United States, ³Neurosugery, University of California, Los Angeles, Los Angeles, CA, United States, ⁴Neurology, University of California, Irvine, Irvine, CA, United States, ⁵Pediatrics, University of California, Irvine, Irvine, CA, United States

The effects of early-life adversity observed in the brain anatomy of rodents might be instructive about the human condition. Chronic early life stress in a rodent model results in dendritic paring in the dorsal hippocampus. High resolution volumetric MRI found hippocampal volume loss and DTI measures of microstructure found increased fractional anisotropy. Structural MRI measures can be used to find microstructural abnormalities related to dendritic morphological abnormalities. Thus, MRI metrics could be subsequently tested clinically to monitor adolescents at risk for neuropsychiatric illness.

Arjun Sethi¹, Hugo Critchley¹, Neil A Harrison¹, and Mara Cercignani^1
1Brighton & Sussex Medical School, Brighton, United Kingdom

Attention Deficit Hyperactivity Disorder (ADHD) is robustly associated with striatal abnormalities in childhood, though results in adults have been less definitive. Whilst this may reflect maturational normalisation, studies in adults have also typically been smaller. To enhance sensitivity to such changes we employ VBM analysis to MT saturation maps in adult ADHD, which have been shown to enhance localisation and segmentation of subcortical structures. In comparing these results to VBM analysis performed with T1 images in the same subjects, we show that MT-VBM is sensitive to striatal morphometric alterations that are not detected using T1-VBM.

Ren-Horng Wang¹, Vincent Chin-Hung Chen², Dah-Cherng Yeh³, and Jun-Cheng Weng^1,4
1Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan, ³Department of Breast Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ⁴Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Recent advances in breast cancer treatment have improved the long-term survival rate in cancer patients. The success in primary breast cancer treatment marks the importance of the post-treatment care. Cancer-related trauma after chemotherapy have been widely reported by breast cancer survivors. Previous study showed the decreased gray matter volume one month after chemotherapy completion, especially in frontal regions which is known for cognitive function. Another study indicated that there is reduction in cerebellar regions and right thalamus after the chemotherapy. However, several studies focused on the change of brain volume, but did not mention about the change of brain shape. Thus, in the study we aim to find out the differences of both brain volume and shape between chemotherapy-treated breast cancer patients and healthy subjects based on voxel-based morphometry (VBM) and vertex-wise shape analysis, respectively.  In our results, reduced gray matter volume of right thalamus and white matter volume of cerebellum, and altered shape of left amygdala, bilateral thalamus, and bilateral hippocampus was found in the chemotherapy-treated breast cancer patients compared to normal controls. 

Do-Wan Lee^1,2, Seockhoon Chung³, Hyun Ju Yoo⁴, Su Jung Kim⁴, Chul-Woong Woo², Sang-Tae Kim², Kyungwon Kim⁵, Jeong-Kon Kim⁵, Jin Seong Lee⁵, Choong Gon Choi⁵, Woo Hyun Shim⁵, Dong-Hoon Lee¹, Yoonseok Choi², and Dong-Cheol Woo^2
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of, ³Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ⁴Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea, Republic of, ⁵Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of

The aim of this study was to quantitatively assess the differences on the cerebral metabolites and to identify factors determining the alterations of endogenous biomolecules on stress-induced sleep disturbance in rats using in vivo 1H-MRS and in vitro LC-MS/MS. The GABA, Gln concentrations, Gln/Glu, Gln/tCr, and GABA/Glu ratios were significantly higher in SSP rats than in CNTLs. The serotonin concentrations were significantly lower in SSP rats than in CNTLs. Our in vivo 1H MRS and in vitro LC-MS/MS results suggest that the various metabolites and endogenous biomolecule signals in hippocampal region are particularly sensitive and vulnerable to stress-induced sleep perturbation.

Xinyu Hu¹, William Pettersson-Yeo², Lizhou Chen¹, Xi Yang³, Yanchun Yang ³, Qiyong Gong¹, and Xiaoqi Huang^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United Kingdom, ³Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of

Neuroimaging techniques hold the promise that they may one day aid the clinical assessment of individual psychiatric patients. However, the vast majority of studies published so far have been based on average differences between groups. The current study aimed to apply a novel multivariate pattern analysis technique known as relevance vector regression to evaluating the potential of resting-state functional magnetic resonance imaging for making accurate predictions about symptom progression in a relatively large sample of drug-naive patients with obsessive-compulsive disorder.

Arjun Sethi¹, Valerie Voon², Hugo Critchley¹, Neil A Harrison¹, and Mara Cercignani^1
1Brighton & Sussex Medical School, Brighton, United Kingdom, ²Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

The substantia nigra/ventral tegmental area (SN/VTA) is central to the modulation of dopaminergic networks implicated in Attention Deficit Hyperactivity Disorder (ADHD). However, little is known of its specific contribution to the disorder. Whilst motivational abnormalities and impulsivity are known to be related to the structure, it is not clear whether SN/VTA subcomponents differentially contribute to these deficits. Using diffusion MRI tractography parcellation of the SN/VTA, we show that increased waiting impulsivity in ADHD is related to the microstructure of the mesolimbic SN/VTA, whilst trait motivation is related to the nigrostriatal component. Unlike previous reports in unmedicated ADHD, we detect no motivational abnormalities in this medicated cohort. However, we report that patients who have been medicated longer show alterations in microstructure consonant with increased motivation.

Claudia Falfan-Melgoza¹, Anne Stephanie Mallien², Lei Zheng^1,3, Alexander Sartorius^1,2, Christoph Kellendonk ⁴, Peter Gass², and Wolfgang Weber-Fahr^1
1RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, ²Department of Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, ³Department of Radiation Oncology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany,⁴Department of Pharmacology, Columbia University, New York, NY, United States

Striatal D2R overexpression has been linked to the pathophysiology of schizophrenia. We used longitudinal voxel based morphometry on a transgenic mouse model before and after switching off the striatal D2R overexpression using doxycycline. Longitudinal registration showed a significant volume gain after the treatment in large areas covering frontal, prefrontal, striatal and temporal regions in the animals with D2R overexpression. The areas with volume increase over time show a remarkable plasticity as a result of the D2R downregulation within three weeks and correspond largely to regions with decreased gray matter volume commonly found in VBM studies on schizophrenia patients.

Youjin Zhao¹, Huaiqiang Sun¹, Su Lui¹, and Qiyong Gong^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of

The present study aimed to use surface-based morphometric analysis to characterize the alteration of cortical thickness in first-episode never-medicated adult MDD patients. 37 MDD patients and 41 healthy controls were enrolled. Results showed increased cortical thickness (p<0.05, False Discovery Rate) in left anterior and posterior cingulate cortex extending to medial superior frontal cortex, bilateral precentral cortex, left paracentral cortex, bilateral superior parietal cortex, left temporal poles, and right lateral occipital cortex in MDD patients than HC group. The data provide evidence that even early in the course of depression brain regions involved in mood regulation show cortical thickness abnormalities.

Gwang-Won Kim¹, Chung-Man Moon¹, Tae-Hoon Kim¹, and Gwang-Woo Jeong^1,2
1Research Institute of Medical Imaging, Chonnam National University Medical School, Gwang-ju, Korea, Republic of, ²Department of Radiology, Chonnam National University Medical School, Gwang-ju, Korea, Republic of

Obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD) are associated with abnormalities in the processing and regulation of anxiety. The purpose of this study was to evaluate gray matter (GM) and white matter (WM) volume alterations over whole-brain structures in healthy controls vs. patients with OCD vs. GAD using voxel-based morphometry (VBM), and further to assess the correlations of the GM and WM volume variations with the scores for anxiety severity in OCD and GAD.

Andreas Stadlbauer¹, Max Zimmermann¹, Karl Rössler¹, Stefan Oberndorfer², Michael Buchfelder¹, and Gertraud Heinz^3
1Department of Neurosurgery, University of Erlangen, Erlangen, Germany, ²Department of Neurology, University Clinic of St. Pölten, St. Pölten, Austria, ³Department of Radiology, University Clinic of St. Pölten, St. Pölten, Austria

Early detection of recurrence is crucial in patient care, but differentiation of treatment related necrosis from recurrent neoplasm is often difficult with conventional MRI (cMRI). We evaluated the usefulness for glioma recurrence grade increase detection of a multiparametric MRI for combined exanimation of oxygen metabolism and microvessel architecture. Forty-one patients with suspected recurrent glioma and one patient under antiangiogenic therapy were examined using vascular architecture mapping (VAM) and multiparametric quantitative BOLD (mp-qBOLD). 57% of LGG-patients, 22% of glioma WHO°III, and 32% of glioblastoma patients which were diagnosed as unsuspicious showed changes in oxygen metabolism and microvasculature indicative for recurrence.

Pavithra Viswanath¹, Jose Izquierdo-Garcia¹, Chloe Najac¹, Larry Cai¹, Russell Pieper², and Sabrina M Ronen^1
1Radiology, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

In this study we used hyperpolarized ¹³C-MRS to investigate pyruvate to lactate flux in IDH1 mutant cells. We found reduced hyperpolarized [1-¹³C]-lactate production from hyperpolarized [1-¹³C]-pyruvate in IDH1 mutant cells compared to wild-type. While there was no difference in lactate dehydrogenase A activity or NAD⁺/NADH, IDH1 mutant cells and patient samples showed reduced expression of monocarboxylate transporters MCT1 and MCT4. Comparison of hyperpolarized [1-¹³C]-lactate production between IDH1 wild-type and mutant lysates confirmed that reduced MCT expression was responsible for reduced hyperpolarized [1-¹³C]-lactate production. Thus, our study indicates that reduced MCT expression is a metabolic feature of the IDH1 mutation. 

Wilburn E Reddick¹, John O Glass¹, Elizabeth C Duncan¹, Jung Won Hyun², Qing Ji¹, Yimei Li², and Amar Gajjar^3
1Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States, ²Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, United States, ³Oncology, St. Jude Children's Research Hospital, Memphis, TN, United States

Diffusion tensor imaging from 30 childhood medulloblastoma patients were analyzed to assess changes in structural connectivity of the central executive network (CEN) in response to cranial irradiation. Significant drops in fractional anisotropy and axial diffusivity (AX) were demonstrated in most of the CEN subnetworks after irradiation. Furthermore, patients receiving the highest CRT dose had significantly decreased AX in all subnetworks of the CEN. These findings suggest significant reduction in the microstructural integrity within the CEN immediately after CRT in this population and support the use of the CEN model for evaluating changes in cerebral white matter early in therapy.

Ziying Yin¹, Kevin J. Glaser¹, Armando Manduca², Jamie J. Van Gompel³, Arvin Arani¹, Joshua D. Hughes³, Anthony Romano⁴, Richard L. Ehman¹, and John Huston III^1
1Radiology, Mayo Clinic, Rochester, MN, United States, ²Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States, ³Neurosurgery, Mayo Clinic, Rochester, MN, United States,⁴Naval Research Laboratory, Washington, WA, United States

The preoperative assessment of the surgical cleavage plane at the tumor-brain interface in meningiomas is important for surgical planning. A recently developed slip interface imaging (SII) technique is uniquely capable of directly assessing the degree of tumor adherence at the tumor-brain interface. In this study, SII was applied to assess the surgical cleavage plane between the tumor and the underlying brain in meningiomas. The correlation between the SII results and the surgical plane of cleavage was statistically significant (p=0.0014). The presence of a complete slip interface suggests the tumor can be removed using a dissection plane outside the pia mater.

Christiaan Hendrik Bas van Niftrik¹, Marco Piccirelli², Jan-Karl Burkhardt¹, Athina Pangalu², Antonio Valavanis², Michael Weller³, Oliver Bozinov¹, Luca Regli¹, and Jorn Fierstra^1
1Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland, ²Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland, ³Department of Neurology, University Hospital Zurich, Zurich, Switzerland

Neurovascular uncoupling (false negative BOLD activation) can be found in patients with high grade gliomas. An underlying mechanism could be impaired cerebrovascular reactivity. We determined overall cerebrovascular reactivity (CVR) as well as the perifocal CVR and used a healthy control group. We applied an automated tumor masking with determination of CVR in 7 consecutive rings of 3 mm.  We found an overall impaired CVR as well as significantly impaired intratumoral CVR and perifocal up to 12 mm. No such trend was found on the contralateral hemisphere, after flipping of the tumor mask.

Muge Karaman¹, Ying Xiong^1,2, He Wang³, Frederick C Damen^1,4, Yuhua Li⁵, and X. Joe Zhou^1,6
1Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States, ²Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, People's Republic of, ³Philips Research China, Shanghai, China, People's Republic of, ⁴Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States, ⁵Department of Radiology, Xinhua Hospital, Shanghai, China, People's Republic of, ⁶Departments of Radiology, Neurosurgery, and Bioengineering, University of Illinois at Chicago, Chicago, IL, United States

It has been well-recognized that the complexity of biological tissues, particularly the brain tumors with high degree of structural heterogeneity, requires more sophisticated diffusion models than a simple mono-exponential model due to the non-Gaussian behavior. Among these, a newly introduced model to MRI, the fractional motion (FM) model has been the focus of many biophysical studies at the molecular level. While the FM model has been demonstrated at the voxel-level, it has not been utilized to address a clinical question. In this study, we investigate the utility of FM model for differentiating low-grade and high-grade pediatric brain tumors.

Evan Neill¹, Manisha Dayal¹, Joanna Phillips², Llewellyn Jalbert¹, Soonme Cha¹, Annette Molinaro², Susan Chang², and Sarah Nelson^1
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States

Patients with recurrent low-grade Astrocytomas may experience a large variety of clinical disease courses and outcomes. Diffusion MR imaging and its associations with patient and tumor level characteristics provide an opportunity to use images as maps of tumor aggression and therefore prognosis. This study examines the relationships between the Apparent Diffusion Coefficient (ADC), histology and progress free survival in order to develop a colormap that highlights regions of the tumor with more aggressive characteristics. The colormaps provide an easier way for neuro-oncologists and neurosurgeons to interpret ADC images that can aid them in making decisions about how to manage their patients.

Gaurav Verma¹, Suyash Mohan¹, Sanjeev Chawla¹, Sumei Wang¹, Andrew Maudsley², Ronald Wolf¹, Steven Brem³, Robert Lustig⁴, Arati Desai⁵, and Harish Poptani^6
1Department of Neuroradiology, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Radiology, University of Miami, Miami, FL, United States, ³Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁴Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States, ⁵Department of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, United States, ⁶Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom

Differentiating brain tumor recurrence (True Progression, TP) from treatment effect (pseudoprogression, PsP) among enhancing neoplasms following radiation therapy by non-inavsive imaging may directly inform treatment strategies, yet similar imaging patterns  makes this difficult leading to  invasive biopsy or repeat surgery. Three-dimensional echo-planar spectroscopic imaging (EPSI) facilitates region-of-interest analysis with high-resolution metabolic data. In this study, we compared seven patients with PsP and seven with recurrent tumor using EPSI. Higher choline was detected from the contrast-enhancing, peritumoral and distal peritumoral regions in TP patients compared to PsP.

Lawrence Kenning¹, Martin D Pickles², Martin Lowry³, Chris Roland Hill⁴, Shailendra Achawal⁴, and Chittoor Rajaraman^4
1Centre for MR Investigations, Hull York Medical School, Hull, United Kingdom, ²Centre for MR Investigations, Hull York Medical School at University of Hull, Hull, United Kingdom, ³Hull York Medical School at University of Hull, Hull, United Kingdom, ⁴Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom

This study aimed to compare Intravoxel Incoherent Motion (IVIM) to more established measures of perfusion; Arterial Spin Labelling (ASL), Dynamic Contrast Enhanced (DCE) and Dynamic Contrast Susceptibility (DSC) imaging, both in tumours and white matter. Mean and 95th percentile values for f, D*, fD*, CBF, K^trans, v_e, v_b, rCBV and K₂ were calculated. Multiple correlations were observed. Significant correlations of note include CBF vs. fD*, v_b vs. rCBV and K^trans vs. K₂. Spatial registration of the 4 different methods yielded acceptable agreement given technical differences.

Eike Steidl^1,2,3, Oliver Baehr^2,3, Joachim P. Steinbach^2,3, Michael W. Ronellenfitsch^2,3, Friedhelm Zanella¹, Elke Hattingen¹, and Ulrich Pilatus^1
1Institute of Neuroradiology, Frankfurt am Main, Germany, ²Dr. Senckenberg Institute of Neurooncology, Frankfurt am Main, Germany, ³German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

Myoinositol is an organic osmolyte, with intracellular concentration changes depending on the extracellular osmolality. Since Bevacizumab reduces tumor edema, we asked whether the Myoinositol concentration changes during therapy.

We used ¹H-MRS to measure the Myoinositol concentrations in the tumor and contralateral control of patients with recurrent glioblastomas treated with Bevacizumab (n=30) and CCNU/VM26 (n=9).

Pre-therapeutic Myoinositol concentrations in the contralateral control were predictive of overall survival in patients treated with Bevacizumab. Furthermore our data confirm that recurrent glioblastoma show a strong metabolic reaction to Bevacizumab and support the hypothesis that Myoinositol might be a marker for early tumor cell invasion.

Prasanna Parvathaneni¹, Qiuting Wen², Joanna J Phillips ^3,4, Soonmee Cha^1,4, Susan M Chang⁴, Sarah J Nelson^1,5, and Janine M Lupo^1
1Department of Radiology and Biomedical Imaging, University of California San Francisco (UCSF), San Fransisco, CA, United States, ²Indiana University, Indianapolis, IN, United States, ³Department of Pathology, University of California San Francisco (UCSF), San Fransisco, CA, United States, ⁴Department of Neurological Surgery, University of California San Francisco (UCSF), San Fransisco, CA, United States, ⁵Department of Bioengineering and Therapeutic Sciences, University of California San Francisco (UCSF), San Fransisco, CA, United States

New non-Gaussian measurement techniques like neurite orientation dispersion and density imaging (NODDI) that allow quantification of specific tissue microstructure features can provide meaningful biophysical indices to overcome the low specificity of DTI. In this study we applied three compartment model based NODDI and DTI to histopathology and explored the correlation with tumor cellularity between non-enhancing and contrast enhancing lesions. Unlike in normal brain where V_in represents the neurite density, it was positively correlated with tumor grade and tumor score in tissue samples from the tumor region, indicating the association of V_in with tumor cellularity. Although NODDI is not directly built on tumor, it brings parameters that were sensitive to tumor cellularity, which may complement the conventional DTI model and adds specificity. Thus NODDI, when combined with DTI, could add value in understanding the heterogeneity of tissue microstructure in brain tumors.

Silun Wang¹, Jianming Ni², Liya Wang¹, Tricia King³, and Hui Mao^1
1Department of Radiology and Imaging Sciences, EMORY UNIVERSITY, ATLANTA, GA, United States, ²Medical Imaging Center, The Second Hospital of Wuxi, WuXi, China, People's Republic of,³Department of Psychology & Neuroscience Institute, Georgia State University, Atlanta, GA, United States

White matter injury is considered as a major contributory factor of treatment-induced neurotoxicity prevalent among childhood cancer survivors. DTI study with TBSS analysis shows significantly lower FA, λ_// and higher λ_⊥ in survivors compared to controls. DTI indices show unmatched white matter regions with significant difference.  In comparison of FA, λ_// may be more sensitive to detect white matter injury.  Combining analysis of DTI indices provide additional information to explore white matter injury induced by radiotherapy or chemotherapy. 

Francesca Branzoli^1,2, Anna Luisa Di Stefano^2,3,4, Malgorzata Marjanska⁵, Romain Valabregue^1,2, Stephane Lehericy^1,2, and Marc Sanson^2,3
1Brain and Spine Institute (ICM), Center for Neuroimaging Research (CENIR), F-75013, Paris, France, ²INSERM U1127/CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 06, ICM, F-75013, Paris, France, ³AP-HP, GH Pitié-Salpêtrière, Service de Neurologie 2, F-75013, Paris, France, ⁴Division of Neurology, Foch Hospital, Paris, France, ⁵Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, United States

Reliable quantification by magnetic resonance spectroscopy of the oncometabolite 2-hydroxyglutarate (2HG) has important implications in diagnosis of IDH mutation, prognosis, as well as assessment of the efficacy of anti-IDH targeted therapies. In this study, we employed two approaches for 2HG detection previously described, e.g., difference spectroscopy and optimized for 2HG detection conventional spectroscopy, in order to assess for the first time the specificity and sensitivity of the two methods, and to relate these results to the natural history and the neuroradiological status of patients with glioma.  

Michael Breckwoldt¹, Julia Bode², Felix Kurz¹, Angelika Hoffmann¹, Martin Ott², Katrin Deumelandt², Gergely Solecki², Sara Chiblak², Amir Abdollahi², Frank Winkler², Michael Platten², Sabine Heiland¹, Martin Bendszus¹, and Björn Tews^2
1Neuroradiology, University of Heidelberg, Heidelberg, Germany, ²German Cancer Research Center, Heidelberg, Germany

Gliomas are malignant brain tumors that depend on neoangiogenesis. Novel imaging methods are required to assess vascularization status, treatment effects and disease progression. We developed a combined MR and optical vascularization “tool kit” to study neoangiogenesis in mouse glioma models. We use T2* post contrast imaging (iron oxide nanoparticle or Gd-based) of vascular susceptibility signals and innovative ultramicroscopy (UM) of cleared brains. T2* imaging identifies single arterioles and venules in glioma development. Correlated UM of fluorescently labeled microvessels shows typical features of pathological vessels (increased caliber, density and tortuousness). Thus, MR-UM facilitates the preclinical search for more effective antiangiogenic agents.

Yufen Chen¹ and Todd B Parrish^1
1Radiology, Northwestern University, Chicago, IL, United States

In clinical settings, dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) data are rarely acquired together as both require a full single dose for optimal contrast-to-noise-ratio (CNR). However, both techniques offer complementary information that aid in the assessment of tumors. Current double acquisition methods acquire the DCE scan first with a half dose to minimize leakage effects in the subsequent DSC scan, compromising both scans. Here, we demonstrate the feasibility of an automatically switching DSC-DCE scan sequence by monitoring the signal intensity of the DSC scan, allowing acquisition of both datasets with a single contrast dose.

Peter de Blank^1,2, Dan Ma², Chaitra Badve², Shivani Pahwa², Sara Dastmalchian³, Duncan Stearns^1,2, Deborah Rukin Gold^2,4, Krystal Tomei^2,5, Jill S Barnholtz-Sloan², Andrew Sloan^2,5, Vikas Gulani^2,6, and Mark Griswold^2
1Pediatrics, University Hospitals, Cleveland, OH, United States, ²Case Western Reserve University, Cleveland, OH, United States, ³University Hospitals, Cleveland, OH, United States, ⁴Neurology, University Hospitals, Cleveland, OH, United States, ⁵Surgery, University Hospitals, Cleveland, OH, United States, ⁶Radiology, University Hospitals, Cleveland, OH, United States

This study uses magnetic resonance fingerprinting to investigate relaxometry values in pediatric and young adult primary brain tumors.  Six children with primary brain tumors were scanned:  3 with low-grade tumors and 3 with high-grade tumors.  T1 and T2 values of tumor were significantly different from contralateral white matter.  T1, T2 quantification of tumor were also significantly different between high- and low-grade tumors.  Three subjects underwent serial observations: 2 received therapy and 1 did not.  Subjects that underwent surgical decompression and chemotherapy appeared to have larger changes in T1 values than those that were only observed.

Qing Ji¹, John O. Glass¹, Elizabeth C. Duncan¹, Amar Gajjar², and Willburn E. Reddick^1
1Diagnostic Imaging, St.Jude Children's Research Hospital, Memphis, TN, United States, ²Oncology, St.Jude Children's Research Hospital, Memphis, TN, United States

Global and regional cerebral white matter changes induced by cranial radiotherapy (CRT) were analyzed by comparing Pre-CRT and Post-CRT diffusion tensor imaging (DTI) from 30 childhood medulloblastoma patients using a structural connectivity network model and graph theory approaches. At the global level, global network efficiency and character path were significantly changed for the whole network. At the regional level, 17 of 82 network nodes had significantly decreased local efficiencies, and 14 of those nodes also had significantly decreased clustering coefficients. These findings suggest significant reduction in the microstructural integrity immediately after CRT in this population.

Christine Preibisch^1,2, Mathias Lukas³, Anne Kathrin Kluge¹, Claus Zimmer¹, Stefan Förster^3,4, and Thomas Pyka^3
1Dept. of Neuroradiology, Technische Universität München, Munich, Germany, ²Clinic for Neurology, Technische Universität München, Munich, Germany, ³Clinic for Nuclear Medicine, Technische Universität München, Munich, Germany, ⁴Clinic for Nuclear Medicine, Klinikum Bayreuth, Bayreuth, Germany

Hypoxia plays an important role in prognosis and therapy response of cancer. This study explores the characteristics of multi-parametric measurements of relative oxygen extraction fraction (rOEF) in a sample of 36 mostly high grade glioma patients. This study confirms previous results in human glioma where rOEF values were found to increase with tumor grade but does not find a similar increase of a supposedly hypoxic tumor area with tumor grade. According to present results, high rOEF values, supposedly corresponding to a high oxygen extraction, prevail in edematous tissue with low rCBV. Whether this translates into tissue hypoxia, needs further investigation.

Liya Wang^1,2, Hongbo Chen^1,3, Tricia Z King⁴, and Hui Mao^1
1Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, ²Radiology, Cancer Hospital Chinese Academy of Medical Sciences at Shenzhen, Shenzhen, China, People's Republic of, ³School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, China, People's Republic of, ⁴Psychology and Neuroscience Institute, Georgia State University, Atlanta, GA, United States

Pediatric brain tumors and associated treatment affect brain development and functional network. We investigated the functional connectivity (FC) of adult survivors of pediatric brain tumors using resting-state functional MRI and independent component analysis to better understand the neural mechanisms underlying long term cognitive outcomes of the survivors. It was found that survivors exhibited differences in the FC in executive control network, default mode network and salience network compared to demographically-matched controls with increased number of effective functional connectivities and increased FC strength in survivors compared the controls.

Kazuhiro Murayama¹, Takahiro Ueda¹, Takashi Fukuba², Shigeharu Ohyu³, Ayako Ninomiya³, Masato Ikedo³, Kazuhiro Katada⁴, and Hiroshi Toyama^1
1Radiology, Fujita Health University, Toyoake, Japan, ²Radiology, Fujita Health University Hospital, Toyoake, Japan, ³Toshiba Medical Systems, Otawara, Japan, ⁴Joint Research Laboratory of Advanced Medical Imaging, Fujita Health University, Toyoake, Japan

A combination of Ktrans, Ve, and rCBV would be useful in differentiating between central nervous system lymphoma and gliomas. Dynamic contrast-enhanced MRI parameters have been successfully applied to obtain quantitative estimates of the permeability of brain tumors for characterization of the vascular microenvironment.

Rifeng Jiang¹, Jingjing Jiang¹, Jingjing Shi¹, Yihao Yao¹, Nanxi Shen¹, Changliang Su¹, Ju Zhang¹, and Wenzhen Zhu^1
1Radiology, Tongji Hospital, Wuhan, China, People's Republic of

Compared with conventional diffusion metrics, the kurtosis metrics derived from DKI in the solid region of the tumors were better diagnostic factors in distinguishing HGGs from LGGs and identifying grade II, III and IV gliomas. The kurtosis metrics offered great potential to noninvasively predict the cellular proliferation of gliomas. DKI was also useful to evaluate the survival of glioma patients, and MK was a significant death risk in glioma patients.

Andrea Horváth^1,2,3, Csanád Várallyay¹, Daniel Schwartz¹, Prakash Ambady¹, Péter Bogner⁴, and Edward Neuwelt^1
1Department of Neurology, Oregon Health and Science University, Portland, OR, United States, ²Department of Neurosurgery, University of Pécs, Pécs, Hungary, ³Diagnsotic Center of Pécs, Pécs, Hungary,⁴Department of Radiology, University of Pécs, Pécs, Hungary

Ferumoxytol is an alternative, investigational, iron-based MRI contrast agent, which might be beneficial in the accurate diagnosis of treated glioma patients. In this study we investigated how gadolinium and 24 hour ferumoxytol enhancement change as a result of Avastin treatment. The enhancement volumes and normalized signal intensities before and after Avastin treatment were calculated with histogram analysis and were compared between contrast agents. Changes in enhancement volumes and in signal intensities in response to Avastin were not different between contrast agents. Ferumoxytol shows good potential in brain tumor imaging.

Aram Tonoyan¹, Ezequiel Farrher², Ivan Maximov³, Farida Grinberg^4,5, Elena Lyubimova⁶, Ludmila Fadeeva¹, Eduard Pogosbekyan¹, Nadim Joni Shah^2,5, and Igor Pronin^1
1Neuroimaging, Burdenko Neurosurgery Institute, Moscow, Russian Federation, ²Institute of Neuroscience and Medicine – 4, Medical Imaging Physics, Forschungszentrum Juelich GmbH, Juelich, Germany, ³Experimental physics III, TU Dortmund University, Dortmund, Germany, ⁴Institute of Neuroscience and Medicine – 4, Medical Imaging Physics, Forschungszentrum Juelich GmbH, Julich, Germany, ⁵Faculty of Medicine, Department of Neurology, RWTH Aachen University, JARA, Aachen, Germany, ⁶Radiology, Krasnodar Regional Hospital, Krasnodar, Russian Federation

MRI allows one to detect and visualize the primary and metastatic tumours in the brain. However, conventional methods suffer from a poor contrast. In turn, it leads to a problem in proper diagnostics of the tumour origins. In the present work we demonstrated the potential of kurtosis imaging technique in the tumour differentiation of primary tumour and metastasis cancers.

Vera Catharina Keil¹, Kanishka Hiththetiya², Gerrit H. Gielen³, Matthias Simon⁴, Bogdan Pintea⁴, Anna Vogelgesang¹, Juergen Gieseke^1,5, Burkhard Maedler⁵, Hans Heinz Schild¹, and Dariusch Reza Hadizadeh^1
1Department of Radiology, Universitätsklinikum Bonn, Bonn, Germany, ²Center for Pathology, Universitätsklinikum Bonn, Bonn, Germany, ³Department of Neuropathology, Universitätsklinikum Bonn, Bonn, Germany, ⁴Clinic for Neurosurgery and Stereotaxy, Universitätsklinikum Bonn, Bonn, Germany, ⁵Philips Healthcare, Best, Netherlands

Tissue perfusion is co-defined by anatomical factors of the microvasculature. If and how kinetic parameters of T1w dynamic-contrast enhanced (T1-DCE) MRI fit into this anatomical perfusion model, is a topic of on-going discussion. Based on the extended Tofts model (ETK) we therefore performed a focal analysis of kinetic parameters in meningioma and surgically retrieved precisely corresponding tissue specimens. Their microvasculature underwent multimodal computerized analysis. Kinetic parameters were found to correlate poorly and inconsistently with the microvascular anatomy on both an inter- and intra-individual level.