Tsuyoshi Matsuda¹, Hirohiko Kimura², Masayuki Kanamoto³, and Hiroyuki Kabasawa^1
1MR Applications and Workflow, GE Healthcare Japan Corporation, Tokyo, Japan, ²Department of Radiology, University of Fukui, Fukui, Japan, ³Radiological Center, University of Fukui Hospital, Fukui, Japan

DANTE preparation pulse for the arterial spin-labeling (ASL) sequence was developed to reduce the intravascular signal based on the hypothesis that DANTE could enable sufficient vascular signal suppression without any technical drawback. Phantom and human volunteer experiments were performed to evaluate the proposed method. A similar level of vascular suppression effect was observed with both MSDE and DANTE-prepared ASL sequence from phantom experiment. A signal intensity uniformity of vascular suppressed perfusion weighted images was superior with DANTE compared to MSDE. These results indicated that DANTE-preparation could be used as a vessel signal suppression method for ASL.

Michael Wyss¹, Laetitia Vionnet¹, Mike Bruegger^1,2, Bernd Daeubler³, Lars Kasper^1,4, Daniel Nanz⁵, Marco Piccirelli³, David O. Brunner¹, and Klaas P. Pruessmann^1
1Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland, ²Center of Dental Medicine, University of Zurich, Zurich, Switzerland, ³Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland, ⁴Translational Neuromodeling Unit, Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland, ⁵Institute of Diagnostic and Interventional Radiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland

The human brainstem anatomy is challenging to image in vivo on a single subject basis. The densely-packed interspersion of nuclei and white matter tracts cannot typically be imaged with an image contrast strong enough for differentiation of relevant substructures. We present an MR imaging approach at 7 Tesla that requires two high resolution MR acquisitions. From the two data sets, four image series with varying contrast weightings can be derived and used to delineate brainstem anatomy. The proposed strategy resulted in exceptionally high image quality enabling differentiation of several brainstem substructures that are hardly discernible in commonly acquired MR images. 

Andre Obenaus^1,2, Eli Kinney-Lang^1,3, Duke Shereen⁴, Ana Solodkin^3,4, and Tallie Z Baram^2,3
1Pediatrics, Loma Linda University, Loma Linda, CA, United States, ²Pediatrics, University of California, Irvine, Irvine, CA, United States, ³Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, United States, ⁴Neurology, University of California, Irvine, Irvine, CA, United States

The amygdaloid complex, including the basolateral nucleus (BLA) are critically important in mediating emotional and adaptive responses to stress.  However, lack of contrast between the BLA and the surrounding gray matter (GM) has hampered routine imaging. We report a novel DTI paradigm to identify the BLA in the rodent brain. We derived BLA volumes and confirmed these with histological measures. Our approach can be used to study the morphological and functional consequences of emerging neuropsychiatric diseases, both in experimental and clinical studies.

Isaac Huen¹, Joanne Beckmann¹, Yuriko Suzuki², Maria A Zuluaga³, Andrew Melbourne³, Matthias JP van Osch⁴, David Atkinson⁵, Sebastien Ourselin³, Neil Marlow¹, and Xavier Golay^1
1Institute of Neurology, University College London, London, United Kingdom, ²Philips Medical Systems, Philips, Tokyo, Japan, ³Centre for Medical Image Computing, University College London, London, United Kingdom, ⁴C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Netherlands, ⁵Centre for Medical Imaging, University College London, London, United Kingdom

The properties of the cerebral vasculature are of clinical relevance and thus of interest for investigation. Here an ASL-based 3D angiographic technique (CINEMA-STAR) is used to measure blood arrival times and blood velocities of a bolus labeled in the neck. Results are shown to be in broad agreement with existing methods.

Riccardo Metere¹, Markus Morawski², Carsten Jäger², and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany

The tissue composition of the brain can be related to different contrast sources in quantitative MRI. Particularly, myelin and iron are considered to be major sources of MRI contrast, with strong correlation to $$$T_1$$$ and $$$T_2^*$$$, respectively. However, other components, may also play a role in contrast generation. In this work, we present experiments in post-mortem human brain specimens to disentangle the potential contribution of the hyaluronan-based extracellular matrix from other contrast sources in quantitative relaxation maps. This was achieved by comparing images of digested and undigested samples that were otherwise subject to the same environmental conditions.  

Denis Peruzzo¹, Umberto Castellani², Fabio Triulzi^1,3, Andrea Righini⁴, Cecilia Parazzini⁴, and Filippo Arrigoni^1
1Neuroimaging Unit, Scientific Institute IRCCS “Eugenio Medea”, Bosisio Parini, Italy, ²Department of Computer Science, University of Verona, Verona, Italy, ³Department of Neuroradiolody, Fondazione IRCCS “Ca’ Granda” Ospedale Maggiore Policlinico, Milano, Italy, ⁴Department of Pediatric Radiology and Neuroradiology, Children Hospital “Vittorio Buzzi”, Milano, Italy

The diagnosis of brain malformations is usually based on the visual inspection of MRI images by trained neuroradiologists. The resulting procedure is therefore subjective and mainly provides a qualitative description of the detected malformations. In this study, we propose an assisted diagnosis tool (ADT) for the analysis of the corpus callosum from structural T1-weighted images. The method detects and characterizes different kind of malformations (local/diffuse, homogeneous/heterogeneous). Inter-subject reproducibility experiments showed that the agreement rate significantly improved from 67.5% to 79.3% using the proposed method.

Jolanda M Spijkerman¹, Esben T Petersen², Peter R Luijten¹, Jeroen Hendrikse¹, and Jaco J M Zwanenburg^1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Centre for Functional and Diagnostic Imaging and Research, Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark

The relaxation parameters of CSF may have potential as imaging markers in several diseases. In this work T₂ mapping of CSF in the lateral ventricles and in the fourth ventricle was performed in six volunteers at 7T, with comparison to 3T. The sensitivity for B₁ was assessed by comparing the T₂s in both regions, with equal B₁ at 3T and different B₁ at 7T. T₂ values were significantly lower at 7T compared to 3T. No significant difference was found between the lateral and the fourth ventricular T₂s at 7T (and 3T), indicating negligible B₁-sensitivity for the used T₂-mapping sequences.

Yuan Liu^1,2, Benjamin Odry², Hasan Ertan Cetingul², and Mariappan Nadar^2
1Vanderbilt Institute in Surgery and Engineering, Vanderbilt University, Nashville, TN, United States, ²Medical Imaging Technologies, Siemens Healthcare, Princeton, NJ, United States

Automatic brain extraction, as a standard pre-processing step, typically suffers from a long runtime and inaccuracies caused by brain variations and limited qualities of MR images. We propose a generic supervised learning framework that builds binary classifiers to identify brain and non-brain tissues at different resolution levels, hierarchically performs voxel-wise classifications for a test subject, and refines the brain boundary using narrow-band level set technique on the classification map. The proposed method is evaluated on multiple datasets with different acquisition sequences and scanner types using uni- or multi-contrast images and shown to be fast, accurate, and robust.

Neville D Gai¹, Yi Yu Chou^1,2, Dzung Pham^1,2, and John A Butman^1
1Radiology & Imaging Sciences, NIH, Bethesda, MD, United States, ²Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United States

Arterial spin labeling is typically performed with segmented k-space acquisition schemes to reduce B0 inhomogeneity related distortion. Non-segmented techniques offer the advantage of higher SNR/time allowing  greater brain coverage in shorter scan times. Here we use a modified 3D EPI acquisition scheme along with pseudo-continuous arterial spin labeling to correct for B0 inhomogeneity related distortion. By employing phase encoding along opposite directions in alternating control-label pairs and with subsequent post-processing, we correct for the distortion. CBF images were compared with GM masks obtained from relatively distortion free MPRAGE images to show improved localization of the CBF maps. 

Se-Hong Oh¹, Ken Sakaie¹, Stephen E. Jones¹, and Mark J. Lowe^1
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States

Accurate identification of the thalamus sub-structures is therefore important for localization of specific nuclei and for the understanding of brain function. However, sub-structures of the thalamus are so small and have intermediate signal characteristics between grey/white matter it has been difficult to identify them with conventional MR imaging technique. In this work, in-vivo T₁ value at 7T are measured using fast T₁ mapping technique in less than 2 min and optimized inversion time to generate optimal contrast from the thalamus. The optimized results reveal markedly improved anatomical detail of the sub-structures of the thalamus, including their detailed locations.

Xiaodong Zhong¹, Tucker Lancaster², Zihan Ye³, Deqiang Qiu², Brian M. Dale⁴, John N. Oshinski^2,3, and Amit Saindane^2
1MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States, ²Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, ³Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States, ⁴MR R&D Collaborations, Siemens Healthcare, Cary, NC, United States

In this work, we demonstrated that the DENSE technique can be used to measure and group motion of different brain regions. Preliminary results in 9 volunteers showed that the brain regions near the CSF (midbrain, pons, medulla and optic chiasm) had larger motion magnitude than regions far away (frontal lobe, occipital lobe, parietal lobe and cerebellum). DENSE enables us to investigate brain motion to a level of detail that has not been previously possible. The findings in this study may bring new insight into brain motion and provide useful information to improve potential imaging and therapy techniques.

Lee Bremner Reid¹, Martin V Sale², Ross Cunnington^2,3, and Stephen E Rose^1
1e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, Australia, ²Queensland Brain Institute, The University of Queensland, Brisbane, Australia, ³School of Psychology, The University of Queensland, Brisbane, Australia

Detecting neuroplasticity requires highly sensitive measurements that may be outside the bounds of standard parcellation-seeded tractography. Earlier attempts to measure neuroplasticity induced by motor learning have utilised voxelwise analyses. Such analyses are reliant on precise registration, can have low statistical power, and provide little certainty as to the functional relevance of areas of detected change. We have measured motor-learning-induced neuroplasticity along corticomotor and thalamocortical tracts using fMRI-seeded diffusion-MRI, finding that changes uniquely occur in the corticomotor tract. Unlike previous analyses, we reveal that these changes occur throughout the corticomotor tract, not just near the grey-/white-matter interface.

Patric Birr¹, Andreas Fehlner², Sebastian Hirsch², Florian Dittmann², Jing Guo², Jürgen Braun², Ingolf Sack², and Stefan Hetzer^3
1Physics, Humboldt University Berlin, Berlin, Germany, ²Radiology, Charité - University Medicine Berlin, Berlin, Germany, ³Berlin Center for Advanced Neuroimaging, Berlin, Germany

Two imaging modalities, magnetic resonance elastography (MRE) and arterial spin labeling (ASL), were used to compare mechanical properties of brain tissue with regional perfusion across subcortical brain regions. An inverse correlation of stiffness (|G*|) and average perfusion (CBF) was observed in deep gray matter when accounting for structurally and functionally distinct areas. In the |G*|-CBF space, globus pallidus, hippocampus, thalamus and amygdala clearly clustered from putamen and nucleus accumbens highlighting their anatomical differences in network density and vasculature. Differences in the microstructure between the striatum and other analyzed regions are not apparent by MRE or ASL alone.

Hyunseok Seo¹, Dongchan Kim¹, Jaejin Cho¹, Kinam kwon¹, Byungjai Kim¹, and HyunWook Park^1
1Electrical Engineering, KAIST, Daejeon, Korea, Republic of

The proposed method is based on the perfusion model of intravoxel incoherent motion (IVIM), which assumes that perfusion is a microcirculation of blood in the capillary network. The method introduces two-types of bi-polar gradients in a radial spin-echo sequence, a new ordering of bi-polar gradients for isotropic perfusion weighting, and signal models for quantitative analysis of perfusion. To verify the proposed method, in-vivo imaging in 3 T MRI was performed, and the proposed method offers the high-resolution quantitative perfusion map. 

Maria Luisa Mandelli¹, Matteo Paoletti², Nico Papinutto³, Bagrat Amirbekian^3,4, Roland G Henry^3,4,5, Eduardo Caverzasi^3,6, and Maria Luisa Gorno-Tempini^1
1Neurology, Memory Aging Center, UCSF, San Francisco, CA, United States, ²Radiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, ³Neurology, UCSF, San Francisco, CA, United States,⁴Bioengineering Graduate Group, Berkeley, CA, United States, ⁵Radiology and Biomedical Imaging, San Francisco, CA, United States, ⁶Brain and Behavioral Sciences, Pavia, Italy

The insula cortex is involved in different functions, however its cortical connections have not yet been extensively explored. Whole brain tractography with Q-ball residual bootstrap algorithm was performed in 17 controls. Insula and the cortex regions were used as ending-ROIs. We found structural connections between the insula and 22 cortical regions for each hemisphere. After registered the images to the MNI space, the parcellation of the insula was obtained based on the ending-tract connected with each of the cortex region. Availability of a template atlas of insular structural connectivity would contribute to a better understanding of its multiple functions.

Hengtong Li¹, Heather T Ma¹, Jingbo Ma¹, Chenfei Ye¹, and Shuai Mao^1
1Department of Electronic and Information Engineering, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, China, People's Republic of

This study proposed 4L and LV-based methods to improve the brain segmentation accuracy and eddiciency of multi-atlas brain segmentation. The atlas database contains T1 images of brain from 77 subjects. These two methods were adopted to calculate the Dice between the target image and each atlas. We compared the proposed methods with MI-based method and randomly selected method for geriatric, adult and pediatric populations. The segmentation accuracy was evaluated by Dice and the results show that the accuracy of 4L and LV-based methods has great improvement. In addition, the proposed pre-selection is more efficient.

Liliana E. Ma¹, Can Wu^1,2, Susanne Schnell¹, Christophe Chnafa³, David Steinman³, and Michael Markl^1,2
1Department of Radiology, Northwestern University, Chicago, IL, United States, ²Department of Biomedical Engineering, Northwestern University, Evanston, IL, United States, ³Department of Mechanical Engineering, University of Toronto, Toronto, ON, Canada

Characterization of cerebral arterial flow waveforms in healthy subjects can help establish a comparison baseline in studies of cerebrovascular disease and provide key inputs for computational fluid dynamic studies. The purpose of this study was to quantitatively characterize cerebral arterial waveforms in healthy adult subjects by extracting arterial pulsatility and flow waveforms along the ICA and MCA using 4D flow MRI. Our findings demonstrated no significant changes in arterial pulsatility from proximal ICA to distal MCA, although a decreasing trend was observed from the proximal to distal carotid siphon in young adults. 

Anzar Abbas¹, Waqas Majeed², Garth Thompson³, and Shella Keilholz^4
1Neuroscience Program, Emory University, Atlanta, GA, United States, ²School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan, ³Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ⁴Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States

Quasi-periodic patterns that include alternation between the default mode and task positive networks are known to occur in humans and their templates can be acquired using a previously developed QPP-finding algorithm. The algorithm, however, relies on a user-specified window length for the QPP, the optimal size of which is not known. We apply the QPP algorithm on rsfMRI scans using varying window lengths and compare properties of observed QPP templates. Our results indicate an optimal window length adequately depicting QPP occurrences in human functional data. This will allow us to accurately characterize QPPs and study how they may be affecting functional connectivity measurements and brain function.

Andrew Melbourne¹, Enrico De Vita^2,3, John Thornton^2,3, and Sebastien Ourselin^1
1Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ²Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, ³UCL Institute of Neurology, University College London, London, United Kingdom

This work combines information from acquisitions of diffusion-weighted and T2 relaxometry data to allow improvements in separating out multiple compartments. This is particularly useful when fitting a multi-compartment diffusion model or a multi-component T2 relaxometry model. Work of this type might allow improved fitting of multi-modal derived parameters such as the g-ratio.

Ferran Prados^1,2, Bhavana S Solanky², Patricia Alves Da Mota², Manuel Jorge Cardoso¹, Wallace J Brownlee², Frank Riemer³, David H Miller², Xavier Golay⁴, Sebastien Ourselin¹, and Claudia Angela Michela Gandini Wheeler-Kingshott^2,5
1Translational Imaging Group, Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ²NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, United Kingdom, ³Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ⁴Brain Repair & Rehabilitation, UCL Institute of Neurology, University College London, London, United Kingdom, ⁵Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy

Non-invasive measurement of in vivo total sodium concentration (TSC) has been possible due to advances in sodium MRI at clinical field strengths. Changes in white and grey matter concentrations have been reported in a number of different diseases like Multiple Sclerosis. However, the presence of regional differences in normal healthy brain TSC has not been yet investigated. Here we use Geodesic Information Flow technique for computing per subject brain parcellations to allow differentiation of these areas and subsequently characterization of  regional TSC in healthy controls. 

Ravi Prakash Reddy Nanga^1,2, Kosha Ruparel², Dina Appleby², Mark Elliott¹, Hari Hariharan¹, Ravinder Reddy¹, and Neill C Epperson^2,3,4,5
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, ³Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, ⁴Penn Center for the Study of Sex and Gender in Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, ⁵Penn Center for Women’s Behavioral Wellness, Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States

We explored the potential for sex differences in brain Gamma-aminobutyric acid (GABA), glutamate (Glut) and neural response to an acute dose of gabapentin by using proton magnetic resonance spectroscopy (¹H-MRS) followed by functional magnetic resonance imaging (fMRI) at 7T.

Jeroen C.W. Siero¹, Jeroen H.J. de Bresser¹, Lisa van der Kleij¹, Jill B. de Vis¹, and Jeroen Hendrikse^1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Here we investigate brain volume changes upon a vasodilatory hypercapnic stimulus as a potential alternative to obtain cerebral tissue reactivity information. Using relatively standard 3D T1-weighted scans (MP-RAGE) and segmentation software we show significant volume changes (in all subjects) in subcortical deep gray matter areas which were paralleled by decreases in ventricular volume. This approach (volume reactivity) could yield novel insights on cerebral tissue reactivity in healthy and disease and be a potential alternative in cases where BOLD or ASL CVR interpretation can be ambiguous.

Gabrielle Fournet^1,2, Luisa Ciobanu¹, Jing Rebecca Li², Alex Cerjanic³, Brad Sutton³, and Denis Le Bihan^1
1CEA Saclay/Neurospin, Gif-sur-Yvette, France, ²INRIA Saclay, Palaiseau, France, ³Beckman Institute of Advanced Science and Technology, Urbana, IL, United States

IntraVoxel Incoherent Motion (IVIM) imaging allows to extract perfusion parameters from a series of diffusion weighted images. We show that the standard mono-exponential model used to describe the IVIM signal can be improved by switching to a bi-exponential model. Multiple diffusion time rat brain images were acquired at 7T and compared to numerical simulations of blood flow through the microvascular network. Our results demonstrate that the bi-exponential model better describes the data especially at short diffusion times and suggest that the IVIM signal comprises the contributions from two different vascular pools: small vessels (capillaries) and medium sized-vessels.

ZHE HAN TOH¹, WENG HANG WONG¹, QING LONG GU¹, KAI-HSIANG CHUANG², KUAN-JIN LEE², JULIAN GAN³, and PHUA HWEE TANG^1
1Department of Diagnostic and Interventional Imaging, KK WOMEN'S AND CHILDREN'S HOSPITAL, SINGAPORE, Singapore, ²Singapore Bio-Imaging Consortium, A*STAR, SINGAPORE, Singapore,³Siemens Healthcare, Regional Headquarter, SINGAPORE, Singapore

We compared 3 versions of Arterial Spin Labelling (ASL) available ( single-TI 3D-PASL, multi-TI 3D-PASL and 2D-pCASL) on 3T Siemens MRI scanner Skyra  in 10 normal healthy adults with normal body mass index (BMI) at 3 different time points (baseline, 1 week later, 2 to 3 month later).  There was good replicability of all 3 ASL techniques (correlation coefficients range from 0.55 to 0.77). Values acquired with these ASL techniques agree with the published normal range of cerebral blood flow values in adults.  There is no significant difference in the CBF obtained with single-TI 3D-PASL, multi-TI 3D-PASL and 2D-pCASL.

Colm McGinnity¹, Radhouene Neji², Jane MacKewn¹, James Stirling¹, Sami Jeljeli¹, Titus Lanz³, Christian Geppert⁴, Mark Oehmigen⁵, Harald Quick⁵, Gary Cook¹, and Alexander Hammers^1
1King's College London, London, United Kingdom, ²Siemens Healthcare, Frimley, United Kingdom, ³Rapid Biomedical, Wuerzburg, Germany, ⁴Siemens Healthcare, Erlangen, Germany, ⁵University Duisburg-Essen, Essen, Germany

We investigate the feasibility of in-vivo simultaneous brain 18F FDG PET imaging and 13C MR spectroscopy using a dedicated dual-tuned 1H-13C coil with low PET attenuation. Simultaneous in-vivo 18F FDG PET imaging and 13C unlocalized natural abundance MR spectroscopy were performed on three patients. Initial results show the technical feasibility of the simultaneous in-vivo measurement with good spectral and PET image quality.

Marco Piccirelli¹, Christopher Bockisch², Marc Bovet³, and Roger Luechinger^4
1Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland, ²Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland, ³ICT, University Hospital Zurich, Zurich, Switzerland, ⁴Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

To improve neuro-ophthalmologic surgery, biomechanical inside about the pathophysiological dynamic of eye movements is needed. High spatiotemporal resolution dynamic MR imaging of the orbit during eye movement shall provide such information. To enable clinical use, the acquisition design needs to accommodate limited patient capabilities to perform repetitive eye movement accurately.

Yulin V Chang¹, Marta Vidorreta², Ze Wang³, and John A Detre^2
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Neurology, University of Pennsylvania, Philadelphia, PA, United States, ³Hangzhou Normal University, Hangzhou, Zhejiang, China, People's Republic of

3D coverage of the whole brain by using RARE-refocused stack-of-2D-spirals often suffers from low temporal/spatial resolution due to the long spiral readout or long echo train. In this work we present a method that allows whole-brain coverage at 3 mm isotropic spatial resolution with one- or two-segment, accelerated acquisitions in both partition and spiral directions. The technique was applied in conjunction with background-suppressed pCASL, resulting in improved temporal/spatial resolution for quantification of cerebral blood flow.

Michael N Hoff¹, Swati R Levendovszky¹, and Jalal B Andre^1
1Radiology, University of Washington, Seattle, WA, United States

Cerebral blood flow (CBF) may be quantified using pseudo-continuous arterial spin labeling (pCASL), but pCASL suffers from image distortion due to its long echo planar imaging (EPI) readout.  Phase labeling for additional coordinate encoding (PLACE) is employed here to remove distortion.  EPI images and pCASL subtraction images show improved spatial accuracy when compared to a T1-weighted, anatomical reference image.  This results in improved accuracy in CBF quantification, which could potentially improve the assessment of disease-specific patterns indicated by regional CBF abnormalities.

Ulrich Katscher¹, Mussa Gagiyev¹, and Jakob Meineke^1
1Philips Research Europe, Hamburg, Germany

Deep gray matter nuclei (DGMN) in the human brain play an important role for numerous diseases like Alzheimer’s disease. Thus, the characterization of DGMN in the framework of multiple MR-based physiologic parameters (like magnetic susceptibility or electric conductivity) is expected to be helpful for understanding these diseases. This study investigates – to the best of our knowledge, for the first time - the electric conductivity of DGMN in healthy volunteers, reflecting the electrolyte content of these nuclei. Conductivity determination is boosted by utilizing geometry information obtained from susceptibility maps during conductivity reconstruction.

Jianxun Qu¹, Bing Wu¹, and Zhenyu Zhou^1
1MR Research China, GE Healthcare, Beijing, China, People's Republic of

This work investigates the gradient design scheme in ssASL labeling train to improve the labeling profile. Both numerical approach and MR studies were performed. Refocused labeling and unrefocused control could generate flatter labeling region compared to currently adopted method. This was verified in in-vivo MR study.

Alberto Merola¹, Esther AH Warnert¹, Michael A Germuska¹, Sharmila Khot^1,2, Daniel Helme², Lewys Richmond², Kevin Murphy¹, and Richard G Wise^1
1CUBRIC, Cardiff University, Cardiff, United Kingdom, ²Department of Anesthesia and Intensive Care Medicine, Cardiff University, Cardiff, United Kingdom

The acute effects of caffeine on haemodynamics are not well characterized across the brain with MRI. We aim at measuring these in a double-blind, crossover, placebo-controlled study on sixteen healthy, moderate caffeine consumers using mTI PASL acquisitions and a two-compartment ASL model. Results show spatial variations in the CBF and TAT response across grey matter at different levels of resolution (grey matter, ROI and voxel), with the latter presenting mixed directions. Moreover we demonstrate that great attention must be paid to physiological assumptions when modelling ASL data to estimate CBF in studies on drugs that affect brain haemodynamics.

Lennart Geurts¹, Alex Bhogal¹, Jeroen C.W. Siero¹, Peter R. Luijten¹, and Jaco J.M. Zwanenburg^1
1Radiology, UMCU, Utrecht, Netherlands

An increased blood flow pulsatility index in large cerebral arteries is a prognostic factor in stroke and has been linked to small vessel disease. Along with increased pulsatility, these patients show decreased hypercapnia induced cerebrovascular reactivity. We hypothesize that dilated vessels lose their ability to stretch and passively dampen the pulse pressure wave. The aim of this study was to shed light on how autoregulation influences the damping of the pulse pressure wave in small vessels. Our approach was to measure blood flow velocity and pulsatility changes in the perforating arteries of the white matter, during a hypercapnic breathing challenge.

Arjan D. Hendriks¹, Natalia Petridou¹, Catalina S. Arteaga de Castro¹, Mark W.J.M. Gosselink¹, Alessio Fracasso¹, and Dennis W.J. Klomp^1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands

By maximizing acquisition volume, using efficient semi LASER detection with editing and macro molecular nulling, GABA can be detected at high SNR within 3 minutes. GABA concentrations were measured in the visual cortex and in a phantom containing a known concentration of GABA. A bootstrapping method was used to determine the accuracy. The results indicate that the stability and fitting accuracy of the method is sufficient to detect concentration changes of GABA higher than 3% within a short scan time of less than 3 minutes. In resting state, GABA fluctuations up to 30% are found in in-vivo brain measurements.

Felipe Barreto^1,2, Nicholas Evanoff³, Donald Dengel³, Petr Bednarik^1,4,5, Ivan Tkac¹, Lynn Eberly⁶, Carlos Salmon², and Silvia Mangia^1
1CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Department of Physics, University of Sao Paulo, Ribeirao Preto, Brazil, ³School of Kinesiology, University of Minnesota, Minneapolis, MN, United States, ⁴Central European Institute of Technology, Masaryk University, Brno, Czech Republic, ⁵Department of Medicine, University of Minnesota, Minneapolis, MN, United States, ⁶Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States

Previous fMRI studies have demonstrated reduced evoked vascular responses during mild hypoxia, which might indicate smaller neuronal recruitment during activation. Here we used fMRS at 7T to quantify the effects of mild hypoxia on stimulus-induced metabolic changes during visual stimulation. Our preliminary findings obtained on 6 healthy volunteers show that mild hypoxia does not result in detectable differences of functional metabolic changes as compared to normoxia, consistent with similar functional energy demands in both conditions. Together with previous fMRI findings, our results suggest that mild hypoxia alters the neurovascular coupling, but does not result in smaller neuronal recruitment during activation.

Sankar Seramani¹, Xuan Vinh To¹, Sakthivel Sekar¹, Boominathan Ramasamy¹, Kishore Bhakoo¹, and Kuan Jin Lee^1
1Singapore Bioimaging Consortium, Singapore, Singapore

pCASL is a modified form of CASL where a short train of RF pulses reproduces CASL. pCASL sequence uses flow driven adiabatic pulses to invert the spin. The labeling efficiency of the pCASL sequence has a dependency on the velocity of the blood at the labeling. Phase contrast MRI (PCMRI) was used to measure the velocity of the blood at the labeling plane and to normalize the CBF value. In this study, we tested pCASL and PCMRI acquisition on a cohort of control rats vs. hyperglycemic rats and documented effect of varied labeling efficiency.

Tamar M van Veenendaal^1,2, Desmond HY Tse^1,3, Tom WJ Scheenen⁴, Dennis W Klomp⁵, Dominique M IJff^2,6, Paul AM Hofman^1,2,6, Rob PW Rouhl^2,6,7, Marielle CG Vlooswijk^2,6,7, Albert P Aldenkamp^2,6,7, Walter H Backes^1,2, and Jacobus FA Jansen^1,2
1Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, ³Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, Netherlands, ⁴Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands, ⁵Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ⁶Epilepsy Center Kempenhaeghe, Heeze, Netherlands, ⁷Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands

Many studies are performed to assess structural or functional brain connectivity. However, these studies do not provide direct information on neurochemical imbalances, which underlie abnormal neuronal functioning. In this study, the concept of ‘large-scale neurotransmitter networks’ is proposed. The spatial neurotransmitter network was assessed in fifteen healthy participants who underwent 7T MR spectroscopic imaging. The average glutamate and GABA concentrations were computed in thirty brain regions, which were considered connected if the concentrations showed a significant correlation over all thirty participants. Both glutamate and GABA networks showed small-world characteristics, but further exploration of this concept is currently ongoing.

Can Wu^1,2, Susanne Schnell², Ryan Kuhn³, Samantha E Schoeneman⁴, Amir R Honarmand², Michael Markl^1,2, and Ali Shaibani^2,3
1Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States, ²Department of Radiology, Northwestern University, Chicago, IL, United States, ³Department of Medical Imaging, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States, ⁴Rush Medical College, Chicago, IL, United States

Abnormal cerebral venous outflow patterns may cause severe cerebrovascular disease. We aim to investigate the relationships between cerebral venous outflow and arterial inflow and between cerebral arterial inflow and cardiac outflow in adult and children volunteers using 4D flow and 2D phase-contrast MRI. The results demonstrate significant discrepancies between cerebra arterial inflow and venous outflow with larger discrepancies in children than adults. Additionally, we observed a significantly association of cerebral and cardiac flow parameters with age.

Weiying Dai^1,2, Li Zhao¹, and David Alsop^1
1Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ²Computer Science, State University of New York at Binghamton, Binghamton, NY, United States

ASL global signal fluctuations, uniformly correlated across gray matter, may reflect globally correlated neural activity that would suggest a global resting network. However, physiological noise, such as cardiac and respiratory motion, could potentially contribute to the global signal fluctuations. Our results indicate that the systemic noise does not contribute to the ASL global signal fluctuation significantly. Global signal fluctuations are the dominant resting fluctuations of the ASL signal, suggesting a separate globally correlated resting state network in addition to those region-specific resting state networks.

Alex Bhogal¹, Jeroen C.W. Siero¹, Jaco Zwannenberg¹, Marielle E.P. Philippens², Peter R. Luijten³, and Hans Hoogduin^4
1Radiology, UMC Utrecht, Utrecht, Netherlands, ²Radiotherapy, UMC Utrecht, Utrecht, Netherlands, ³UMC Utrecht, Utrecht, Netherlands, ⁴Utrecht, Netherlands

We use native T1 (qT1) mapping to measure tissue T1 changes in response to precisely targeted, graded hyperoxic respiratory challenges at 7T.

Naoki Ohno¹, Tosiaki Miyati¹, Shinnosuke Hiratsuka², Shota Ishida³, Noam Alperin⁴, Satoshi Kobayashi¹, and Toshifumi Gabata^5
1Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan, ²Department of Radiology, Shiga University of Medical Science Hospital, Otsu, Japan, ³Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan, ⁴Department of Radiology, University of Miami, Miami, FL, United States,⁵Department of Radiology, Kanazawa University, Kanazawa, Japan

To quantify the effect of posture on intracranial condition, we assessed intracranial volume change (ΔICVC), pressure gradient (ΔPG), intracranial compliance index (ICCI), and apparent diffusion coefficient (ADC) change of the brain during the cardiac cycle (ΔADC) in head-down tilt (HDT) and horizontal supine positions. ΔPG was significantly increased on HDT compared with that in the horizontal supine position because of the intracranial pressure compensatory mechanism. However, there were no significant differences in other parameters between postures. ΔPG analysis in the HDT and horizontal supine positions makes it possible to evaluate intracranial conditions concerning the intracranial pressure compensatory faculty.

Trina Kok¹, Bernice Oh², Fatima Nasrallah¹, Mary Stephenson¹, Chin-Ian Tay Tony², Edwynn Kean-Hui Chiew², Johnson Fam², and Allen Eng-Juh Yeoh^2
1A*STAR-NUS Clinical Imaging Research Centre, Singapore, Singapore, ²National University Hospital, Singapore, Singapore

Dexamethasone (DEX) is commonly used at varying dosages to treat a range of diseases such as altitude sickness and leukemia. Current reports of neuropsychiatric and cognitive effects after DEX administration lack determination of the pathophysiological mechanism of such effects. This work aims to investigate the neurotoxic effects of DEX in healthy subjects by collecting MR structural and 1H spectroscopy data. Analysis showed a significant reduction in brain volume structures and hippocampal GABA/water (p < 0.02) ratio from start to end of DEX administration, which is recovered after a washout period.

Wen Cao¹, Yulin Chang¹, Suliman Barhoum¹, Zachary B Rodgers¹, Michael C Langham¹, Erin K Englund¹, and Felix W Wehrli^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

The OxFlow imaging approach allows simultaneous quantification of whole-brain venous oxygen saturation and total cerebral blood flow for the cerebral metabolic rate of oxygen. However, the current Cartesian rendition of the sequence is not ideal as the achievable temporal resolution is limited and needs to be chosen upfront. Here, we designed a golden-angle radial (GAR) encoding sequence that yields an effective temporal resolution of 1.29s and evaluated it in six subjects who underwent a paradigm of repeated breath-holds. Good agreement exists between the two methods but GAR provided superior SNR and better delineation of the temporal dynamics during the stimulus.

Jean-Christophe Brisset¹, Olga Marshall¹, Louise E Pape¹, Hanzhang Lu², and Yulin Ge^1
1Radiology, New York University School of Medicine, New York, NY, United States, ²Radiology, Johns Hopkins University, Baltimore, MD, United States

Cerebrovascular reactivity (CVR) measures the capacity of regulation of blood flow in response to vasoactive stimuli (e.g., CO2) via changes in cerebral arterial resistance. CVR is responsible for maintaining optimal blood flow to meet the energy demand by neurovascular coupling during neuronal tasks. The defected CVR can cause transient states of inefficient blood delivery during neural activity leading to subsequent neurodysfunction and degeneration. CVR is commonly measured with mild hypercapnia (5%CO2) ASL or BOLD MRI. The purpose of this study was to test the feasibility to measure CVR using hypercapnia MRI with quantitative susceptibility mapping (QSM) and T2-relaxation-under-spin-tagging (TRUST) techniques.

Petr Bednarík^1,2,3, Ivan Tkác¹, Dinesh Deelchand¹, Felipe Barreto^1,4, Lynn E. Eberly⁵, Shalom Michaeli¹, and Silvia Mangia^1
1CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Central European Institute of Technology, Masaryk University, Brno, Czech Republic, ³Department of Medicine, University of Minnesota, Minneapolis, MN, United States, ⁴Department of Physics, University of Sao Paolo, Ribeirao Preto, Brazil, ⁵Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States

With the goal of evaluating whether relaxation influences functional MRS (fMRS) results, we conducted fMRS experiments at 7T during visual stimulation using semi-LASER at 7T at long TE and short TR. The functional concentration changes of lactate (37%±6%) and glutamate (~5%±1%) observed here were consistent with previous results obtained at long TR and ultra-short TE. Small functional changes in signal intensity of NAA and Cr were also found, consistent with small changes in relaxations of those metabolites during visual stimulation.  

Jolanda M Spijkerman¹, Jill B de Vis¹, Esben T Petersen², Jeroen Hendrikse¹, and Jaco J M Zwanenburg^1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Centre for Functional and Diagnostic Imaging and Research, Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark

The oxygen tension in CSF and tissue is coupled, but may be easier to measure in CSF. This work investigated the effect of O₂ administration on the T₂ of CSF. In five subjects, T₂s were mapped in the lateral ventricles and the peripheral CSF during administration of a hyperoxic gas mixture (end-tidal O₂ level: 500mmHg). In the lateral ventricles no T₂ change was observed, in the periphery a significant T₂ reduction was found under O₂ administration (T₂=1.54s) compared to baseline (T₂=1.61s), showing the feasibility to use CSF relaxation parameter mapping to detect oxygen tension changes.

Jing Jiang¹, Xin Yang², Wenli Lai², Qiyong Gong¹, and Kaiming Li^1
1Department of Radiology, Huaxi MR Research Center, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, ²West China Hospital of stomatology, Sichuan University, Chengdu, China, People's Republic of

To investigate the neural mechanism of placebo effects in orthodontic pain, we conducted a fMRI study where twenty-three volunteers, under orthodontic pain induced by separators, were scanned without placebos and followed by another scan with placebos a month later. During both scans, participants were instructed to perform a bite (with maximum strength)/no-bite block design fMRI task. Compared with the non-placebo condition, the participants with placebos demonstrated significant reduced brain activities in multiple regions, including precentral gyrus, superior frontal gyrus, superior parietal lobule and supramarginal gyrus. This study may provide new insights into the neural mechanism of analgesia by placebo.

Jie Huang^1
1Department of Radiology, Michigan State University, East Lansing, MI, United States

Cerebral blood volume (CBV) is related with cerebral blood flow (CBF), and knowing this relationship may play an important role in quantitative BOLD-fMRI studies. A recent MRI study reports a varied CBV-CBF relationship both spatially and with sex. This study investigated the behaviors of CBV and CBF across the visual cortex at both rest and activation states, and the analysis showed a spatially inhomogeneous CBV-CBF relationship across the visual cortex.

Hou-Ting Yang¹, Yi-Jui Liu¹, Tzu-Cheng Chao^2,3, Wen-Chau Chen⁴, Teng-Yi Huang⁵, You-Chia Cheng¹, Hsiao-Wen Chung⁶, Chao-Chun Lin⁷, Chia-Wei Lin⁷, and Wu-Chung Shen^7
1Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan, ²Department of Computer Science and Information Engineering, National Cheng-Kung University, Tainan, Taiwan,³Institute of Medical Informatics, National Cheng-Kung University, Tainan, Taiwan, ⁴Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan, ⁵Department of Eletrical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ⁶Department of Eletrical Engineering, National Taiwan University, Taipei, Taiwan, ⁷Department of Radiology, China Medical University Hospital, Taichung, Taiwan

To investigate the relationships among regional activity of DMN in different hypercapnia affect using resting-state functional magnetic resonance imaging (rs-fMRI). 10 healthy males were enrolled in this study. A high-resolution T1WI image and BOLD-EPI were performed by a 3 Tesla MR scanner. The CO2 gas mixture (air, 3%, 5% and 7%) was given at the different hypercanpic for each experiment. Our results show that the functional connectivity of DMN is changed in hypercapnia. FC is slight change in 3% CO2 fractions and gradual reduction as the CO2 fraction increases.

Sourajit Mitra Mustafi¹, Chandana Kodiweera², Laura A. Flashman³, Thomas W. McAllister⁴, and Yu-Chien Wu^1
1Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ²Department of Psychological and Brain Sciences, Dartmouth College, Dartmouth, NH, United States, ³Department of Psychiatry, Dartmouth Hitchcock Medical Center and New Hampshire Hospital, Lebanon, NH, United States, ⁴Department of Psychiatry, Indian University School of medicine, Indianapolis, IN, United States

In the present study we used multi-shell Hybrid Diffusion Imaging (HYDI) to study white matter changes in the acute stage of mild traumatic brain injury (mTBI).  Nineteen mTBI patients and 23 trauma-controlled subjects were recruited and studied within 1 month of injury.  Non-parametric diffusion analysis, q-space imaging as well as parametric analyses including conventional DTI and novel neurite orientation dispersion and density imaging (NODDI) were used to analyze the HYDI data.  Only intra-axonal volume fraction of the NODDI model showed significant and diffuse decrease in white matter of the mTBI patients. 

Ping-Hong Yeh^1,2, Cheng Guan Koay², John Graner², Jamie Harper², Elyssa B. Sham², Jeannine Mielke², Tara Staver², Wei Liu², John Ollinger², Terrence Oakes², and Gerard Riedy^2
1Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States, ²National Intrepid Center of Excellence, Bethesda, MD, United States

Comorbid depression and PTSD are common among military traumatic brain injury population. This study assess brain structural and functional networks affected in military service members diagnosed with mild TBI. 

Daniel V. Olson¹, Melissa A. Lancaster^2,3, Michael A. McCrea^2,3, and L. Tugan Muftuler^2
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ³Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

The aim of this study was to characterize acute white matter changes within 24 hours and at 8 days following sport-related concussion in a group of young adult athletes. Both diffusion tensor and diffusion kurtosis tensor parameters were compared between concussed athletes and controls. The concussed group demonstrated widespread decrease in mean, axial, and radial diffusivity and increased axial kurtosis compared to the controls. Although diffusion effects became more extensive between the two time points, clinical measure differences between groups were nonsignificant at the 8-day follow-up. These findings may have significant implications for the clinical management of sport-related concussions.

Virendra R Mishra¹, Xiaowei Zhuang¹, Karthik Sreenivasan¹, Zhengshi Yang¹, Sarah Banks¹, Charles Bernick¹, and Dietmar Cordes^1
1Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States

Several cross-sectional MRI studies have shown structural differences in professional fighters but there has been no results reported in longitudinal studies of such active fighters. The professional fighters brain health study (PFBHS) is a longitudinal study of active professional fighters with age-matched healthy controls using multimodal MRI methods. In this study, we show that the features/biomarkers predicting cognitive decline at baseline are sensitive and specific over time in our cohort of longitudinal active fighters. Our study opens a new window to predict and monitor cognitive decline in patients with traumatic brain injuries.

Mehrbod Mohammadian^1,2, Timo Roine³, Jussi Hirvonen^2,4, Timo Kurki², and Olli Tenovuo^1,2
1Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland, ²Department of Clinical Medicine, University of Turku, Turku, Finland, ³iMinds-Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium, ⁴Department of Radiology, Turku University Hospital, Turku, Finland

We used a robust diffusion MRI approach to analyze global microstructural abnormalities in mild traumatic brain injury (mTBI) without confounding effects of complex fiber configurations. Microstructural properties of white matter skeleton were investigated, but only voxels with a single fiber orientation detected with constrained spherical deconvolution were included. In addition, whole-brain fiber tractograms were investigated. We studied 107 patients with mTBI and 28 age-matched control subjects. We found that fractional anisotropy was significantly decreased in mTBI, while mean diffusivity and radial diffusivity were increased. These differences were more significant when the analysis was restricted to single-fiber voxels.

Sohae Chung^1,2, Yadi Li³, Jacqueline Smith^1,2, Steven R Flanagan⁴, and Yvonne W Lui^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, United States, ³Department of Radiology, The Affiliated Ningbo Medical Treatment Center Lihuili Hospital of Ningbo University, Zhejiang, China, People's Republic of, ⁴Department of Rehabilitation Medicine, New York University Langone Medical Center, New York, NY, United States

Voxel-based morphometry (VBM) analysis has been used to detect morphometric changes of the GM after mild traumatic brain injury (mTBI). Spatially normalized and modulated GM density from VBM analysis is typically interpreted as GM volume. VBM is, however, sensitive not only to changes in volume but to variations in T1 relaxation. In this study, we investigated alterations in GM density using simulated images and VBM followed by an in vivo study of cortical GM morphometry using GM density and cortical thickness in mTBI patients and matched controls.

Neil G Harris¹, Derek R Verley², Boris A Gutman³, and Richard L Sutton^1
1Neurosurgery, UCLA, Los Angeles, CA, United States, ²Neurosurgery, University of California at Los Angeles, Los Angeles, CA, United States, ³Engineering, Radiology, & Ophthalmology, University of Southern California, Los Angeles, CA, United States

 Diffusion tensor imaging (DTI) is now widely used in both clinical and experimental research for studying pathology related to traumatic brain injury. However, studies report a wide range of DTI indices that are not easily ascribed to post-injury time-point, injury severity or developmental stage. In order to provide further information to help interpret these often complex changes we obtained DTI data before and after TBI using the well-known, clinically relevant rodent controlled cortical impact (CCI) model of TBI. In addition to the expected decreases in fractional anisotropy (FA) around the primary injury site which were associated with myelin breakdown and neurofilament loss, we found significant increases in FA within subcortical regions that were not associated with gliosis or fiber tract degeneration. Fiber tract density was decreased in regions of lowered FA but significantly increased only in subcortical regions associated with increased FA. High FA region seeded for tractography yielded significantly increased fiber length compared to pre-injury. These data provide additional insight into the interpretation of DTI indices following TBI.

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

Mild traumatic brain injury (mTBI) is a growing public health problem. Most patients recover quickly, but some patients may suffer from serious symptoms. In this study, we investigated white matter (WM) changes in mTBI in terms of compartment specific WM tract integrity (WMTI) metrics derived from diffusion kurtosis imaging (DKI), such as intra-axonal diffusivity (D_axon), extra-axonal axial and radial diffusivities (D_e,a and D_e,r), and axonal water fraction (AWF). The observed decreases in D_axon and D_e,a suggest that increased restrictions along the axons, both inside and outside, such as possible axonal beading, could occur acutely after injury.

Nastaren Abad^1,2, Abdol Aziz O. Ould Ismail^1,2, Ali Darkazali³, Jens T. Rosenberg¹, Cathy Levenson³, and Samuel Colles Grant^1,2
1Center for Interdisciplinary MR, National High Magnetic Field Laboratory, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, United States,³Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, United States

Traumatic Brain Injury (TBI) interferes with the functionality of the brain due to heterogeneous complications that continue after the initial trauma. As a result, stem cell therapy is viewed as a potential treatment approach that can be instituted during the chronic phase of TBI. This study employs Diffusion Tensor Imaging (DTI) to non-destructively probe the pathological impacts of endogenous Neural Progenitor Cells (NPC) and exogenous Mesenchymal Stem Cells (MSC) in a rodent model of TBI. This study represents the first investigation of the efficacy of MSC treatment in TBI and the potential synergistic effect of MSC and NPC.

Maged Goubran¹, Wei Bian¹, Brian Boldt¹, Mansi Parekh¹, David Douglas¹, Eugene Wilson¹, Lex Mitchell¹, Scott Anderson², Gerry Grant³, Huy Do¹, and Michael Zeineh^1
1Department of Radiology, Stanford University, Stanford, CA, United States, ²Sports Medicine, Stanford University, Stanford, CA, United States, ³Department of Neurosurgery, Stanford University, Stanford, CA, United States

While many cross sectional DTI studies have been performed for mild TBI in sports, very few longitudinal investigations have been performed. We present here a large longitudinal study assessing white matter integrity in high vs. low contact sports employing whole brain automated tractography and NODDI. We performed a tract-based analysis at baseline and longitudinally over 3 years, with both experiments localizing diffusion changes along the callosum forceps minor, left thalamic radiation and the superior longitudinal fasciculus. We have also shown that diffusion metrics correlate with cognition as assessed by the SCAT scores.

Bretta Russell-Schulz¹, Irene Vavasour², Jing Zhang², Alex MacKay^1,3, Shaun Porter⁴, Delrae Fawcett⁵, Ivan Torres⁵, William Panenka⁵, Lara Boyd⁶, and Naznin Virji-Babul^4
1UBC MRI Research Centre, Radiology, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁴Physical Therapy, University of British Columbia, Vancouver, Canada, ⁵Psychiatry, University of British Columbia, Vancouver, Canada, ⁶Physical Therapy, University of British Columbia, Vancouver, BC, Canada

Chronic traumatic brain injury (TBI) was examined using myelin water fraction (MWF) in global white matter and tracts for subjects undergoing intensive cognitive training (Arrowsmith Program) compared to age and gender matched controls. MWF was significantly lower in TBI subjects and correlations were found between MWF and cognitive scores of fluid and crystallized ability. However, after 3 months of cognitive training no significant differences were found in MWF in TBI subjects.

Yohan Boillat¹, Pierre-Louis Bazin², Kieran O'Brien^3,4, Mário João Fartaria de Oliveira^5,6, Guillaume Bonnier^1,6,7, Gunnar Krueger^6,8, Wietske van der Zwaag^1,9, and Cristina Granziera^1,6,7,10
1Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ³Siemens Healthcare Pty Ltd., Brisbane, Australia,⁴University of Queensland, St-Lucia, Australia, ⁵University of Lausanne, Lausanne, Switzerland, ⁶Advanced Clinical Imaging Technology Group, Siemens, Lausanne, Switzerland, ⁷Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, ⁸Healthcare Sector IM&WS S, Siemens Schweiz AG, Lausanne, Switzerland, ⁹Spinoza Centre for Neuroimaging, Amsterdam, Switzerland, ¹⁰Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States

The quantitative properties of the cerebellum were assessed by acquiring T₁ and T₂*contrasts at 7T and mapping these onto the cerebellar cortex. T₁ maps showed medial-lateral alternating stripes of different intensities while T₂* values were homogeneously distributed across the lobes. This study showed the heterogeneity of the cerebellar cortex in terms of tissue content, which in part parallels a well-established gene expression pattern.

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

The arcuate fasciculus (AF) is a group of association fibers consisting of 3 subcomponents that link perisylvian language centers in the frontal, temporal, and parietal lobes. The purpose of this study is to characterize the diffusion microstructural properties and functional outcomes of the cortical AF terminations in the right and left hemispheres. Multi-shell diffusion models were used to extract relative compartment densities, which were compared in cortical regions where AF fibers terminated. The results of this study show that perisylvian language centers exhibit differential cytoarchitecture that can be measured with in vivo MRI measures. 

Mara Cercignani^1,2, Giovanni Giulietti², Nick Dowell¹, Barbara Spano², Neil Harrison¹, and Marco Bozzali^2
1Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom, ²Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy

previous work suggested that the myelin volume fraction (MVF) is proportional to the macromolecular pool size ratio, F, derived from Magnetization Transfer (MT). However the proportionality constant seems to be dependent on the specific MT model, and requires histological validation. Here we propose a simple method based to derive such a constant.

Tsen-Hsuan Lin¹, Peng Sun¹, Yong Wang^1,2,3,4, and Sheng-Kwei Song^1,3,4
1Radiology, Washington University School of Medicine, St. Louis, MO, United States, ²Obstertic and Gynecology, Washington University School of Medicine, St. Louis, MO, United States, ³The Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States, ⁴Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States

The extent of axonal loss plays a significant role in irreversible neurological impairment in optic nerve crush (ONC). We detected significant 15% axonal loss in the absence of statistically significant atrophy using diffusion basis spectrum imaging (DBSI) 7 days after ONC in mice.   

Yolandi van der Merwe^1,2, Xiaoling Yang^1,3, Leon C. Ho^1,4, Yu Yu⁵, Christopher K Leung^6,7, Ian P. Conner^2,3, Seong-Gi Kim^1,8, Gadi Wollstein³, Joel S Schuman^2,3, Michael B Steketee³, and Kevin C Chan^1,3
1Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA, United States, ²Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Department of Electrical and Electronic Engineering, University of Hong Kong, Hong Kong, China, People's Republic of, ⁵Division of Biomedical Engineering, Hong Kong University of Science and Technology, Hong Kong, China, People's Republic of, ⁶University Eye Center, Hong Kong Eye Hospital, Hong Kong, China, People's Republic of, ⁷Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China, People's Republic of, ⁸Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Kuwon, Korea, Democratic People's Republic of

Glaucoma is a neurodegenerative disease that can cause irreversible blindness. Lowering intraocular pressure (IOP) is currently the only clinically approved treatment method for glaucoma, however the disease may still progress in some patients after lowering IOP. Citicoline has been suggested as a potential therapeutic for neurodegenerative diseases including glaucoma, but its neuroprotective effect remains incompletely understood. In this study, we determined the effects of oral citicoline treatment on visual function and white matter preservation in an experimental glaucoma model. The results show that citicoline treatment slowed the worsening of visual acuity and preserved white matter integrity along the visual pathway

Mara Cercignani^1,2, Giovanni Giulietti³, Nick Dowell⁴, Matthew Gabel⁴, Rebecca Broad⁴, P Nigel Leigh⁴, Neil Harrison⁴, and Marco Bozzali^3
1Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom, ²Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, ³Santa Lucia Foundation, Rome, Italy,⁴Brighton and Sussex Medical School, Brighton, United Kingdom

This paper investigates the variability of the g-ratio (the ratio of the inner to the outer diameter of a myelinated axon) as a function of age and gender in the healthy population. By combining magnetization transfer and diffusion MRI, the mean g-ratio of 20 white matter tracts was estimated, revealing no gender differences, and a systematic increase with age. Righ vs left hemisphere differences were also detected.

Cheuk Ying Tang¹, Victoria X Wang², Johnny C Ng², Stacie Deiner³, Rafael O'Halloran², Patrick McCormick³, Prantik Kundu², Lazar Fleysher², Angela Sanchez³, Kleopoulos Steven⁴, and Mark Baxter^5
1Radiology & Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ³Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁴Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁵Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States

The effect of general anesthesia was studied in brain white matter of healthy control elderly subjects.  DTI measures were compared between awake and general anesthesia conditions. We found significant transient decreases in Fractional Anisotropy and increases in Mean Diffusivities throughout the brain. 

Ouri Cohen^1,2, Frederick A. Schroeder ^1,2, and Jerome L. Ackerman^1,2
1Athinoula A. Martinos Center, Charlestown, MA, United States, ²Radiology, Massachusetts General Hospital, Boston, MA, United States

Construction of a loop-gap-resonator RF coil for MR microscopy of ex vivo mouse brains at 15T is described. The large signal obtained allowed acquisition of 20μm³ isotropic voxels, the highest resolution yet achieved in MR mouse brain imaging. Importantly, the high resolution allowed clear identification of multiple brain structures and will be of interest to researchers working with various mouse models. 

Se-Hong Oh¹, Stephen E. Jones¹, Arun Singh², and Mark J. Lowe^1
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ²Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, United States

We demonstrate a high-resolution ex-vivo globe image using 7T. With voxel size of 250μm isotropic resolution, detailed structures of the globe were clearly identified. Our results show that the high-resolution MR imaging is particularly useful in helping to visualize inner structure of eye-globe. Moreover, it is successfully demonstrated the sensitivity to choroidal melanoma. In addition, we have performed MRI scans using human globe specimens to investigate the contribution of fixation to the evolution of T₂ over time and measured SNR changes as function of the number of excitations to gain some insight into the optimal average number.

Marco Pagani^1,2, Mario Damiano¹, Alberto Galbusera¹, Sotirios A Tsaftaris^3,4, and Alessandro Gozzi^1
1Istituto Italiano di Tecnologia, Rovereto, Italy, ²Center for Mind and Brain Sciences, Rovereto, Italy, ³IMT - Institute for Advanced Studies, Lucca, Italy, ⁴Institute of Digital Communications, School of Engineering, The University of Edinburgh, Edinburgh, United Kingdom

We provide a detailed description of registration-based procedures for voxel based morphometry, cortical thickness estimation and automated anatomical labelling of the mouse brain. To illustrate our procedures, we described their application to quantify morphological differences in two inbred mouse strains characterised by different social behaviour. We show that our approach can reliably detect both focal and large scale gray matter alterations using complementary readouts. The operational workflows described here are expected to help the implementation of rodent morphoanatomical methods by non-expert users, and promote the use of these tools across the preclinical neuroimaging community.

Masaaki Hori^1,2, Nikola Stikov³, Ryuji Nojiri², Yasuaki Tsurushima², Katsutoshi Murata⁴, Keiichi Ishigame², Kouhei Kamiya⁵, Yuichi Suzuki⁵, Koji kamagata¹, and Shigeki Aoki^1
1Radiology, Juntendo University School of Medicine, Tokyo, Japan, ²Tokyo Medical Clinic, Tokyo, Japan, ³Ecole Polytechnique, University of Montreal, Montreal, QC, Canada, ⁴Siemens Japan, Tokyo, Japan, ⁵Radiology, The University of Tokyo, Tokyo, Japan

The purpose of this exhibit is to present the feasibility of MR g-ratio mapping for whole brain and cervical spinal cord using a 10 minute protocol. This protocol is appropriate for clinical use and provides reasonable image quality for clinical diagnosis. In vivo MR g-ratio mapping warrants daily clinical use as it has potential to provide additional information about WM microstructure and its changes in pathology.

Anna V Naumova^1,2, Andrey E Akulov³, Alexandr V Romashchenko ³, Oleg B Shevelev ³, Marina Yu Khodanovich ², and Vasily L Yarnykh ^1,2
1Radiology, University of Washington, Seattle, WA, United States, ²National Research Tomsk State University, Tomsk, Russian Federation, ³Institute of Cytology and Genetics, Novosibirsk, Russian Federation

This study provides methodological background for neuroimaging applications of fast 3D MPF mapping in ultra-high magnetic fields and demonstrates that MPF presents the most effective source of high-field brain tissue contrast. Unique contrast features, high spatial resolution, and the capability to provide quantitative information about myelination make MPF mapping an ultimate tool for small animal neuroimaging in high magnetic fields.

Francisco Lagos Fritz¹, Sean Foxley², Shubharthi Sengupta¹, Robbert Harms¹, Svenja Caspers³, Karl Zilles³, Desmond HY Tse¹, Benedikt Poser¹, Karla L Miller², and Alard Roebroeck^1
1Dept. of Cognitive Neuroscience, Faculty of Psychology & Neuroscience, Maastricht University, Maastricht, Netherlands, ²FMRIB Centre, University of Oxford, Oxford, United Kingdom, ³Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany

The investigation of whole human brains post mortem with large bore systems can achieve a resolution considerably superior to that achievable in-vivo. However, the achievable resolutions and contrast are limited, especially for diffusion MRI (dMRI), by gradient performance, non-optimized RF-coils, and RF-field inhomogeneity and decreasing T2 with increasing B0. Here we report on ultrahigh resolution (450µm) diffusion imaging of the whole human brain showing exquisite spatial definition. This is achieved using a specialized 9.4T 8Ch parallel transmit (pTx), 24Ch receive RF-coil and a diffusion weighted steady state free precession (dwSSFP) sequence extended with a kt-points excitation pulse for B1+ homogenization

James O'Callaghan¹, Holly Holmes¹, Nicholas Powell¹, Jack Wells¹, Ozama Ismail¹, Ian Harrison¹, Bernard Siow¹, Michael O'Neill², Emily Catherine Collins³, Karin Shmueli⁴, and Mark Lythgoe^1
1Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, ²Eli Lilly & Co. Ltd, Surrey, United Kingdom, ³Eli Lilly and Company, Indianapolis, IN, United States,⁴Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom

In this work, quantitative susceptibility mapping (QSM) and T2* mapping were used to investigate iron accumulation both in-vivo and ex-vivo in a mouse model of Alzheimer's Disease exhibiting tau pathology for the first time.  Magnetic susceptibility increases relative to controls were identified in grey matter and white matter brain regions and may indicate sensitivity to tissue iron content.  QSM in this mouse model may therefore provide a non invasive method by which to dissect the relationship between iron and tau pathology in Alzheimer's Disease.

Jason Langley¹, Jan Sedlacik², Daniel E Huddleston³, Xiaoping Hu¹, Jens Fiehler², and Kai Boelmans^4
1Department of Biomedical Engineering, Emory University & Georgia Tech, Atlanta, GA, United States, ²Department of Neuroradiology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, ³Department of Neurology, Emory University, Atlanta, GA, United States, ⁴Department of Neurology, University Medical Center Würzburg, Würzburg, Germany

Recent results found that the SN seen in neuromenalnin sensitive MRI and iron sensitive T₂-weighted contrasts is located in disparate spatial positions in controls. Since iron is known to be deposited in the SN after onset of Parkinson's disease(PD), we re-examine iron sensitive measurements with respect to these new findings in this abstract. Specifically, we find that the SN seen in T₂-weighted contrasts is enlarged in inferiorly and medially when compared to controls. Most of this discrepancy happens in the NM SN and we found the overlap to be an incredibly sensitive marker for PD (p<10^-15).

Darrell Ting Hung Li¹, Edward Sai Kam Hui¹, Queenie Chan², Nailin Yao³, Siew-eng Chua⁴, Grainne M. McAlonan^4,5, Shu Leong Ho⁶, and Henry Ka Fung Mak^1
1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, ²Philips Healthcare, Hong Kong, Hong Kong, ³Department of Psychiatry, Yale University, New Haven, CT, United States, ⁴Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong, ⁵Department of Forensic and Neurodevelopmental Science, King’s College London, London, United Kingdom, ⁶Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong

Abnormal iron accumulation in the brain may cause oxidative-stress-induced neurodegeneration, which is one of the hypothesis of nigral cell death in PD. It was also believed that non-motor symptoms of PD patients are associated with the increased of brain iron content. This study examined the iron concentration in several subcortical structures of PD patients with visual hallucinations by using the QSM technique. Higher magnetic susceptibility was observed in the hippocampus of this patient group. The result supported the hypothesis that hippocampal abnormality could induce visuospatial memory impairment which may be the cause of visual hallucination in PD patients.

Koji Kamagata¹, Kouhei Tsuruta², Taku Hatano³, Keigo Shimoji⁴, Masaaki Hori¹, Ayami Okuzumi³, Misaki Nakazawa², Syo Murata², Ryo Ueda², and Shigeki Aoki^1
1Department of Radiology, Juntendo University, Tokyo, Japan, ²Department of Radiological Sciences, Tokyo Metropolitan University, Tokyo, Japan, ³Department of Neurology, Juntendo University, Tokyo, Japan, ⁴Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

In this study, neurite-orientation dispersion and density imaging were used to estimate structural changes of neurites in the gray matter of the brain, which is the earliest pathological change in patients with PD. The results showed a significant decrease in the intracellular volume fraction in the right amygdala and right putamen in PD, suggesting a decrease in neurite density that may reflect actual pathological change. Given that NODDI could detect pathological changes at the earliest stages in PD, it may be useful for early diagnosis.

Gerd Melkus^1,2, Santanu Chakraborty^1,2, and Fahad A Essbaiheen ^1,2,3
1Medical Imaging, The Ottawa Hospital, Ottawa, ON, Canada, ²Radiology, University of Ottawa, Ottawa, ON, Canada, ³King Saud University, Riyadh, Saudi Arabia

Quantitative susceptibility mapping (QSM) was found as a useful method to evaluate neurodegenerative diseases such as Parkinson’s disease. For QSM reconstruction background field removed phase data is needed, but for retrospective studies only high-pass filtered data might be available. In this study we analyzed the influence of different high-pass filtered phase images on the susceptibility assessment for volunteers and Parkinson’s disease patients and compared the results to QSM estimation using background field removed phase data. With increasing high-pass filter strength consistently lower susceptibility results, but up to a certain filter strength differences in susceptibility can still be distinguished.

Wei-Tang Chang¹, Fiftarina Puspitasari¹, Ling-Yun Yeow¹, Hui-Chien Tay¹, Marta Garcia Miralles², Katrianne Bethia Koh², Liang-Juin Tan², Mahmoud POULADI^2,3, and Kai-Hsiang Chuang^1
1SBIC, A*STAR, Singapore, Singapore, ²TLGM, A*STAR, Singapore, Singapore, ³Department of Medicine, National University of Singapore, Singapore, Singapore

Huntington disease (HD) is an incurable neurodegenerative disease. Recently, memantine (MMT) was found to be effective delaying the progression of disease phenotypes in a mouse model of HD. Here we applied resting-state fMRI to evaluate functional connectivity in HD and the MMT treatment effect and its behavioral correlates. The results of forepaw stimulation reduced evoked responses though significance was hampered by large individual variation. Interestingly, functional connectivity outside of DMN, but not within DMN, was decreased by HD. With MMT treatment, the connectivity increased in general. The FC relevant to the behavioral test also showed behavioral correlates.

Yuguang Meng¹, Anthony W.S. Chan^2,3, and Xiaodong Zhang^1,3
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, United States, ³Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States

     This study examined the developmental changes of white matter integrity in rhesus monkey brains with the HD gene mutation using diffusion tensor imaging (DTI). Widespread developmental alterations are seen in striatum, and the frontal, motor, sensory and visual brain areas. The findings reveal the temporal-spatial evolution of abnormal white matter maturation during the development of the brain with the Huntington’s Disease, and suggest altered neural substrates associated with motor and cognitive dysfunctions in HD patients.

Jason Langley¹, Daniel E Huddleston², Michael Merritt¹, Xiangchuan Chen¹, Rebecca McMurray², Michael Silver², Stewart A Factor², and Xiaoping Hu^1
1Department of Biomedical Engineering, Emory University & Georgia Tech, Atlanta, GA, United States, ²Department of Neurology, Emory University, Atlanta, GA, United States

Inconclusive results from prior diffusion tensor imaging-based studies can be attributed to variability in location of regions of interest used to define the substantia nigra and its subcomponents. We apply recent findings from neuromelanin sensitive MRI to standardize regions of interest for the substantia nigra. Differences in fractional anisotropy and mean diffusivity were found in the neuromelanin sensitive substantia nigra but not in the substantia nigra defined in the b0 image.

Eung Yeop Kim¹, Yoon Ho Nam², Young Noh³, Young Hee Sung³, Byeong Ho Goh¹, Joon Hyung Ann¹, and Jongho Lee^4
1Radiology, Gachon University Gil Medical Center, Incheon, Korea, Republic of, ²Radiology, Seoul St. Mary Hospital, Seoul, Korea, Republic of, ³Neurology, Gachon University Gil Medical Center, Incheon, Korea, Republic of, ⁴Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of

Susceptibility map-weighted imaging (SMWI) improves both CNR and SNR in comparison with conventional SWI. In this work, we compared SMWI with MEDIC (a multi-echo GRE imaging that combines magnitude images via sum of squares) for nigrosome 1 imaging at 3T in terms of interobserver agreement and diagnostic performance in 74 subjects (44 with Parkinson’s disease). Two experienced and two less-experienced reviewers visually assessed both imaging sets separately. Compared with MEDIC, SMWI showed higher kappa values and larger AUCs, regardless of level of experience. As a result, nigrosome 1 imaging using SMWI significantly improved diagnostic performance as well as interobserver agreement.

Dinesh K Deelchand¹, James M Joers¹, Adarsh Ravishankar², Tianmeng Lyu³, Uzay Emir^1,4, Diane Hutter¹, Christopher M Gomez⁵, Khalaf O Bushara⁶, Christophe Lenglet¹, Lynn E Eberly³, and Gulin Oz^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²School of Physics and Astronomy, University of Minnesota, Minneapolis, MN, United States,³Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States, ⁴University of Oxford, Oxford, United Kingdom, ⁵Department of Neurology, University of Chicago, Chicago, IL, United States, ⁶Department of Neurology, University of Minnesota, Minneapolis, MN, United States

The goal of this study was to combine MRS with volumetric MRI to determine the sensitivity of these two techniques to onset and progression of neurodegeneration in patients with early-moderate spinocerebellar ataxia type 1. Subjects were scanned at baseline and followed up at ~18 and ~36 months at 3T. Both MRI and MRS measures were found to be more sensitive to disease progression than standardized clinical scores. This study shows that volumetric MRI was most sensitive to disease progression while MRS might be more sensitive to detect the disease’s early stage.

Rexford Newbould¹, Courtney Bishop¹, Antonio Martin-Bastida², and David Dexter^2
1Imanova Centre for Imaging Sciences, London, United Kingdom, ²Imperial College London, London, United Kingdom

A double-blind placebo-controlled clinical trial of an iron chelation therapy was performed in 25 subjects with Parkinson’s disease (PD) and 12 healthy matched controls.  Two MRI measures of brain iron at each of three visits at baseline, 3 months, and 6 months were derived from a high resolution 3D multiecho volume: T2* and QSM maps. T2* values significantly lengthened in six of nine pre-defined ROIs by the final visit in the highest dose group.  QSM values , however, did not change with treatment.  This differential trajectory between relaxation and susceptibility may result from ferritin’s complex relaxation behavior.

Karsten Mueller¹, Robert Jech^2,3, Cecilia Bonnet^2,3, Jaroslav Tintera⁴, Harald E Möller¹, Klaus Fassbender⁵, Jan Kassubek⁶, Markus Otto⁶, Evžen Ružicka^2,3, and Matthias L Schroeter^1,7
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, Prague, Czech Republic,³1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic, ⁴Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ⁵Clinic and Polyclinic for Neurology, Saarland University Homburg, Homburg, Germany, ⁶Clinic and Polyclinic for Neurology, University of Ulm, Ulm, Germany, ⁷Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany

Structural brain differences were investigated between patients with progressive supranuclear palsy (PSP) and healthy controls with T1-weighted images (MP-RAGE) acquired at four centers with different 3T scanners (Siemens). Using voxel-based morphometry, we found a major decline in gray matter density in brainstem, insula, striatum, and frontomedian regions that is in line with the current literature. Support-vector-machine classification provided a high sensitivity of disease detection when using relevant brain regions in feature selection.

Ulrika Roine¹, Timo Roine^2,3, Antti Hakkarainen³, Anna Tokola³, Marja H. Balk³, Minna Mannerkoski⁴, Tuula Lönnqvist⁵, and Taina Autti^3
1Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland, ²iMinds-Vision Lab, Department of Physics, University of Antwerp, Wilrijk (Antwerp), Belgium, ³HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, ⁴Child Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland,⁵Department of Child Neurology, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Juvenile neuronal ceroid lipofuscinosis (CLN3), is a progressive neurodegenerative lysosomal storage disease of the childhood, which manifests with loss of vision, seizures and loss of cognitive and motor functions, and leads to premature death. We investigated global and local white matter microstructure with diffusion MRI in 14 children with CLN3 imaged at two time points. Robust global analysis was performed using whole-brain tractography and white matter tract skeleton. Local microstructural abnormalities were investigated using tract-based spatial statistics. Significantly decreased fractional anisotropy and increased diffusivity values were found in subjects with CLN3 both at the global and local scale.

Sebastiano Galantucci¹, Federica Agosta¹, Elka Stefanova², Silvia Basaia¹, Martijn van den Heuvel³, Tanja Stojkovic², Elisa Canu¹, Iva Stankovic², Vladana Spica², Vladimir S. Kostic², and Massimo Filippi^1,4
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, ²Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Yugoslavia,³Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands, ⁴Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

To date, MRI biomarkers have been demonstrated extremely useful for detecting and monitoring the neurodegenerative processes. However, brain network analysis seems the most powerful approach to quantitatively describe the topological organization of the brain connectome even at early stages of neurodegenerative diseases.  This study provided promising biomarkers to detect features of neurodegeneration in PD-MCI, being able to distinguish it from PD without MCI. This study shows that the presence of subtle cognitive deficits not causing a dementia, produces a huge alteration of brain networks suggesting the importance of the study of connectomics in the investigation of neurodegenerative diseases.

Chiao-Chi Chen¹, Yi-Hua Hsu¹, Nai-Wei Yao¹, and Chen Chang^1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

The dopaminergic system possesses striking plasticity compensating for motor aberrations from neuronal loss. Little is known regarding the compensation mechanism during dopaminergic loss, preventing the aberration from being arrested and treated early. Here we present in vivo imaging evidence from functional magnetic resonance imaging showing that, after dopaminergic depletion, the dorsolateral striatum (DOLS) exhibited an early and transient vasodilation cluster in response to specific forepaw stimulation. Activation of DOLS NMDA receptors causes this vasodilation, protects dopaminergic fibers from denervation, and counteracts motor deficits. The findings have clinical implications for early detection and intervention in brain disorders such as Parkinson’s disease.

Chien-Yuan Eddy Lin¹, Wei-Che Lin², Pei-Chin Chen², Yung-Cheng Huang³, Nai-Wen Tsai⁴, Hsiu-Ling Chen², Hung-Chen Wang⁵, Tsu-Kung Lin⁴, Kun-Hsien Chou⁶, Meng-Hsiang Chen², Yi-Wen Chen², and Cheng-Hsien Lu^4
1GE Healthcare, Taipei, Taiwan, ²Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ³Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ⁴Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ⁵Department of Nuerosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ⁶Brain Research Center, National Yang-Ming University, Taipei, Taiwan

We examined the cerebral perfusion differences among 17 Parkinson’s disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used noncontrast arterial spin labelling MRI to assess the effects of dopaminergic therapies on perfusion in the patients. We demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing.

Jiuquan Zhang^1,2, Bing Ji^2,3, Zhihao Li², Jun Hu⁴, Jian Wang¹, Mingze Xu⁵, and Xiaoping Hu^2
1Department of Radiology, Southwest Hospital, Chongqing, China, People's Republic of, ²Department of Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA, United States, ³University of Shanghai for Science & Technology, Shanghai, China, People's Republic of, ⁴Department of Neurology, Southwest Hospital, Chongqing, China, People's Republic of, ⁵Department of Biomedical Engineering, Perking University, Beijing, China, People's Republic of

The corpus callosum (CC) involvement is a consistent feature of Amyotrophic lateral sclerosis (ALS), thus suggesting a pathopysiology of reduced interhemispheric neural connectivity. In the current study, we directly examined the interhemispheric functional and structural connectivities in ALS. In terms of functional connectivity, extensive alterations in voxel mirrored homotopic connectivity were found in ALS. With structural connectivity, while there were widespread reductions in DTI metrics, only the fiber probability index through CC subregion III in the ALS patients was significantly decreased compared with the controls. These findings provide further evidence for structural and functional interhemispheric connectivity impairment in ALS.

Yong Zhang¹, Naying He², Hua-Wei Lin², Ajit Shankaranarayanan³, Zhenyu Zhou¹, and Fu-Hua Yan^2
1MR Research China, GE Healthcare, Beijing, China, People's Republic of, ²Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, People's Republic of, ³GE Healthcare, Menlo Park, CA, United States

This preliminary study used voxel-mirrored homotopic connectivity (VMHC), a novel resting-state fMRI parameter to investigate inter-hemispheric functional connectivity in Parkinson’s Disease (PD) with asymmetric onset. Fifteen left side onset (LPD) patients, sixteen right side onset (RPD) patients and nineteen healthy controls were recruited for comparison. Both of LPD and RPD patients showed decreased VMHC in post-central gyrus responsible for motor functions. The decreased VMHC in the cuneus and middle occipital gyrus in LPD patients might affect visual processing function. For RPD patients, VMHC changes in the middle and superior frontal gyrus could be relevant to advanced cognitive impairment.

Chris Patrick Pflanz¹, Marina Charquero-Ballester², Adnan Majid³, Anderson Winkler¹, Emmanuel Vallee¹, Mark Jenkinson¹, Adam Aron³, and Gwenaelle Douaud^1
1FMRIB Centre, University of Oxford, Oxford, United Kingdom, ²Oxford, United Kingdom, ³San Diego, CA, United States

Huntington’s disease is a monogenetic, neurodegenerative movement disorder that is amenable to predictive genetic testing.  Here, we investigated whether longitudinal diffusion-weighted imaging of the basal ganglia could be used to detect early microstructural changes in participants with presymptomatic Huntington’s disease (preHD). We found the first results showing significant longitudinal changes in the microstructure of the basal ganglia within a preclinical HD population. We further showed that, while FA and MD might be less sensitive to longitudinal changes than volumetric measures, they provide mechanistic insights into the underlying physiopathological process that are complementary to the monotonic, non-specific changes in the volume of the basal ganglia.

Xu Li^1,2, Hongjun Liu^1,2, Richard P Allen³, Christopher J Earley³, Richard A.E. Edden^1,2, Peter B Barker^1,2, Tiana Cruz³, and Peter C.M. van Zijl^1,2
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States,³Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Possible brain iron deficiency was assessed using quantitative susceptibility mapping at 7T in restless legs syndrome (RLS) and analyzed with clinical measurements including IRLS severity score, serum iron, serum ferritin and periodic limb movement during sleep (PLMS). Using magnetic susceptibility as a brain iron index and compared to control group, significantly decreased iron was found in RLS patients in dentate nuclei and thalamus, and in substantia nigra in a subset of RLS patients with severe clinical symptoms with PLMS larger than 100 times per hour. Significant correlation between PLMS and brain iron was only found in substantia nigra in RLS.

Santanu Chakraborty^1,2, Gerd Melkus^1,2, Fahad Essbaiheen^1,2,3, David A Grimes⁴, and Tiago Mestre^4
1Medical Imaging, The Ottawa Hospital, Ottawa, ON, Canada, ²Radiology, University of Ottawa, Ottawa, ON, Canada, ³King Saud University, Riyadh, Saudi Arabia, ⁴Neurology, The Ottawa Hospital, Ottawa, ON, Canada

Parkinson disease (PD) continues to be diagnosed based on clinical findings. Recently, in SWI images, the loss of ‘swallow tail’ appearance in dorsolateral substantia nigra in PD patients yielded high diagnostic accuracy. In our study we measured susceptibility values using QSM in the ‘swallow tail’ area in seven Parkinson’s disease patients and compared to five control subjects. The susceptibility in the swallow tail area was higher in the PD group (0.072 vs. 0.058). This likely suggests increased iron deposition causing a masking effect that contributes along with dopaminergic neurons loss to the disappearance of the ‘swallow tail’ in PD patients.

Silvia Mangia¹, Philip Burton¹, Alena Svatkova^2,3, Igor Nestrasil⁴, Alejandra Sierra Lopez⁵, Karin Shmueli⁶, Lynn Eberly⁷, Michael Howell⁴, Paul Tuite⁴, and Shalom Michaeli^1
1CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States, ³Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic, ⁴Department of Neurology, University of Minnesota, Minneapolis, MN, United States, ⁵A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ⁶Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ⁷Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States

The idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson’s disease (PD), therefore by monitoring iRBD one can track the neurodegeneration of individuals that may progress to PD. Here we used a battery of MRI contrasts to characterize brain tissue properties such as microstructural integrity, iron loads, and functional connectivity in 10 iRBD, 10 PD and 10 age-matched healthy subjects. Rotating frame relaxation methods adiabatic T_1,2ρ and RAFFn, along with DTI and rsfMRI detected heterogeneous abnormalities in several subcortical structures of PD and iRBD subjects.

Zheng Zhong^1,2, Muge Karaman¹, Douglas Merkitch³, Jennifer Goldman³, and Xiaohong Joe Zhou^1,4
1Center for MR Research, Chicago, IL, United States, ²Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ³Neurological Sciences, Rush University Medical Center, Chicago, IL, United States, ⁴Radiology, Neurosurgery and Bioengineering, University of Illinois Hospital & Health Sciences system, Chicago, IL, United States

It has been known that the substantia nigra of brain stem shows structural abnormalities with the progression of Parkinson’s disease. While high b-value diffusion imaging has the potential to reveal such structural changes, single-shot EPI suffers from unwanted geometric distortion which may result in poor analysis of the diffusion data. In this study, we use a recently developed reduced field of view imaging technique and analyze the abnormalities occurring in the substantia nigra of the Parkinson’s disease patients by using the continuous-time random-walk (CTRW) model.

Ulrike Dydak^1,2, Ruoyun Ma^1,2, Nora Hernandez³, Johnathan P Dyke⁴, and Elan Louis^3,5,6
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States,³Department of Neurology, Yale School of Medicine, New Heaven, CT, United States, ⁴Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ⁵Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, New Heaven, CT, United States, ⁶Department of Chronic Disease Epidemiology, Yale School of Public Health, New Heaven, CT, United States

Whether current use of the medication primidone affects dentate γ-aminobutyric acid (GABA) concentrations is unknown. Yet, this may be an important confounder in studies of the pathophysiology of essential tremor (ET). Using the MEGA-PRESS J-editing sequence, we found no difference in dentate GABA levels between patients taking primidone and patients not taking primidone. Furthermore, there was no association between daily primidone dose and dentate GABA concentration. These data suggest that it is not necessary to exclude ET patients on primidone from MRS studies of dentate GABA concentration.

Yingjuan Wu¹, Robert J. Dawe², Arnold Moya Evia², Julie A. Schneider³, David A. Bennett³, and Konstantinos Arfanakis^2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Department of Biomedical Engineering, Illinois Institute of Technology, chicago, IL, United States,³Rush Alzheimer's Disease Center, Rush University Medical Center, chicago, IL, United States

The aims of this work were to: 1) longitudinally assess the diffusion anisotropy of various white matter regions measured with ex-vivo MRI, and 2) investigate the relationship between FA values measured in-vivo and ex-vivo on the same subjects. This work demonstrated that brain white matter diffusion anisotropy measured ex-vivo decreases with time postmortem, and that diffusion anisotropy measured ex-vivo is linearly related to the diffusion anisotropy measured in-vivo on the same subjects. Combination of ex-vivo MR diffusion anisotropy and histopathology may become an effective tool for the assessment of the neuropathologic correlates of structural brain abnormalities observed in-vivo.

June Chi-Yan Lo¹, Ruth Li-Fang Leong¹, Jesisca Tandi¹, and Michael Wei-Liang Chee^1
1Center for Cognitive Neuroscience, Duke-NUS Graduate Medical School, Singapore, Singapore

Although East Asia harbors the largest number of aging adults in the world, there is limited data on longitudinal changes in brain structure and its relationship with domain-specific cognition. We tracked changes in brain volume and 5 cognitive functions over 8 years among healthy older adults in the Singapore-Longitudinal Aging Brain Study. After adjusting for intracranial volume, demographic factors, and blood pressure, total cerebral atrophy was associated with faster decline in verbal memory. Hippocampal atrophy and ventricular expansion were associated with greater decline in verbal memory and executive functions. These findings clarify the relationships between age-trends in neurobiology and cognition.

Pui Wai Chiu¹, Edward S Hui¹, Queenie Chan², Raja Rizal Azman Raja Aman³, Raymond Chuen Chung Chang⁴, Raymond Chor Kiu Chan⁵, Leung Wing Chu⁶, 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, ³Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia, ⁴School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong, ⁵Neuropsychology and Applied Cognitive Neuroscience Laboratory, Chinese Academy of Sciences, Beijing, China, People's Republic of, ⁶Medicine, Queen Mary Hospital, Hong Kong, Hong Kong

Glutamatergic neurotransmission has an interesting role in aging. The anterior cingulate cortex(ACC) and posterior cingulate cortex(PCC) are focuses for aging research due to their implicated role in cognition. In this study, proton magnetic resonance spectroscopy was used to investigate the changes in glutamatergic neurotransmission during aging by measuring absolute Glx concentration([Glx]_abs) in ACC and PCC in a local Chinese cohort at 3.0T. Significant age-related increases of [Glx]_abs in ACC and PCC might indicate age-related alterations in glutamatergic neurotransmission. Significantly higher overall [Glx]_abs was found in ACC compared with PCC might be attributed to the abundant glutamatergic neurons in the forebrain.

Eniko Zsoldos¹, Nicola Filippini¹, Abda Mahmood¹, Archana Singh-Manoux², Mika Kivimäki², Clare Mackay¹, and Klaus P Ebmeier^1
1Psychiatry, University of Oxford, Oxford, United Kingdom, ²Epidemiology and Public Health, University College London, London, United Kingdom

Research presented discusses the cumulative effects of Framingham Stroke Risk profile in mid-life on structural brain integrity reduction in older life.

Jianli Wang¹, Xiaoyu Sun¹, and Qing X Yang^1
1Penn State College of Medicine, Hershey, PA, United States

We report an olfactory fMRI study of the aging effect on the functions of central olfactory system during normal adulthood and early aging. The smell identification function declined with age. Accordingly, the BOLD signal responding to odor stimulations was significantly decreased with age in bilateral DLPFC, left orbitofrontal cortex, and left insula. However, there was no significant age correlation was detected with the BOLD signal in the primary olfactory cortex. These results suggest that age-related olfactory functional decline in human brain is more prominent in the secondary and higher order central olfactory structures than the POC in early aging process. 

Maria Eugenia Caligiuri¹, Aldo Quattrone^1,2, and Andrea Cherubini^1
1Institute of Bioimaging and Molecular Physiology (IBFM), National Research Council, Catanzaro, Italy, ²Institute of Neurology, University Magna Graecia, Catanzaro, Italy

Diffusion-weighted MRI of the brain allows the assessment of tissue integrity at the microscale. The most commonly used technique to analyze diffusion-weighted data is diffusion tensor imaging (DTI), which relies on the reconstruction of the diffusion tensor at each MRI voxel by calculating its eigenvalues and eigenvectors. These quantities allow the estimation of scalar DTI maps measuring mean diffusivity (MD) and fractional anisotropy (FA), which are considered markers of structural tissue integrity. To date, DTI has been extensively used in the field of neuroimaging to study brain microstructural integrity in healthy subjects and patients with several different neurological conditions. However, despite the three-dimensional nature of the tensor, existing studies have focused on changes in DTI-derived scalar indexes, such as MD and FA, not considering the orientation of the principal eigenvector of the tensor, which could provide invaluable insight on the nature of tissue changes, but is still only used for color-coding FA maps for qualitative, visual purposes.

Eric T Peterson¹, Natalie M Zahr^1,2, Dongjin Kwon¹, Matthew Serventi¹, Cheshire Hardcastle¹, Edith V Sullivan², and Adolf Pfefferbaum^1
1Biosciences, SRI International, Menlo Park, CA, United States, ²Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

This work investigates the inter- and intra-session repeatability and the effects of age on intra voxel incoherent motion (IVIM) parameters. Atlas registration allowed for parcellation-based region specific brain analysis. A new and robust fitting approach reliably identified the perfusion fraction, diffusion, and pseudo-perfusion parameters from 15 healthy normal volunteers. The results show that IVIM is repeatable and that the perfusion fraction, diffusion, and pseudo-perfusion parameters are significantly higher in older than younger adults in several brain regions, most likely from perivascular CSF infiltration. This work serves to highlight how age is an important factor to consider when using IVIM.

Malgorzata Marjanska¹, J. Riley McCarten², Laura Hemmy², Dinesh K Deelchand¹, and Melissa Terpstra^1
1University of Minnesota, Minneapolis, MN, United States, ²Minneapolis VA Medical Center, Minneapolis, MN, United States

The goal of this work was to characterize differences in the concentrations of neurochemicals beyond tNAA, tCr, and tCho in the OCC and PCC regions of healthy young and elderly subjects. The key innovation was scanning at ultra-high field (7 T) at very short echo time. The observed differences are consistent with compromised neurons (NAA, NAAG, Glu and GABA), membrane turnover (PE and tCho), oxidative stress (lower GSH in the OCC), inflammation (mIns), altered energy metabolism (tCho and Glc), and changes in large molecules (Mac).

Eric C. Porges¹, Adam J. Woods¹, Richard A.E. Edden^2,3, Nicolaas A.J. Puts^2,3, Ashley D. Harris^4,5,6, Amanda Garcia¹, Huaihou Chen^1,7, Damon G. Lamb^1,8, John B. Williamson^1,8, and Ronald A. Cohen^1
1Aging and Geriatric Research, Institute on Aging, Center for Cognitive Aging and Memory, University of Florida, gainesville, FL, United States, ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Kennedy Krieger Institute, FM Kirby Center for Functional Brain Imaging, Baltimore, MD, United States, ⁴Department of Radiology, University of Calgary, Calgary, AB, Canada, ⁵CAIR Program, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada, ⁶Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ⁷Department of Biostatistics, University of Florida, Gainesville, FL, United States, ⁸Brain Rehabilitation and Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, United States

GABA levels measured with MRS have been associated with performance in numerous sensory and attention domains.  Here we demonstrate in a healthy aging cohort that frontal GABA levels are predictive of general cognitive function.  Furthermore, the previously reported age-related decrease in GABA levels continues into advanced age.

Mark David Meadowcroft^1,2, Jian-Li Wang², Carson J Purnell¹, Paul J Eslinger³, Elizabeth B Neely¹, David J Gill³, Megha Vasavada², Qing X Yang², and James R Connor^1
1Neurosurgery, The Pennsylvania State University - College of Medicine, Hershey, PA, United States, ²Radiology, The Pennsylvania State University - College of Medicine, Hershey, PA, United States,³Neurology, The Pennsylvania State University - College of Medicine, Hershey, PA, United States

Mutations associated with iron dysregulation in the brain include the H63D and C282Y HFE missense mutations and transferrin C2 mutation, all of which have been associated with development of neurodegenerative diseases.  Diffusion tensor metrics were further utilized to investigate the relationship between HFE/transferrin mutations and myelin integrity more precisely. The MRI data presented here demonstrate that cognitively normal H63D/C282Y HFE and transferrin C2 carriers have diffusivity changes in white matter compared to wild-type subjects. The observation that these alterations are located in late-myelinating frontal areas is hypothesized to be related to increased susceptibility within this region of HFE/Tf mutation carriers.

Xiao Luo¹, Yerfan Jiaerken¹, and MinMing Zhang^1
1Radiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, People's Republic of

The purpose of this research was to study the relationship of white matter hyperintensities (WMH) with cognitive performance in healthy elderly with different APOE genotypes. In total, 158 subjects were separated into 3 groups (ε2 carriers, ε4 carriers and ε3 homozygotes). Group differences of regional WMH volume were calculated. Subsequent correlation analysis between regional WMH burden and behavior data was performed. Detrimental effect of APOE ε4 allele on white matter structure was found while no protective effect of APOE ε2 was observed; WMH volume was significantly correlated with processing speed and executive ability, especially in APOE ε4 carriers.

Shin-Lei Peng^1,2, Xi Chen³, Yang Li¹, Karen Rodrigue³, Yamei Cheng⁴, Denise Park³, and Hanzhang Lu^1
1Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²China Medical University, Taichung, Taiwan, ³University of Texas at Dallas, Dallas, TX, United States, ⁴University of Texas Southwestern Medical Center, Dallas, TX, United States

Processing speed is a fundamental building block of cognition that declines reliably with age. Therefore, the goals of this study were to examine whether changes in cerebrovascular reactivity (CVR) to CO2 inhalation, a marker of cerebrovascular function, is associated with changes in processing speed. the results showed that, In elderly, but not young individuals, the rate of change in CVR over four years predicted decline in processing speed, indicating that declines in vascular brain health contribute to changes in the information processing speed in older but not young and middle-aged adults. 

Minjie Wu¹, Anand Kumar¹, and Shaolin Yang^1,2,3
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ²Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States, ³Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States

Using Magnetization transfer imaging (MT) and innovative multimodal analysis approach, the current study vertexwise mapped age-related changes of superficial white matter (SWM) from young adulthood to old age (30-85 years, N = 66).  Results demonstrated regionally selective and temporally heterochronologic changes of SWM MTR with age, suggesting that myelin change in SWM occurs at varied paces across the cortex. SWM MTR regions including the rostral middle frontal and parahippocampus followed inverted U-shaped trajectories, with protracted maturation till age 40-50 years and accelerating demyelination after age 60 years, while the primary motor, somatosensory and auditory SWM regions did not show age-related deterioration.

Rowa Aljondi¹, Patricia Desmond^1,2, Chris Steward^1,2, and Cassandra Szoeke^3
1The University of Melbourne, Melbourne, Australia, ²Department of Radiology, Royal Melbourne Hospital, Melbourne, Australia, ³Department of Medicine, The University of Melbourne, Melbourne, Australia

White Matter Hyperintesities (WMH) lesions on brain magnetic resonance imaging (MRI) are common findings in elderly people and contribute to cognitive impairments. Here we examine volumetric MRI measures of WMH volume in relation to neuropsychological measures of episodic memory, executive function, semantic memory and visuospatial abilities in 116 elderly women, their mean age 69 years. Linear regression analysis showed that greater WMH volume was correlated with lower performance on tests involving measures of executive function and visuospatial abilities. These results help elucidate the pathological process leading to cognitive decline in ageing.  

Pin-Yu Chen^1,2, Jeng-Min Chiou³, Ya-Fang Yang³, Yu-Ting Chen³, Yu-Ling Chang⁴, Yu-Chun Lo¹, Yu-Jen Chen¹, Yung-Chin Hsu¹, and Wen-Yih I. Tseng^1,2,5
1Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, ²Department of Life Science, National Taiwan University, Taipei, Taiwan, ³Institute of Statistical Sciences, Academia Sinica, Taipei, Taiwan, ⁴Department of Psychology, National Taiwan University, Taipei, Taiwan, ⁵Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

This study used template-based diffusion spectrum imaging (DSI) tractography to analyze the microstructural integrity of commissure fiber tracts, and applied functional data statistics to analyze the age effect on the tract integrity. The anterior commissure fibers were highly sensitive to the aging effect across the lifespan. The poster commissure fibers became sensitive to the aging effect after 60 years old. In contrast, the age effect of poster commissure fibers appears to occur after age of 60 years old. In conclusion, our study provides evidences for specific degenerative patterns of the commissure fibers tracts in normal ageing which may serve as a useful reference for neurodegenerative diseases.

Devasuda Anblagan^1,2, Maria C Valdés Hernández¹, Stuart J Ritchie^2,3, Benjamin S Aribisala^1,2, Natalie A Royle^1,2, Iona F Hamilton¹, David A Dickie¹, Susana Munoz Maniega¹, Mark E Bastin^1,2, Ian J Deary^2,3, and Joanna M Wardlaw^1,2
1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, ²Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom,³Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom

We tested whether there were coupled changes in hippocampal volume, T1, MTR, FA and MD and three broad cognitive domains (Verbal Memory, Working Memory, and Speed) in a large sample of community-dwelling non-demented adults at 73 and 76 years of age. Hippocampal volume, FA, MTR and T1 declined from age 73 to 76, while MD increased with age. Higher baseline MD was correlated with steeper cognitive decline in all three cognitive measures, but individuals with higher MD increases (i.e. more apparent deterioration in tissue integrity) also tended to show increases in Working Memory.

Roman Fleysher¹, Michael L Lipton¹, Tatjana Rundek², Richard Lipton³, and Carol Derby^4
1Department of Radiology, Albert Einstein College of Medicine, Bronx, NY, United States, ²Departments of Neurology and Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, United States, ³Saul R Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, United States, ⁴Saul R Korey Department of Neurology and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States

Normal aging is associated with changes both in micro-structure of white matter of the brain and in cerebral vasculature. We test the hypothesis that these processes are related by examining the association between fractional anisotropy (a di?usion tensor imaging measure of structural integrity) and  pulsitility index (a transcranial Doppler ultrasound measure of abnormal arterial flow) in 70 years old and older adults free of stroke and dementia. We identified clusters of significant correlations between the measures, supporting this hypothesis.

Ulrich Pilatus¹, Bianca Lienerth², Katharina Dietz³, Sina Schwarz⁴, Johannes Fleckenstein⁴, Silke Matura³, Tobias Engeroff⁴, Eszter Füzéki⁴, Valentina A. Tesky³, Elke Hattingen¹, Ralf Deichmann², Lutz Vogt⁴, Winfried Banzer⁴, and Johannes Pantel^3
1Neuroradiology, Goethe-Universität Frankfurt, Frankfurt, Germany, ²Brain Imaging Center, Goethe-Universität Frankfurt, Frankfurt, Germany, ³Institute of General Practice, Goethe-Universität Frankfurt, Frankfurt, Germany, ⁴Institute of Sport Sciences, Goethe-Universität Frankfurt, Frankfurt, Germany

In an interventional study changes in metabolic profiles (NAA/tCr, NAA/tCho) upon aerobic exercise were studied comparing two subgroups of volunteers who performed/not-performed supervised aerobic exercise. We observed a difference between both groups which can mainly be assigned to increased NAA/tCho in the group performing exercise.

Ludovica Griffanti¹, Philipp Stratmann^2,3, Michal Rolinski², Nicola Filippini^1,2, Eniko Zsoldos², Abda Mahmood², Mika Kivimäki⁴, Archana Singh-Manoux⁴, Klaus P. Ebmeier², and Clare E. Mackay^2
1FMRIB centre, University of Oxford, Oxford, United Kingdom, ²Department of Psychiatry, University of Oxford, Oxford, United Kingdom, ³Department of Informatics, Technische Universität München, München, Germany, ⁴Department of Epidemiology and Public Health, University College London, London, United Kingdom

This exploratory study aims to identify factors that may account for variability in functional connectivity within the basal ganglia resting state network (BGN) in healthy subjects, to help the development of an imaging biomarker for Parkinson’s disease. To this purpose we explored the relationship between functional connectivity measures derived from resting state fMRI and several demographic, behavioral and motor variables, in a large population-based sample of healthy elderly subjects, participating in the Whitehall II imaging sub-study.

Jared Hoffman¹, Vikas Bakshi², Ishita Parikh², Janet Guo³, Rachel Armstrong³, Steve Estes⁴, and Ai-Ling Lin^1
1Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, United States, ²University of Kentucky, Lexington, KY, United States, ³Lexington, KY, United States, ⁴Physiology, University of Kentucky, Lexington, KY, United States

Aging is the perhaps the greatest risk factor for the development of numerous health concerns, namely neurological diseases such as Alzheimer’s Disease (AD). Recently, certain variations in the gut microbiota have been implicated in the development of neurological disease. We hypothesize that alterations of the gut microbiome from age may cause dysregulated brain-gut communication, promoting inflammation and ultimately, disease. Indeed, our preliminary data found old mice to have a distorted gut microbiota, decreased cerebral blood flow and cognitive deficits, and distinct levels of certain brain metabolites than the young mice. 

Di Yang¹, Yaxin Zhu¹, Wenjing Zhang², Su Lui², and Zhihan Yan^1
1Department of Radiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China, People's Republic, Wenzhou, China, People's Republic of, ²Department of Radiology, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, People's Republic of China, Chengdu, China, People's Republic of

We investigated the impact of HPG-axis activity on brain morphometry. A total number of 52 subjects were recruited and scanned structural MRI.HPG-axis activated girls had less cortical thickness in the left inferiorparietal relative to comparison subjects. Meanwhile, gray matter volume was greater in the left precuneus in the focused group, relative to the control group. We found a positive correlation between circulating FSH and volume after excluded one outlier. This study demonstrates that there is some puberty-related maturation of the brain morphometry that is not confounded by age in the earlier stage of puberty.

Sonya Kaur¹, Stephanie Oleson¹, Evan Pasha², Carolyn Cassill¹, Hirofumi Tanaka², and Andreana Haley^1
1Psychology, University of Texas Austin, Austin, TX, United States, ²Kinesiology, University of Texas Austin, Austin, TX, United States

The number of individuals classified as obese or overweight has doubled in the last two decades . In addition to documented effects of obesity on physical health, obesity is also associated with significantly deleterious effects on the brain, including increased risk for dementia. It has been hypothesized that the negative effects of obesity on central nervous system functioning are driven by visceral fat, which is metabolically active. However, the mechanisms behind this relationship are poorly understood. Here, we propose to directly test the role of systemic inflammation as a mediator of the relationship between visceral fat and brain structure in middle aged adults

Dandan Huang¹, Hongyan Ni², Dan Liu², and Tianyi Qian^3
1First Central Clinical College, Tianjin Medical University, Tianjin, China, People's Republic of, ²Tianjin, China, People's Republic of, ³Beijing, China, People's Republic of

Several previous studies have tried to use MRS to investigate changes in brain function. In this study, we used a MEGA-PRESS sequence to measure the GABA and Glx concentration of normal controls, normal elderly controls, and patients with mild cognitive impairment and Alzheimer's disease. In ACC, the Glx showed significant differences between each groups, and the GABA showed significant aging effects in normal subjects.

Won-Jin Moon¹, Yeon Sil Moon², Jin Woo Choi¹, Won Sung Yoon¹, Ju Yeon Park¹, and Seol-Heui Han^2
1Department of Radiology, Konkuk University School of Medicine, Seoul, Korea, Republic of, ²Department of Neurology, Konkuk University School of Medicine, Seoul, Korea, Republic of

We found that the presence of DM is not associated with vacular risk factors on imaging and brain volumes, but associated with decreased susceptibility in left thalamus. Our results indicate that there may be a region-specific alteration of iron accumulation and iron metabolism in patients with both AD and DM.