Eun Soo Kim¹, and Seung-Koo Lee^2
1Department of Radiology, Hallym University College of Medicine, Pyeongchon, Pyeongchon, Korea, ²Department of Radiology, Yonsei University College of Medicine, Seoul, Seoul, Korea

Contrast perfusion and arterial spin label (ASL) are the latest techniques available for quantitative hemodynamic analyses. The ASL MR imaging modality is becoming more clinically relevant, given the recent significant improvements in the high-field MRI. goal of this project is to help a better understanding of ASL as a noninvasive and non-radiation tool for perfusion territory measurements and predict the prospect of ASL as perfusion study at children and to compare rCBF difference between contrast perfusion MRI and ASL MRI at moyamoya disease. The ASL MRI technique at moyamoya disease shows a significant estimation of rCBF of PCA territory compared with enhanced perfusion MRI.

JBM Warntjes^1,2, I Blystad³, A Tisell^1,4, AM Landtblom⁵, and P Lundberg^1,6
1Center for Medical Image Science and Visualization, Linköping, Sweden, ²Department of Medical and Health Sciences, Clinical Physiology, Linköping, Sweden, ³Department of Medical and Health Sciences, Radiology, Linköping, Sweden, ⁴Department of Medical and Health Sciences, Radiation Physics, Linköping, Sweden, ⁵Clinical Neuroscience, Linköping, Sweden, ⁶County Council of Östergötland, Department of Radiology UHL, Linköping, Sweden

In this study a previously reported magnetic resonance quantification method was applied to 16 healthy subjects and 16 patients diagnosed with Multiple Sclerosis. The absolute R1 and R2 relaxation rates and the proton density PD were retrieved in 11 different regions of the brain, carefully avoiding the visible MS lesions or diffuse hyper-intense areas in the patient group. Although the variation of the measured values increased in the MS group no significant difference was observed for normal appearing matter compared to the normal, healthy brain, except for the peritrigonial white matter.

Martina Absinta¹, Maria A. Rocca¹, Maria Pia Amato², Angelo Ghezzi³, Lucia Moiola⁴, Agnese Fiorino⁴, Pierangelo Veggiotti⁵, Andrea Falini⁶, Giancarlo Comi⁴, Massimo Filippi¹, and the MS and Neuroimaging Study Groups of the Italian Neurological Society^7
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ²Department of Neurology, University of Florence, ³MS Centre, Ospedale di Gallarate, ⁴Department of Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ⁵Department of Child Neurology and Psychiatry, Fondazione IRCCS Istituto Neurologico C Mondino, ⁶Department of Neuroradiology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ⁷.....

The patterns of regional abnormalities in the brain gray matter (GM) in pediatric multiple sclerosis (MS) patients according to their cognitive profile were assessed using voxel-based morphometry. Compared to controls and to cognitively preserved patients, cognitively impaired patients had atrophy of the bilateral precuneus, left (L) lingual gyrus, L inferior frontal operculum, L insula, L middle temporal gyrus, and L precentral gyrus. In pediatric MS patients, thalamic atrophy was significantly related to lesion volumes, while precuneus atrophy correlated with cognitive impairment, suggesting that the assessment of the regional distribution of GM atrophy contributes explaining cognitive deficits in these patients.

Maria A. Rocca¹, Paola Valsasina², Maria Pia Amato³, Martina Absinta², Angelo Ghezzi⁴, Lucia Moiola⁵, Agnese Fiorino⁵, Pierangelo Veggiotti⁶, Andrea Falini⁷, Giancarlo Comi⁵, Massimo Filippi², and the MS and Neuroimaging Study Groups of the Italian Neurological Society^8
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ²Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ³Department of Neurology, University of Florence, ⁴MS Centre, Ospedale di Gallarate, ⁵Department of Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ⁶Department of Child Neurology and Psychiatry, Fondazione IRCCS Istituto Neurologico C Mondino, Pavia, Italy, ⁷Department of Neuroradiology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ⁸.....

In this study, we assessed functional connectivity (FC) at resting state (RS) within and among cognitive networks in 34 patients with pediatric multiple sclerosis (MS) and 18 age- and sex-matched healthy controls. Decreased FC was found in regions of the posterior lobes, as well as in the cerebellum of the attention network, salience network (SN) and executive control network (ECN). Conversely, increased FC was found in frontal regions of the SN and of the default mode network (DMN). A decreased FC was associated with cognitive impairment, whereas increased FC was correlated with a lower structural damage.

Salil Soman¹, Deqiang Qiu², Michael Moseley², David Rex¹, Patrick D Barnes¹, and Kristen Yeom^1
1Pediatric Neuroradiology, Stanford University, Stanford, CA, United States, ²Radiological Sciences Laboratory, Stanford University, Stanford, CA, United States

Our work summarizes our experience performing multishot multiecho 3D GRE imaging of 50 pediatric patients using multiple TE values. We found that images with longer TE showed findings not visible on 2D GRE images, and that the shorter TE images still demonstrated findings when longer TE images were distorted by artifacts (dental hardware, motion, etc). This sequence is performed in approximately the same time as a standard SWI sequence, and has the potential to produce imaging for advanced techniques such as susceptibility mapping and T2* calculation. We believe this sequence can result in more clinically sensitive 3D GRE pediatric examinations.

Gareth Ball¹, James P Boardman^1,2, Paul Aljabar³, Anand Pandit¹, Tomoki Arichi^1,4, Nazakat Merchant^1,4, Daniel Rueckert³, A David Edwards^1,4, and Serena J Counsell^1
1Centre for the Developing Brain, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom,²Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, ³Biomedical Image Analysis Group, Department of Computing, Imperial College London, London, United Kingdom, ⁴Division of Neonatology, Imperial College London Healthcare NHS Trust, London, United Kingdom

Preterm birth is associated with a wide range of neurodevelopmental deficits and disruption of the thalamo-cortical system is thought to represent a key component of preterm brain injury. We describe a novel pipeline for comprehensively mapping thalamo-cortical connectivity in preterm neonates using probabilistic tractography. Using this technique we demonstrate that thalamo-cortical connectivity is significantly reduced in preterm infants at term-equivalent age compared to term-born controls.

Hou Xin¹, Li Xianjun², Gao Jie¹, Sun Qinli¹, Yu Bolang¹, Ed X. Wu³, Wan Mingxi², and Yang Jian^1,2
1Department of radiology, the First Affiliated Hospital of Medical College of Xi¡¯an Jiaotong University, Xi'an, Shannxi, China, ²Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shannxi, China, ³Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China

This study aimed to investigate the changes of term and preterm neonates with post-menstrual ages (PMA). 44 healthy neonates with PMA ranging from 33 to 42 weeks were enrolled. Diffusion tensor images were acquired and analyzed by tract-based spatial statistics (TBSS). 8 regions of centrum semiovale (CS), corpus callosum (CC), internal capsule (IC), external capsule (EC), optic radiation (OR), and anterior limb of internal capsule (ALIC) were selected. FA values generally increased while AD, RD, and MD values decreased significantly in most regions in term group. ALIC exhibited the lowest diffusion values. Moreover, the slope rates of SCC, CS, OR, EC with PMA were significant higher than those of other regions, indicating their rapid maturation.

Jeong-Won Jeong¹, Diane C Chugani², Tammy Hsia³, Vijay N Tiwari³, Harry T Chugani⁴, and Senthil K Sundaram^1
1Pediatrics and Neurology, Wayne State University, Detroit, MI, United States, ²Pediatrics and Radiology, Wayne State University, ³PET center, Wayne State University,⁴Pediatrics, Neurology, and Radiology, Wayne State University, Detroit, MI, United States

Diffusion tensor imaging (DTI) has the promise that it may aid the prognosis of language deficits in children with developmental delay (DD) and Angelman Syndrome (AS) by visualizing abnormally developed white matter in the perisylvian language network. Although our previous DTI studies [1,2] have suggested global impairment of white matter related to DD and AS by demonstrating quantitative reduction in diffusivity parameter such as fractional anisotropy (FA), determining whether a single DTI scan contains sufficient information to classify and make decision about an individual patient remains a critical challenge due to many experimental confounds, mainly depending on chronological age. The present study introduced new objective marker to quantify developmental maturation of the arcuate fasciculus based on the anterior-posterior (AP) component in colored coded orientation map which quantifies the first eigenvector of the diffusion tensor at every voxel. We first assessed a life-span maturation curve of new marker from healthy controls and examined its feasibility to discriminate the children with DD and AS from typically developing children without age-related confounds.

Katyucia de Macedo Rodrigues^1,2, Emma Ben-Avi², P Ellen Grant^2,3, Randy Gollub², Paul Caruso⁴, Kalpathy Krishnamoorthy⁵, and Lilla Zollei^2
1Radiology, Childrens Hospital Boston, Boston, Massachusetts, United States, ²Radiology, Martinos Center/MGH, Boston, Massachusetts, United States, ³Center for Fetal-Neonatal Neuroimaging & Developmental Science, Children's Hospital Boston, Boston, Massachusetts, United States, ⁴Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States, ⁵NEUROLOGY, Massachusetts General Hospital, Boston, Massachusetts, United States

Tractography analysis has been largely used to evaluate integrity of white matter, to locate specific tracts and to map connectivity. Different DWI acquisitions and post processing methods often make comparisons between studies challenging, with modification in a single parameter resulting in considerable changes in the final product. Because there is no consensus on how to post-process diffusion data, we sought to demonstrate the impact of maximum turning angle along tracts in four deterministic tractography reconstruction algorithms in pediatric population. Our results suggest optimal angle threshold may change when using different post-processing algorithms and may vary when analyzing different fiber bundles.

Ashok Panigrahy^1,2, Lisa Paquette³, Marvin D. Nelson², Jessica L. Wisnowski^2,4, and Stefan Bluml^2,5
1Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ²Department of Pediatric Radiology, Children's Hospital of Los Angeles, Los Angeles, California, United States, ³Division of Neonatology, Children's Hospital of Los Angeles, Los Angeles, California, United States, ⁴Brain and Creativity Institute, University of Southern California, Los Angeles, California, United States, ⁵Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States

Our study shows distinct metabolic differences in the CNS of neonates with congenital heart disease and prematurity including elevated myo-inositol in multiple regions of babies with congenital heart disease neonates and selective parietal white matter multi-metabolic hypermetabolism in the preterm neonates which may underlie patterns of poor cognitive outcome in these patients.

Alex M. Wong¹, Feng-Xian Yan², and Ho-Ling Liu^1,2
1Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ²Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan

We compared the 3D FSE pseudo-continuous ASL (PCASL) perfusion method with gradient-gradient (GE) and spin-echo (SE) dynamic susceptibility contrast (DSC) MRI in a group of 12 patients. In each patient, ratios of mean CBF in the cortical gray matter (GM) to deep white matter (WM) were obtained for the comparison. The results showed significant positive correlations between measurements from PCASL and either of the two DSC methods (r=0.72 (GE), 0.81 (SE), p < 0.05). The SE-DSC resulted in similar GM/WM ratios as PCASL, whereas GE-DSC yielded overestimated ratios which may be attributed to its greater sensitivity to large vessels.

Lindsay Walker^1,2, Marta Gozzi³, Audrey Thurm³, Babak Behseta³, Pooja Modi¹, Rhoshel Lenroot⁴, Susan Swedo³, and Carlo Pierpaoli^1
1PPITS/STBB/NICHD, NIH, Bethesda, MD, United States, ²CNRM, USUHS, Bethesda, MD, United States, ³NIMH, NIH, Bethesda, MD, United States, ⁴University of New South Wales, Sydney, Australia

Diffusion tensor imaging (DTI) shows promise for studying potential structural abnormalities in the brains of autistic children. However, the regional distribution of DTI findings in the literature is inconsistent across studies. We use DTI to investigate potential structural differences between the brains of autistic children as compared to age and gender matched typically developing children using high quality DTI data, and measure the regional magnitude of differences in various DTI metrics. While DTI is promising, caution must be exercised in interpreting between-group differences due to the small magnitude of the changes.

Zohra M Ahmadzai¹, Deanne K Thompson^1,2, Peter J Anderson^1,2, Jeanie Cheong^1,3, and Lex W Doyle^1,3
1Murdoch Childrens Research Institute, Melbourne, Victoria, Australia, ²University of Melbourne, Melbourne, Australia, ³Royal Women's Hospital, Melbourne, Australia

Smaller pituitary volumes may be a reflection of chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which is associated with prematurity, stress, anxiety and depression. Pituitary volumes were measured on T1 images of 186 extremely preterm and 139 full term 18 year olds. Preterm subjects had significantly smaller pituitary volumes than full term subjects, and females had larger pituitary volumes than males. Pituitary volume was not associated with postnatal corticosteroid therapy or perinatal brain injury. Smaller pituitary volume is indicative of chronic HPA-axis hyperactivity, and may account for the neuropsychiatric morbidities observed in preterm adolescents.

Bretta Russell-Schulz¹, Cornelia Laule^2,3, David Li³, and Alex MacKay^1,3
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada,³Radiology, University of British Columbia, Vancouver, BC, Canada

We used an extended Carr-Purcell-Meiboom-Gill sequence with echoes out to 1120ms to characterize longer T₂ times in the healthy corticospinal tract (CST). The CST intra-/extra-cellular T₂ peak was broadened compared to other white matter structures and often split into two distinct peaks. The intracellular and extracellular water environments in the CST had different T₂ times, causing the intracellular water peak to be pushed into the shorter myelin water T₂ regime and the extracellular peak to be pushed to higher T₂ times. The CST’s unique MR characteristics should be taken into consideration when being examined, especially when compared to pathological tissue.

Naoko Saito¹, Memi Watanabe², Osamu Sakai^2,3, and Hernan Jara^2,4
1Saitama International Medical Center, Hidaka, Saitama, Japan, ²Boston Medical Center, United States, ³Boston University School of Medicine, United States, ⁴Boston University School of Medicine, Boston, MA, United States

Purpose To study the proton density (PD) changes of the brain over the full human lifespan using quantitative MRI. Methods Forty-four subjects (0.5-87 years) scanned with the mixed-TSE pulse sequence were segmented into the whole brain tissues leading to the PD histograms. The histograms were modeled with Gaussian functions. Results PD of gray matter (GM) and white matter (WM) decreased from 0 to 20 years of age and remained approximately stable during adulthood period. During senescence period, PD of GM remained stable, while PD of WM increased. Conclusion Age-related PD changes of the brain have been studied.

Adolf Pfefferbaum^1,2, Torsten Rohlfing¹, Margaret J. Rosenbloom^1,2, and Edith V. Sullivan^2
1Neuroscience Program, SRI International, Menlo Park, CA, United States, ²Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States

To determine whether structural T1-weighted data acquired across MR field strengths could be merged, archival SPGR data acquired at 1.5T and 3.0T within 3 weeks in 114 adults were compared using intraclass correlation (ICC) computed on 24 cortical, subcortical, and CSF-filled volumes derived from an automated, unsupervised atlas registration/parcellation method. Application of regression correction functions for each region yielded significant ICC increases (mean improvement=.087; post-correction ICC range=.599 in globus pallidus to .998 in lateral ventricles). Thus, selected T1-weighted regional anatomical brain data can be reliably combined across 1.5T and 3.0T field strengths with the application of an appropriate correction procedure.

Antonios Makropoulos¹, Ioannis S. Gousias¹, Christian Ledig², Paul Aljabar², Ahmed Serag², Joseph V. Hajnal³, A. David Edwards¹, Serena J. Counsell¹, and Daniel Rueckert^2
1Centre for the Developing Brain, Imperial College London, London, United Kingdom, ²Biomedical Image Analysis Group, Department of Computing, Imperial College London, London, United Kingdom, ³Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom

The changes that occur in brain anatomy between early preterm and term age are significant and present challenges to an accurate automatic MRI segmentation of the preterm brain. Atlas-based techniques are amongst the most popular in brain MRI segmentation. However, when the atlases used deviate significantly from the subjects to be segmented, they result in inaccuracies. Within this context, we propose a Expectation-Maximization segmentation technique to propagate multiple labels, 50 in total, from manually segmented atlases around term to early preterm ages. The presented framework further adapts the priors to the target image so as to compensate for these inaccuracies.

Ho Jun Lee¹, and Eung Yeop Kim^2
1Radiology, Armed Forces Yangju Hospital, Yangju, Gyunggi-do, Korea, ²Radiology, Yonsei University College of Medicine, Seoul, Korea

There was a recent publication that there is interhemispheric asymmetry on the anterior margin of the Meyer's loop by means of perimetry. Only few studies have compared this by imaging. We measured the distance of the anterior margin of the Meyer's loop from the temporal pole (DTT) in both hemishperes, which appear as high SI distinguishable from adjacent structures on MPRAGE at a certain time window during myelination, in 47 infants. The measurements were significantly shorter in the left (left :22.5±2.7 mm, right: 24.0±2.4 mm). This is the first study to our knowledge to backup that there is interhemishperic asymmetry of DTT image wise, and will encourage validation by other investigators.

Matthew Borzage^1,2, Bimal Agrawal¹, John Wood^2,3, Ashok Panigrahy^4,5, Marvin D Nelson⁴, Istvan Seri^1,6, and Stefan Blüml^4,7
1The Center for Fetal and Neonatal Medicine and the USC Division of Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, Ca, United States, ²Viterbi School of Engineering, University of Southern California, Los Angeles, Ca, United States, ³Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, Ca, United States,⁴Radiology, Children's Hospital Los Angeles, Los Angeles, Ca, United States, ⁵Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa, United States, ⁶Keck School of Medicine, University of Southern California, Los Angeles, Ca, United States, ⁷Rudi Schulte Research Institute, Santa Barbara, Ca, United States

Blood oxygenation level dependent signal changes due to hypoxia and hyperoxia in healthy adults and a neonate were acquired. Exponential curves were fitted to parameterize the rate of change following FiO2 manipulations and the rates of change were compared. The rate of recovery from hypoxia depended on the subject scanned: adult recovery was markedly more rapid than the neonatal recovery. This preliminary data indicates that there may be substantial differences between the neonatal brain and adult brain when reacting to oxygen manipulations.

Hye Jin Jeong¹, So Yeon Shim², Joon Sup Jeong¹, Se Hong Oh¹, Sung Yeon Park¹, Young Bo Kim¹, and Zang Hee Cho^1
1Gachon University of Medicine and Science, Neuroscience Research Instiute, Namdong-gu, Incheon, Korea, ²Gachon University Gil Hospital, Department of Pediatrics, Namdong-gu, Incheon, Korea

Tract-based spatial statistics (TBSS) performed spatial normalization for group analysis in brain white matter. Due to the limited size of the mother's womb, twin has a high incidence of the prematurity. We aim to compare the development of brain white matter between preterm infants and twin infants at term gestational age using tract-based spatial statistics (TBSS). According to the voxel-wise analyses there was no significant FA difference between twin infants and preterm infants at term equivalent age.

Zhiqing Wu¹, Rita G. Nunes^1,2, Shaihan J. Malik¹, Georgia Lockwood Estrin¹, Emer J. Hughes¹, Christina Malamateniou¹, Serena J. Counsell¹, Mary A. Rutherford¹, and Joseph V Hajnal^1
1Robert Steiner MRI Unit,Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom, ²Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, Lisbon, Portugal

Fetal brain imaging with echo planar imaging (EPI) has extensive applications, notably Diffusion Tensor Imaging. EPI brain imaging in adults and children normally employs the smallest field of view combined with parallel imaging to reduce distortion and mitigate signal losses from T2&T2* decay. The balance of issues is quite different for fetal applications: the fetal brain has much longer T2&T2* and there is no air or mineralised bone within the womb to produce localised B0 anomalies, but there is large scale fetal motion. We have explored the implications of these factors to achieve improved Slice-to-Volume reconstruction (SVR) using EPI.

Alex Smith¹, Michael De Bellis^2,3, and Nan-kuei Chen^1
1Brain Imaging and Analysis Center, Duke University, Durham, North Carolina, United States, ²Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States, ³Healthy Childhood Brain Development and Developmental Traumatology Research Program, Duke University Medical Center, Durham, North Carolina, United States

Fractional Anisotropy, as measured by DTI, increases with age and intelligence during normal development, however, this is understudied in developing adolescents. DTI datasets from healthy children were acquired, and a voxelwise analysis was performed contrasting age and IQ against FA. Significant clusters were discovered in the corpus callosum and splenium correlating with age, while significant clusters were discovered globally when correlating with IQ. These findings suggest that white matter integrity increases with age and IQ in adolescence, and can have important implications later in life.

Jill B De Vis¹, Manon JNL Benders², Linda S de Vries², Floris Groenendaal², Karina J Kersbergen², Thomas Alderliesten², Jeroen Hendrikse¹, and Esben T Petersen^1
1Radiology, University Medical Center, Utrecht, Utrecht, Netherlands, ²Neonatology, University Medical Center, Utrecht, Netherlands

Human brain maturation is incomplete at birth. During development the brain undergoes anatomical and functional maturation. This includes proliferation of the neurones, their migration to specific sites and myelin formation. These processes are reflected in local cerebral energy demand. In the past, Positron Emission Tomography has been used to study glucose metabolism during different developmental stages in infants. Arterial Spin Labeling MRI provides us with a non-invasive way to assess Cerebral Blood Flow in different brain regions and can be used as well to study neonatal brain development.

Francesco Carletti^1,2, Shannon H. Kolind^1,3, James B. Woolley², Rocio Perez-Iglesias², Matthew R. Broome⁴, Elvira Bramon², Louise Johns⁵, Steve C.R. Williams¹, Philip K. McGuire², and Gareth J. Barker^1
1Department of Neuroimaging, Center for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, United Kingdom, ²Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom, ³FMRIB Centre, University of Oxford, Oxford, United Kingdom, ⁴Health Science Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom, ⁵Department of Psychology, Institute of Psychiatry, King's College London, London, United Kingdom

Structural neuroimaging studies indicate that psychotic disorders such as schizophrenia are associated with white matter (WM) abnormalities, and some of these changes are evident before the onset of psychosis. We investigated a cohort at 'ultra-high-risk' (UHR) for developing psychosis using diffusion tensor imaging (DTI) by comparing individual subjects’ data to a population based mean and standard deviation (z-score mapping). Our aim was to assess, prior to psychosis onset, whether z-score mapping can detect at the individual level FA changes in (i) UHR compared to controls (ii) UHR subjects who subsequently became psychotic versus those who did not.

Mark S Brown¹, Peter Teale², Dan Collins², Bryce Pasko², Debra Singel³, Don C Rojas², and Martin Reite^2
1Radiology, University of Colorado Denver, Aurora, Colorado, United States, ²Psychiatry, University of Colorado Denver, Aurora, Colorado, United States, ³Brain Imaging Center, University of Colorado Denver, Aurora, Colorado, United States

Magnetoencephalography (MEG) recordings of neural oscillations of the gamma band (~40 Hz) phase locking factor (PLF) yield a number that measures how well the response coincides with the stimulus in time. Schizophrenic subjects show impaired tracking ability compared to controls. We have measured the GABA levels in the temporal lobe (auditory cortex) of schizophrenics using J-edited 1H MRS and correlated them with the PLF. Schizophrenics show a negative correlation with PLF compared to the positive correlation exhibited by controls. The results suggest that the impairment is not due to lower levels of GABA, but rather impaired utilization by the schizophrenics.

Gwang-Won Kim¹, Moo-Suk Lee², Heoung-Keun Kang³, Tae-Jin Park⁴, Jong-Chul Yang⁵, Gyung-Ho Chung⁶, and Gwang-Woo Jeong^3
1Research Institute of Medical Imaging, Chonnam National University Medical School, Gwangju, Chonnam, Korea, ²Psychiatry, Chonnam National University Hospital,³Radiology, Chonnam National University Hospital, ⁴Psychology, Chonnam National University, ⁵Psychiatry, Chonbuk National University Hospital, Korea, ⁶Radiology, Chonbuk National University Hospital

Cognitive deficits in schizophrenia are associated with dysfunction of the lateral prefrontal cortex closely related to delayed-response working memory (WM). Despite recent studies in identifying the neural circuitry contributing to delayed-response WM, the correlation between brain volume change and impairment of the inhibition control in patients with schizophrenia have not yet been completely specified. The purpose of this study was to discriminate the brain activation patterns associated with the effect of distraction during the working memory maintenance for the human faces in the healthy controls and patients with schizophrenia by using a function magnetic resonance imaging (fMRI), and further to assess the relationship between changes of the activation patterns due to impairment of the inhibition control and reduction of the volumes of the corresponding brain areas in patients with schizophrenia.

Mark S Brown¹, Sarah Steinmetz², Debra Singel³, Susan Hepburn², and Don C Rojas^2
1Radiology, University of Colorado Denver, Aurora, Colorado, United States, ²Psychiatry, University of Colorado Denver, Aurora, Colorado, United States, ³Brain Imaging Center, University of Colorado Denver, Aurora, Colorado, United States

The excitation/inhibition imbalance (EI) theory of the pathophysiology of autism spectrum disorders (ASD) proposes that high ratios of excitatory to inhibitory neuronal processes could explain the ASD phenotype. Evidence for GABAergic inhibitory deficits has been of interest for some time and is supported by a significant body of evidence. We measured levels of GABA in the left auditory cortex using J-edited 1H-MRS in subjects with ASD and compared them to healthy controls. The results show significantly reduced levels of GABA in the ASD group. These results, combined with our previously reported elevated glutamate levels, provide support for the EI theory.

Rhoshel Lenroot^1,2, Pui Ka Yeung², Gloria Roberts¹, Clare McCormack¹, Michael Breakspear^1,3, Melissa Green¹, Andrew Frankland¹, Adam Wright¹, Phoebe Lau¹, Florence Levy¹, Herng Chan¹, Dusan Hadzi-Pavlovic¹, and Philip Mitchell^1
1University of New South Wales, Randwick, NSW, Australia, ²Neuroscience Research Australia, Randwick, NSW, Australia, ³Queensland Institute of Medical Research

Characterization of brain morphometry in individuals at elevated genetic risk for Bipolar Affective Disorder may illuminate early stages of the disorder and identify potential endophenotypes. Structural MRI images were acquired in 85 adolescents and young adults at elevated genetic risk for BPD and 84 matched control subjects. Brain volumes, cortical surface area and thickness were examined using an automated method. At-risk subjects had increased brain volumes and surface area, including regions such as the anterior cingulate and insula, but cortical thickness was not different. These finding suggest surface area may be a useful endophenotype for genetic studies of BPAD.

Fernando Emilio Boada¹, Vincent Lee¹, Yongxian Qian¹, Mary Phillips², and David Kupfer^2
1Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States

Regional Differences in Sodium Content between Euthymic Bipolar Subjects and Normal Controls were studied using High Resolution Sodium MRI at 7T. Results support the existence of statistically significant differences in sodium concentration in the basal ganglia but not in the average total brain concentration.

Anant Bahadur Patel¹, Pandichelvam Veeraiah¹, Judith Noronha¹, Puneet Bagga¹, and Arvind Kumar^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Mechanisms responsible for the abnormal glutamate and GABA level in the brain of depressed patients remain to be understood. Current study investigate cerebral metabolism in prefrontal cortex of depressed and resilient mice. Level of glutamate, aspartate, taurine and choline was found to be decreased in depressed mice while resilient mice showed increased GABA without any change in other neurometabolites. Depressed mice are associated with reduced glutamatergic and GABAergic activity.

Heath R. Pardoe¹, and Graeme D. Jackson^1,2
1Brain Research Institute, Florey Neuroscience Institutes, Melbourne, Victoria, Australia, ²Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia

Medication is the standard treatment option to reduce seizures associated with epilepsy. Although a number of studies have used magnetic resonance imaging to investigate the morphometric properties of the epilepsy brain, very few have systematically investigated the relationship between anti-epileptic medication and brain structure. Some studies have reported neuroanatomical changes associated with acute ingestion of sodium valproate, a commonly used anti-epileptic medication. In this study we use morphometric analysis of structral MRI to determine if sodium valproate, administered in clincal doses, has any effect on brain structure.

Alexander Gussew¹, Stefan Smesny², Patrick Hiepe¹, Reinhard Rzanny¹, and Jürgen R. Reichenbach^1
1Medical Physics Group, Department of Diagnostic and Interventional Radiology I, Jena University Hospital, Jena, Thuringia, Germany, ²Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Thuringia, Germany

³¹P/¹H CSI data and high resolution structural MR images were acquired in brains of non-medicated first episode schizophrenic patients and age matched healthy controls to investigate metabolic and morphological processes, which underlie the neurodegenerative changes occurring during the manifestation of schizophrenia. Significant group differences of brain white matter contents were detected frontal brain regions. Further, significant increased levels of NAA, glutamate, creatine and choline as well as phosphodiesters and phosphocreatine were observed in the anterior cingular cortex of patients indicating for elevated neurotransmission, membrane turnover and energy demand in this brain area.

Francesco Giorlando¹, Paul Fletcher², and Peter Brotchie^3,4
1Psychiatry, University of Melbourne, Geelong, VIC, Australia, ²Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ³Radiology, Barwon Medical Imaging, The Geelong Hospital, Geelong, VIC, Australia, ⁴The University of Melbourne, Melbourne, VIC, Australia

An fMRI trial of temporal dissociation induced by ketamine was conducted in 27 volunteers. The study used an event related paradigm and was placebo controlled. The Temporal Order Assessment task was the main measure of interest. Significant dorsal anterior cingulate cortex and inferior frontal cortex activation was found with inverted temporal judgements. Ketamine administration was associated with increased left temporo-parietal-occipital junction activity. The results are discussed with relation to the cortico-limbic theory of dissociation and the implications for theories of temporal perception.

Dirk Ernst Cleppien¹, Alexander Sartorius², Claudia Falfan-Melgoza¹, Natalia Gass¹, Lei Zheng³, and Wolfgang Weber-Fahr^1
1NeuroImaging, Central Institute of Mental Health, Mannheim, Germany, ²Clinic of Psychiatry and Psychotherapie, Central Institute of Mental Health, Mannheim, Germany,³Experimental Radiation Oncology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany

Haloperidol is a widely used antipsychotic drug with potent dopamine D2 receptor antagonistic properties. To understand its impact on the striatum high-resolution regional cerebral blood volume (rCBV) mapping with magnetic resonance imaging was performed in 10 rats. The standardized rCBV maps show areas of activation corresponding well with the findings in the literature under c-fos activation. A deactivation in the central caudate-putamen could corroborate findings of a T2* signal loss in some parts of the CPu. This underlines the importance of high-resolution functional rCBV measurements covering larger parts of the brain.

Edith V. Sullivan¹, Eva M. Müller-Oehring^1,2, Anne-Lise Pitel¹, Sandra Chanraud¹, Ajit Shankaranarayanan³, David C. Alsop^4,5, Torsten Rohlfing², and Adolf Pfefferbaum^1,2
1Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States, ²Neuroscience Program, SRI International, Menlo Park, CA, United States, ³GE Healthcare, Menlo Park, CA, United States, ⁴Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁵Radiology, Harvard Medical School, Boston, MA, United States

3D whole-brain pseudo-continuous arterial spin labeling (PCASL) measured cerebral blood perfusion (CBF) in alcoholics and controls while resting, task-engaged, and resting again. Based on bilateral, normalized CBF, both groups showed a default mode network (DMN) pattern (high activation for rest, low for task, return to high CBF in second rest) in medial frontal, temporal, calcarine, insular, cingulate, posterior precuneus cortices and hippocampus-amygdala, and a task-activated pattern (high task activation, low for rest) in cerebellum, parietal, occipital, middle precuneus cortices. Alcoholics differed from controls in CBF levels of insula and the rest-task-rest CBF pattern for anterior precuneus, regions involved in addiction.

Binquan Wang^1,2, Ping-Hong Yeh^1,2, Wei Liu^1,2, John Graner^3,4, Haiying Tang^2,5, Hai Pan^1,2, Dominic E Nathan^1,2, Rachel Wolfowitz⁴, Jamie Harper⁴, John Ollinger⁴, Terrence R Oakes^2,4, and Gerard Riedy^4,5
1Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States, ²Center for Neuroregenerative Medicine, Bethesda, MD, United States,³National Capital Neuroimaging Consortium, Bethesda, MD, United States, ⁴National Intrepid Center of Excellence (NICOE), Bethesda, MD, United States, ⁵Uniformed Services University of The Health Sciences of The Health, Bethesda, MD, United States

T2* mapping of combat-related TBI patients were investigated. The T2* mapping demonstrates the advantage to detect the brain lesions as previous studies. And both of voxel wise and ROI analysis shows TBI patients had significantly longer T2* relaxation time than healthy controls. And the positive relationship was illustrated by the regression between T2* and neurobehavioral symptoms. Our findings may be used to predict the clinical symptoms of military-related TBI patients

Ji-Young Kim¹, Jeehye Seo², Hui-jin Song², Seong-Uk Jin², Jang Woo Park², Moon Han², Jong Su Baeck², Hee-Kyung Kim³, and Yongmin Chang^4
1School of Medicine, Kyungpook National University, Daegu, Jung-gu, Korea, ²Medical & Biological Engineering, Kyungpook National University, Korea, ³Applied Chemistry, Kyungpook National University, Korea, ⁴Molecular Medicine, Kyungpook National University, Korea

Stroke patients with hand function in severe hemiplegic are known to be determined their prognosis at acute period of stroke. Brunnstrum motor recovery stage (BMS) and motor evoked potential (MEP) have been used to predict prognosis in stroke patients well. Using the BMS and MEP, stroke patients who have no MEP of affected hand or no hand movement with BMS 1 in 4 weeks from onset of stroke were usually regarded as that with poor prognosis. Nevertheless, most patients regarded as poor prognosis could recover their hand function. Recent researchers revealed functional connectivity of homologous primary motor cortex as a prognostic factor in stroke patients. The aim of this study is to (1) compare inter-hemispheric functional connectivity scores with in homologous M1 among stroke patients groups which showed different recovery patterns by means of resting state fMRI and (2) find good prognostic phenomeni to severe hemiplegic stroke patients who had no hand movement with BMS 1 and MEP response by means of fMRI with passive movement.

Feng-Xian Yan¹, Tsong-Hai Lee², Ho-Fai Wong³, and Ho-Ling Liu^1,3
1Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ²Department of Neurology and Stroke Center, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taoyuan, Taiwan, ³Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan

This study aimed to investigate the default-mode network (DMN) and task-positive network (TPN) connectivity changes in patients with unilateral internal carotid artery stenosis before and after carotid stent placement. Sixteen patients underwent resting-state (RS) fMRI and DSC perfusion MRI scans one week before and six months after stenting. RS functional images were analyzed with seeds defined as a spherical ROI within PCC and a PCC mask. This study found impaired functional connectivity in DMN and TPN, which could recover after the stenting. The results were not directly related to regional perfusion deficits and thus likely linked to the neuronal origins.

Artem Shatillo¹, Joanna Huttunen¹, Antti Airaksinen¹, Juha-Pekka Niskanen^1,2, and Olli Grohn^1
1Department of Neurobiology, University of Eastern Finland, Kuopio, Finland, ²Department of Applied Physics, University of Eastern Finland, Kuopio, Finland

Spreading depolarization (SD) waves are typically observed only under pathophysiological conditions. We detected spontaneously occurring SDs in 9 Sprague-Dawley rats during 1 hour long BOLD fMRI study under medetomidine sedation. Total of 17 waves were detected lasting for 193.3 ± 58.8 sec in one cortical ROI, propagating with speed of 2.93±0.6 mm/min. Observed propagation pattern and involvement of subcortical regions is atypical for ‘classical’ spreading depolarization described in literature and needs further investigations.

Shiree Heath¹, Lyndsey Nickels², Anthony Angwin³, Anna MacDonald¹, Sophia van Hees¹, Kori Johnson⁴, David Copland¹, and Katie McMahon^4
1Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia, ²Macquarie Centre for Cognitive Science, Macquarie University, Sydney, New South Wales, Australia, ³School of Health & Rehabilitation Sciences, University of Queensland, St Lucia, Queensland, Australia, ⁴Centre for Advanced Imaging, University of Queensland, St Lucia, Queensland, Australia

The current study sought to identify differences in resting state connectivity between language-related regions in unimpaired speakers and individuals with aphasia. Results show distinct patterns of connectivity for the two participant groups. Controls demonstrated greater connectivity than participants with aphasia between contralateral regions in the opposite cerebral lobe. Compared to controls, participants with aphasia showed greater connectivity in both ipsilateral and contralateral regions restricted to two specific regions in the temporal and parietal lobes. This pattern may indicate that the major disruption in connectivity for individuals with aphasia exists between homologous regions in the two cerebral hemispheres.

Jiabao He¹, Julia L Newton², and Andrew M Blamire^1
1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, ²Institue for Ageing and Health, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom

Chronic fatigue syndrome (CFS) is associated with cognitive problem and autonomic dysfunction, where the patient shows abnormal responses to autonomic challenge such as the Valsalva manoeuvre (VM). Valsalva manoeuvre provokes phased physiological response in blood pressure and cerebral blood flow, resulting in a complex cerebral response.In this work, we conducted dual echo GE fMRI to monitor the tissue water density and cerebral oxygenation level during the VM in CFS patients, and found that the BOLD signal dynamics correlated to measures of autonomic activity. Different components of cerebral reponses are related to various aspects of autonomic control.

Mohit Saxena¹, Senthil S Kumaran², Vinay Goyal¹, and Madhuri Behari^1
1Department of Neurology, All India Institute of Medical Sciences, New Delhi, Delhi, India, ²Department of N.M.R., All India Institute of Medical Sciences, New Delhi, Delhi, India

Synopsis: Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are characterized by motor dysfunction. In this fMRI study we tried to observe any difference in the BOLD activation pattern with respect to the progression of the disease, with reference to the effectiveness of the dopaminergic therapy.

Huijin Song¹, JeeHye Seo¹, Seonguk Jin¹, Hee-Kyung Kim¹, Moon-jung Hwang², Kyung Jin Suh³, and Yongmin Chang^4
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, ²GE healthcare, Seoul, Korea, ³Radiology, College of Medicine, Dongguk University, Gyungju, Korea, ⁴Medical & Biological Engineering, Diagnostic Radiology, molecular medicine, Kyungpook National University, Daegu, Korea

Fibromyalgia(FM) is disorder of unknown etiology1, characterized by chronic widespread pain and are often accompanied by symptoms of sleep disturbance, anxiety, memory problems, fatigue, and exhaustion. Previous functional imaging studies of FM mainly focused on pain by physical stimuli or functional connectivity. However, there is no emotional and cognitive effective connectivity study with FM. Therefore, the aim of this study investigates the effective connectivity using dynamic causal modeling and difference of pain network between FM patient and healthy controls in the empathy for pain stimuli. Based on our finding that the DLPFC delivers controlled pain information and intensity to insula, and insula assesses the information and perceives the pain intensity with ACC. In this study, in patients with FM, the effective connectivity between DLPFC and insula was decreased, but effective connectivity between insula and ACC was increased. Therefore, the role of DLPFC in emotional pain processing is associated with control of pain intensity and inhibitory system. If the DLPFC has a deficit or a dysfunction, patients under chronic pain perceive the more pain intensity than normal.

Samantha I. Cunningham¹, James D. Weiland², Pinglei Bao³, and Bosco S. Tjan^3,4
1Dept. of Biomedical Engineering, University of Southern California, Los Angeles, California, United States, ²Dept. of Biomedical Engineering, University of Southern California,³Neuroscience Graduate Program, University of Southern California, ⁴Dept. of Psychology, University of Southern California

FMRI was used to assess the inter-subject variability of visual cortex reorganization in individuals suffering from retinitis pigmentosa (RP), a degenerative retinal disease resulting in tunnel vision and eventual loss of sight. BOLD responses were measured as RP and sighted control groups completed two tactile discrimination tasks during successive scans in a 3T Siemens scanner. We found that vision deprivation leads to elevated activation of the visual cortex elicited with tactile stimuli, while the degree and location of activation in the primary visual cortex correlates with the degree and location of visual field loss.

Sung Suk Oh¹, Yeji Han¹, Joong Koo Kang², Eun Mi Lee², and HyunWook Park^1
1Electrical Engineering, KAIST, Daejeon, Korea, ²Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

A simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) is an effective method for epilepsy diagnosis. Using the temporal information of interictal epileptiform discharge (IED) detected in the EEG signal, the brain region related to the epilepsy can be detected with high spatial resolution in the fMRI data. To detect the IEDs more accurately, however, the measured EEG signal is analyzed after removing the ballistocardiac artifact (BA), which is induced by subject¡¯s heartbeat in a high magnetic field. In this study, three different BA removal methods, such as AAAS (advanced average artifact subtraction [1]), OBS (optimal basis set [2]), and ICA (independent component analysis [3]), were applied to the epilepsy data and their performances were evaluated in terms of preservation and restoration of the IED shapes.

Xiaodan YAN^1,2, Mariana Lazar¹, Victoria Cressman³, Leslie Prichep², Clare Henn-Haase², Irene Lee², Rachel Yehuda⁴, Thomas Neylan⁵, Daniel Sodickson¹, and Charles Marmar^2
1Radiology, New York University, New York, NY, United States, ²Department of Psychiatry, New York University, New York, NY, United States, ³Department of Psychiatry, Manhattan VA Medical Center, New York, NY, United States, ⁴Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States, ⁵Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States

Neural mechanisms of posttraumatic stress disorder (PTSD) are increasingly being investigated with neuroimaging techniques; however, previous studies have conflicting findings partly due to the differences in designed tasks and targeted behavioral variables. Using resting state fMRI (rs-fMRI), the present study examined the amplitudes of low frequency fluctuation (ALFF) as well as functional connectivity (FC) patterns associated with PTSD among 38 combat veterans (19 diagnosed as PTSD+ and 19 PTSD-, with the two groups matched on age, gender, education level and ethnicity). Compared to the PTSD- group, the PTSD+ group showed significantly decreased ALFF at the thalamus, precuneus, dorsal frontal cortex (DFC), posterior cingulate cortex (PCC), and increased ALFF at ventral anterior cingulate cortex (ACC), insula, and ventral frontal cortex (VFC). PTSD+ demonstrated primarily decreases of FC-s, particularly seeded at the thalamus, PCC, precuneus. ALFF values at DFC were negatively correlated with PTSD severity, whereas those at vACC and thalamus were negatively correlated with severity of re-experience symptom. ALFF at insula and VFC were negatively correlated with depression and dissociative symptoms respectively, and those at precuneus were positively correlated with emotion regulation capacity. These results suggest that spontaneous brain activity is associated with PTSD pathology.

Erik B Beall¹, Stephen M Rao², Micheal D Phillips¹, and Mark J Lowe^1
1Radiology, Cleveland Clinic, Cleveland, OH, United States, ²Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, United States

Traumatic Brain Injury (TBI) is a heterogeneous neurologic disorder. Past research has provided hints that blast-induced TBI represents a distinct clinical subtype, with a distinct injury mechanism causing more widespread and more homogeneous diffuse axonal injury. We compare primary motor cortex functional connectivity in blast-related and non blast-related mild to moderate TBI participants and controls with an orthopedic injury. We find that in blast-TBI participants, subcortical medial thalamic connectivity to primary motor cortex is specifically increased compared to non blast-TBI participants.

Karlene M Fraser^1,2, Ruth O'Gorman^2,3, Jozef Jarosz⁴, Gareth Barker², and Jonathan Ashmore^4
1Neuroimaging, South London & Maudsley NHS Foundation Trust, London, United Kingdom, ²Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, United Kingdom, ³Centre for MR Research, University Children's Hospital, Zurich, Switzerland, ⁴Neuroradiology, King's College Hospital, London, United Kingdom

Language fmri is becoming a standalone clinical procedure for the pre-operative assessment of neurosurgical patients, but one possible confound to the interpretation of language fMRI is that the apparent (bi)laterality of language regions depends heavily on the selected statistical threshold. This study aims to develop a simple, semi-automated post-processing method to determine language lateralisation for presurgical fMRI patients. Using this method, laterality index plots were successfully generated for all participants and were in agreement with expert neuroradiological assessment, suggesting that this method provides a simple but robust quantitative assessment of language laterality.

Aisling Spain¹, Alexandre Khrapitchev¹, Trevor Sharp², Nicola R. Sibson¹, and Chris Martin^1
1Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²Department of Pharmacology, University of Oxford, Oxford, Oxfordshire, United Kingdom

Existing pharmacological treatments for affective disorders suffer from a lack of acute efficacy. Hallucinogenic drugs are potentially useful as treatments for depression and anxiety disorders, however further investigation of their physiological effects is necessary. To understand the acute effects of hallucinogen administration in vivo, 4 male Sprague-Dawley rats were administered the serotonin 2A receptor agonist, psilocyn and underwent BOLD imaging. Increases in BOLD signal were observed in prefrontal and subcortical areas, in structures implicated in the pathophysiology of mood disorders. These results illustrate the utility of fMRI in screening drugs for acute efficacy in mood disorders.

Tynan Reid Stevens¹, Steven D Beyea¹, Ryan CN D'Arcy¹, and David B Clarke^2
1IBD-Atlantic, NRC, Halifax, Nova Scotia, Canada, ²QEII Health Science Centre, Halifax, Nova Scotia, Canada

The accuracy of presurgical fMRI is inherently related to the threshold method used to create the activation maps. We aim to demonstrate that choosing thresholds that optimize reproducibility leads to high correspondence with the gold standard, cortical stimulation (CS). Eleven patients were tested by presurgical fMRI, and observed while CS was performed in the operating room. Functional MRI maps were optimized for reliability, and the distance from each CS point to the nearest activated voxel was calculated. Reliability optimization reduced the CS-to-fMRI distance by 1-8 mm compared with traditional threshold methods.

Harald Kugel¹, Anja Stuhrmann², Victoria Beutelmann², Peter Zwanzger², Thomas Lenzen², Dominik Grotegerd², Katharina Domschke², Christa Hohoff², Patricia Ohrmann², Jochen Bauer², Christian Lindner², Christian Postert^2,3, Carsten Konrad⁴, Walter Heindel¹, Volker Arolt², Thomas Suslow⁵, and Udo Dannlowski^2
1Department of Clinical Radiology, University of Muenster, Muenster, NRW, Germany, ²Department of Psychiatry, University of Muenster, Muenster, NRW, Germany,³Department of Child and Adolescent Psychiatry, University of Muenster, Muenster, NRW, Germany, ⁴Department of Psychiatry, University of Marburg, Marburg, HE, Germany, ⁵Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, SN, Germany

Childhood maltreatment is a strong risk factor for the development of depression and posttraumatic stress disorder (PTSD) in later live. In this study, the neurobiological bases of these associations were investigated. Both, depression and PTSD have been associated with increased amygdala responsiveness to negative stimuli as well as reduced hippocampal gray matter volume, therefore we speculated that childhood maltreatment results in similar functional and structural alterations in previously maltreated but at present healthy adults. fMRI and voxel-based morphometry were applied to investigate the alterations.

Victoria L. Morgan¹, Hasan H. Sonmezturk², John C. Gore¹, and Bassel Abou-Khalil^2
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Neurology, Vanderbilt University, Nashville, TN, United States

Temporal lobe epilepsy (TLE) is a common form of epilepsy in which seizures originate from the hippocampus and adjacent structures. Resection of these structures can effectively reduce or eliminate seizures when onset is accurately lateralized. We investigated resting fMRI connectivity from each hippocampus in controls and TLE patients who were seizure free after surgery. A network between the right hippocampus and the ventral lateral nucleus of the thalamus was detected that potentially distinguishes between patients with left and right hippocampal seizure onset with high sensitivity and specificity. If validated, this technique may be practical to include in MRI presurgical examinations.

Cornelia Laule^1,2, Vlady Pavlova¹, David K.B. Li^2,3, Guojun Zhao², Piotr Kozlowski², Anthony L. Traboulsee³, and G.R. W. Moore^1,3
1Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³Medicine, University of British Columbia, Vancouver, BC, Canada

Given the potential prognostic importance of non-lesional white matter abnormalities in MS, histological studies are warranted to elucidate the pathology underlying the MRI-defined phenomena of diffusely abnormal white matter (DAWM). Post-mortem MS brain was examined with multi-echo T₂ relaxation and histological staining. DAWM showed substantial decreases in myelin water fraction (-30%) and myelin phospholipids (-29%, -24%), with much less involvement of the myelin proteins (-11% to -5%). Lesions demonstrated more severe abnormalities than DAWM, with decreases in both myelin lipids and proteins. Our findings are consistent with a primary lipid abnormality that antedates myelin protein loss in DAWM.

David Paling¹, Bhavana Solanky¹, Frank Riemer¹, Claudia AM Wheeler-Kingshott¹, Raju Kapoor¹, David H Miller¹, and Xavier Golay^2
1NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, London, United Kingdom, ²NMR Research Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, London, United Kingdom

Mapping total sodium concentration in multiple sclerosis (MS) may be a useful method of assessing pathophysiological processes including increase in intracellular sodium concentration, and increase in proportion of higher sodium concentration extracellular fluid from axonal loss. We acquired total sodium concentration maps in 10 patients with MS, and 6 controls. Increased sodium was seen in lesions as compared to the normal appearing white matter (NAWM) in MS (48.6mM vs 36.6mM, p<0.001) and in NAWM in MS as compared to controls (38.1mM vs 35.5mM, P=0.09). Further studies are underway to understand the pathophysiological significance of these findings

Mishkin Derakhshan¹, Sridar Narayanan¹, D. Louis Collins¹, and Douglas L Arnold^1
1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

We propose a novel technique for a more sensitive measurement of tissue-specific atrophy by combining the precise, longitudinal edge-displacement approach of SIENA with the tissue classification feature of SIENAx. The method is evaluated using (1) scan-rescan data and (2) simulated atrophy data and (3) is applied to a multi-centre relapsing-remitting multiple sclerosis dataset.

Tim Sinnecker¹, Jens Wuerfel^2,3, Thoralf Niendorf⁴, Friedemann Paul^2,5, Ilka Kleffner⁶, and Jan Dörr^2,5
1NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Berlin, Germany, ²NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany, ³Institute of Neuroradiology, University of Luebeck, Luebeck, Germany, ⁴Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Germany, ⁵Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany, ⁶Department of Neurology, University of Münster, Münster, Germany

Clinical and paraclinical findings including MRI findings at 1.5 T MRI in Susac syndrome often enough overlap with respective findings in MS. In fact, many patients with Susac syndrome are misdiagnosed as having MS. Realizing the brilliant signal to noise ratio at 7 T, we here studied 4 patients affected with Susac syndrome, and report substantial differences in both deep white matter and corpus callosum lesion morphology between Susac syndrome and MS. Our data i) suggest that lesion morphology at 7T supports differentiation between Susac syndrome and MS and ii) provide new insights into the pathophysiological mechanism underlying Susac syndrome.

David Paling¹, Esben T Petersen², Daniel J Tozer¹, Claudia AM Wheeler-Kingshott¹, Raju Kapoor¹, David H Miller¹, and Xavier Golay^3
1NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, London, United Kingdom, ²University Medical Center, Utrecht, Utrecht, Netherlands, ³NMR Research Unit, Department of Brain Repair and Rehabiliation, UCL Institute of Neurology, London, London, United Kingdom

Alteration in cerebral blood flow (CBF) has been noted in MS, however whether this represents change in metabolic demand, or dysregulation of perfusion control mechanisms is not established. We used the QUASAR arterial spin labelling sequence which simultaneously quantifies CBF and arterial transit time (ATT), the time taken for labelled arterial blood to transit to the capillaries, in patients with relapsing remitting MS and healthy controls. Increase in white matter ATT (1.1 vs 0.94s, P=0.05) and CBF (20.4 vs 17.1 mls min-1, p=0.02), and increase in grey matter ATT (0.99 vs 0.85s, p=0.05) was seen in MS. These findings suggest alteration in perfusion control in MS.

Olivier E. Mougin¹, Niraj Mistry², Penny A Gowland¹, Nikos Evangelou², and Klaus Schmierer^3
1Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Select, United Kingdom, ²Institute of Neuroscience, Nottingham, Select, United Kingdom, ³Barts and The London School of Medicine & Dentistry, Blizard Institute, Centre for Neuroscience & Trauma (Neuroimmunology Group), London, United Kingdom

To explore their potential to detect cortical grey matter pathology we acquired T2 weighted (T2w), T2*w, double inversion recovery, phase-sensitive inversion recovery, and magnetization transfer ratio using fixed post mortem MS brain. Voxels of 0.35mm isotropic gave a clear delineation of the grey matter, both non-lesional and lesional. Our results suggest T2w and T2*w MRI are currently the best techniques to detect cortical grey matter lesions in post mortem MS brain.

Samuel Groeschel^1,2, Christine i Dali³, Philipp Clas², Christiane Kehrer¹, Marko Wilke^1,2, and Ingeborg Krägeloh-Mann^1
1Department of Pediatric Neurology & Developmental Medicine, University Children's Hospital, Tuebingen, Germany, ²Experimental Pediatric Neuroimaging, University Children's Hospital, Tuebingen, Germany, ³Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark

Metachromatic Leukodystrophy (MLD) is a metabolic disorder leading to demyelination and neurological deterioration. We assessed cerebral gray and white matter volume as well as the volume of demyelination in relation to disease course, using a multispectral MRI segmentation approach (T1w and T2w). Eighteen patients with late-infantile MLD and 48 typically developing children of the same age range (20-59months) were analyzed. Interestingly, in MLD patients GM volume was found to be reduced already early during disease course, when their WM volume did not differ. Demyelination load increased with disease duration and motor deterioration. This may serve as reference for therapeutic intervention.

Eloy Roura¹, Torben Schneider², Pankaj Daga³, Marc Modat³, Nils Muhlert², Jordi Freixenet¹, Declan Chard², Sébastien Ourselin³, Xavier Lladó¹, and Claudia A M Wheeler-Kingshott^2
1Computer Vision and Robotics Group, Department of Computer Architecture, University of Girona, Girona, Spain, ²NMR Research unit. Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, United Kingdom, ³Centre for Medical Image Computing, Department of Medical Physics and Bioengineering, University College London, London, United Kingdom

In this work, we tested the performance of 4D multi-channel registration of T1-weighted (T1w) scans and diffusion tensor (DT) data to standard space in Multiple Sclerosis and healthy subjects. The Montreal Neurological Institute (MNI) template was chosen as target. We compared results with single-modality registration (3D) to their corresponding template. For healthy subjects the 4D multi-channel approach performed as well as the 3D approach when co-registering T1w and DT images to MNI atlas space independently. For patients the multi-channel approach improved the co-registration in the boundaries of the ventricles and also in the cortex compared to the 3D approach.

B. LIU¹, X. LIU², W. TIAN³, T. Zhu⁴, S. Ekholm⁵, and J. ZHONG^4
1Electrical and Computer Engineering, University of Rochester, Rochester, NY, United States, ²Department of Radiology, University of Rochester, United States, ³Department of Radiology, University of Rochester, Rochester, United States, ⁴Imaging Sciences, University of Rochester, Rochester, NY, United States, ⁵Department of Radiology, University of Rochester

It is of significant clinical importance to differentiate between Tumefactive demyelinating lesions (TDLs)and high-grade gliomas(HGGs) to avoid surgical biopsy. However, this goal is difficult to achieve by conventional MR imaging alone. The objective of our study is to determine retrospectively whether quantitative histogram analysis of FA and MD values can be helpful in distinguishing between TDLs and HGGs. We compare the FA value and MD value for both enhanced Tumefactive demyelinating lesions(TDLs) and enhanced high grade glioma(HGGs) with the matched location. Results showed that TDLs and HGGs could be differentiated by using the histogram method.

Anders Tisell^1,2, Johan Mellergård^3,4, Olof Dahlqvist Leinhard^1,2, Charlotte Dahle⁵, Jan Ernerudh⁶, Magnus Vrethem⁷, Anne Marie Landtblom^3,4, and Peter Lundberg^2,8
1Division of Radiological Sciences, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden, ²Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, ³Neurology, Department of Clinical and Experimental Medicine, Division of Neuroscience, Linköping University, Linköping, Sweden, ⁴Neurology Clinic, UHL, County Council of Östergötland, Linköping, Sweden, ⁵Clinical Immunology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, ⁶Clinical Immunology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden, ⁷Neurology and Clinical Neurophsiology, Department of Clincal and Experimental Medicine, Linköping University, Linköping, Sweden, ⁸Depts of Radiation Physics, Linköping University and Radiation Physics, UHL, County Council of östergötland, Linköping, Sweden

Absolute quantitative magnetic resonance spectroscopy was used for assessing the effects of natalizumab treatment on the metabolism in normal appearing white matter of MS patients. A significant change in creatine concentrations during extended treatment (three years) was observed. As creatine is more abundant in glia cells than in neurons this change suggests a reduction of glia concentration. Although higher concentrations of myo-inositol, choline containing compounds and total glutamine+glutamate were observed in the patients compered to healthy controls, the concentrations did not change in the patients as a consequence of the therapy.

Javier González-Zabaleta¹, Norberto Malpica¹, Ana Ramos², Juan Álvarez-Linera³, and Juan Antonio Hernández-Tamames^1
1Neuroimaging lab., Center for Biomedical Technology, Universidad Politécnica de Madrid and Universidad Rey Juan Carlos, Pozuelo de Alarcón, Madrid, Spain, ²Hospital 12 de Octubre, Madrid, Spain, ³Hospital Ruber Internacional, Madrid, Spain

Cortical lesions in multiple sclerosis are characterized by simultaneous hiperintensity in FLAIR images and hypointensity in T1 images. We have developed a method for automatic lesion detection that includes tissue segmentation correction, lesion detection and quantification. We have evaluated the technique in a study on Multiple Sclerosis, including 21 controls and 15 patients. All subjects were correctly classified with our method. All the algorithms have been included in a plugin for 3D Slicer.

Marios C Yiannakas¹, Hugh Kearney¹, Olga Ciccarelli², David H Miller¹, and Claudia A.M Wheeler-Kingshott^1
1Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, ²Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom

This study proposes a pipeline from acquisition to data analysis to characterise for the first time multiple sclerosis lesions in the cervical cord from MR images acquired with different contrasts. Proton density (PDw) and T1-weighted (T1w) images are acquired. Lesions are segmented using established methodologies. Magnetisation transfer ratio (MTR) measurements of the lesions, normal appearing white-matter (NAWM) and grey-matter (NAGM) are obtained and compared with healthy controls. The mean MTR of PDw lesions is very similar to the T1w lesions but more lesional tissue is visible on the PDw images than T1w.

Katherine A Koenig¹, Erik B Beall¹, Jian Lin¹, Blessy Mathew¹, Lael Stone², Robert Bermel², Stephen Rao³, Bruce Trapp⁴, Micheal D Phillips¹, and Mark J Lowe^1
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ²Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ³Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ⁴Neurosciences, Cleveland Clinic Foundation, Cleveland, OH, United States

It has been shown that functional connectivity MRI (fcMRI) from the anterior cingulate (ACC) shows correlation with cognitive function in MS. In the current study, fcMRI from the ACC for 47 MS patients and 24 healthy controls was correlated with performance on the SDMT. In patients, SDMT performance was significantly correlated with right ACC connectivity to the left caudate (r = 0.55, p=0.00006) and inversely correlated with right ACC connectivity to the left medial frontal gyrus (r = -.64, p=0.000001). Controls showed no significant correlations.

Yunyan Zhang¹, and Luanne M Metz^2
1Depts of Radiology and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada, ²Dept of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

Ten MS patients were imaged at both 1.5T and 3.0T within 48 hours using identical MRI protocols. T2-weighted MRI were corrected for non-uniformity and then were co-registered between scanners. Pixel-wise MRI texture was computed using polar Stockwell transform, from which the texture of normal appearing white matter (NAWM) regions were extracted. There was a similar pattern of regional variability in NAWM structures between field strength while texture heterogeneity was generally greater at 3.0T. No texture laterality was seen between bi-hemispheric NAWM. Texture analysis may be feasible at different scanners with different field strength by controlling for contralateral NAWM.

Janne West^1,2, Anne Aalto^2,3, J. B. M. Warntjes^2,4, Olof Dahlqvist Leinhard^1,2, Anne-Marie Landtblom^2,5, Örjan Smedby^2,6, and Peter Lundberg^1,2
1Department of Radiation Physics, Linköping University, Linköping, Sweden, ²Center for Medical Image Science and Visualization, Linköping, Sweden, ³Division of Diagnostic Radiology and Nuclear Medicine, Linköping University, Västervik, Sweden, ⁴Department of Clinical Physiology, Linköping University, Linköping, Sweden, ⁵Department of Neurology, Linköping University, Linköping, Sweden, ⁶Department of Radiology, Linköping University, Linköping, Sweden

Subtle regions of diffuse signal intensity are often seen in T2-weighted images of MS patients. These regions, not attributable to normal appearing white matter (NAWM) or WM-lesions are called dirty-appearing white matter (DAWM). Recent studies have proposed that these regions may be an important marker for disease progression. In this study it was investigated if quantitative MR could be used to identify DAWM in a group of 10 MS patients. DAWM was compared to NAWM, WM-lesions and healthy white matter in a control group. This study indicates that DAWM may be a different pathological process detectable by quantitative MRI.

Paolo Preziosa¹, Maria A. Rocca¹, Sarlota Mesaros², Elisabetta Pagani¹, Tatjana Stosic-Opincal³, Jelena Drulovic², Giancarlo Comi⁴, and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ²Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Yugoslavia, ³Clinic of Radiology, Faculty of Medicine, University of Belgrade, Belgrade, Yugoslavia,⁴Department of Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy

A voxel-wise analysis to diffusion tensor (DT) MRI tractography and T2 lesions metrics of the middle (M) and superior (S) cerebellar peduncles (CP) was applied to quantify their structural damage in multiple sclerosis (MS) patients and to assess its relationship with clinical disability. Compared to healthy controls, MS patients showed widespread diffusivity abnormalities along these tracts, which were more pronounced in clinically impaired patients. Compared to unimpaired patients, patients with overall and cerebellar clinical impairment had a higher probability of having T2 lesions in CPs. MS-related clinical impairment is due to both focal damage and diffuse white matter tract injury.

Gianna Riccitelli¹, Maria A. Rocca¹, Elisabetta Pagani¹, Vittorio Martinelli², Marta Radaelli², Andrea Falini³, Giancarlo Comi², and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ²Department of Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ³Department of Neuroradiology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy

We assessed the correlation between the regional distribution of gray matter (GM) atrophy and performances at the symbol digit modalities (SDMT) and paced auditory serial addition (PASAT) tests in 51 relapsing remitting multiple sclerosis (RRMS) patients. PASAT scores were correlated with GM atrophy in the caudate nuclei, the cerebellum and several regions mainly located in the fronto-temporo-parietal lobes, while SDMT scores were correlated with GM atrophy in the left cingulum, the parietal lobes and the bilateral cerebellum. The results suggest that deficits at SDMT and PASAT are associated to distinct patterns of regional distribution of GM atrophy in RRMS.

Wei Bian^1,2, Christopher Hess¹, Susan Chang³, Sarah Nelson^1,2, and Janine Lupo^1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Joint Graduate Program in Bioengineering, University of California San Francisco & Berkeley, San Francisco, CA, United States, ³Neurological Surgery, University of California San Francisco

The goal of this study was to compare the detection of radiation-induced cerebral microbleeds (CMBs) in glioma patients between 3T and 7T and magnitude and SWI reconstructions. Ten patients who received prior radiation therapy were scanned using T2*-weighted gradient-echo imaging at both 3T and 7T. Our results showed that although the sensitivity of CMB identification increases with field strength, the heighted susceptibility artifacts present at 7T often limited their detection. To achieve the highest detection rate of CMBs for these patients, SWI should be utilized even at 7T, and tumor location should be considered when deciding field strength.

Felix Raschke¹, and Franklyn Howe^1
1Clinical Sciences, St George's University of London, London, United Kingdom

This study takes forward recently published work using the widespread analysis tool LCModel for the analysis of 2D MRSI data of gliomas. LCModel is designed to estimate individual metabolite proportions by fitting a linear combination of metabolite spectra to an in vivo MR spectrum, but here is used to fit representations of grade II and grade IV tumour spectra and normal white matter. Colormaps and histograms are used to visualize the fitted tissue proportions and allow the clear discrimination of grade II and grade IV gliomas.

Sandy Mong¹, Ben M Ellingson², Timothy F Cloughesy³, Kim J Hyun⁴, Albert Lai³, Phioanh Leia Nghiemphu³, Leili Mirsadraei⁵, William H Yong⁵, and Whitney B Pope^4
1Radiology, UCLA, Los Angeles, CA, United States, ²UCLA, ³Neurology, UCLA, ⁴Radiology, UCLA, ⁵Pathology, UCLA

The aim of this study was to characterize the evolution and prognostic significance of persistent diffusion restriction abnormalities in patients with malignant glioma treated with bevacizumab. These patients demonstrated greater time to progression, time to survival from initiation of bevacizumab treatment and overall survival compared to matched controls. Advanced imaging correlated these diffusion signal abnormalities with hypoperfusion and decreased activity on PET scans. Histopathological examination of a resection specimen confirmed necrosis in one patient. Thus, the presence of diffusion restricted lesions in patients with malignant glioma appears to reflect treatment effect rather than hypercellular tumor in a majority of cases.

Andreas Hock¹, Fuchs Alexander¹, Peter Boesiger¹, Anke Henning¹, and Spyros S. Kollias^2
1University and ETH Zurich, Institute for Biomedical Engineering, Zurich, Switzerland, ²Institute of Neuroradiology, University Hospital of Zurich, Zurich, Switzerland

Single voxel 1H magnetic resonance spectroscopy (MRS) provides information about biochemical processes of neuronal tissue which is complementary to conventional MRI examinations and is therefore a promising tool for investigation of various spinal cord pathologies. In this work, a protocol for spinal cord MRS allowing robust and high quality spinal cord acquisitions was developed. The results show specific changes in the metabolite fingerprint of tumor patients compared to controls and patients suffering from multiple sclerosis.

Cornelia Laule^1,2, Thorarin A Bjarnason^2,3, Irene M Vavasour², Anthony L Traboulsee⁴, G.R. W. Moore^1,5, David K.B. Li^2,5, and Alex L MacKay^2,6
1Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³Diagnostic Imaging Services, Interior Health, Kelowna, BC, Canada, ⁴Medicine, University of British Columbia, Vancouver, BC, Canada, ⁵Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, ⁶Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada

Our case study attempts to better define the distribution of T₂ components in 3 different types of human brain tumours (glioblastoma, oligodendroglioma, meningioma). We used a 48-echo T₂ relaxation sequence and employed no apriori assumptions about the number of exponential components contributing to the T₂ decay. T₂ relaxation time was increased in tumour and each tumour showed a distinct T₂ distribution profile. Tumours have complex and unique compartmentalization characteristics and multi-echo T₂relaxation may be useful in evaluating different classes of brain tumours on the basis of their T₂ distribution profile. Further study with a larger sample size is warranted.

Alexandra Constantin¹, Llewellyn Jalbert¹, Adam Elkhaled², Rupa Parvataneni², Annette Molinaro², Joanna Phillips², Soonmee Cha², Susan M. Chang², and Sarah J. Nelson^2
1University of California, Berkeley, Berkeley, CA, United States, ²University of California, San Francisco

A multivariate diagnostic model was built to estimate the probability that a recurrent low grade glioma had progressed to a higher grade based on in vivo MR imaging parameters. The model was able to discriminate between recurrent low grade gliomas that upgraded versus those that remained grade 2 with 93% cross-validation accuracy and 84% bootstrapping accuracy, based on the 75th percentile normalized choline height, the 25th percentile recovery to baseline of the perfusion susceptibility curve, the 75th percentile ratio of choline to n-acetylaspartate height, and the maximum choline height inside the T2 lesion.

Guy Umberto Poloni¹, Enrico Marchioni², Giovanni Magenes³, and Gloria Castellazzi^4
1Neuroradiology, Fondazione "Istituto Neurologico Casimiro Mondino" IRCCS, Pavia, PV, Italy, ²Neurology, Fondazione "Istituto Neurologico Casimiro Mondino" IRCCS, Pavia, PV, Italy, ³Bioengineering Department, Universita' degli Studi di Pavia, Pavia, 27100, Italy, ⁴Bioengineering Department, Universita' degli Studi di Pavia, Pavia, PV, Italy

DSC-MRI represents the widespread approach in neuroradiology for the PWI of cerebral tumors, limited in its efficacy by the breakdown of the BBB associated to high grade cerebral tumors. A multi-parametric approach was adopted to overcome technical limitations of the technique on 30 consecutive untreated patients affected by glioma of grades ranging from II to IV. A voxel-wise analysis of the perfusion T2* relaxivity curves, adopting a higher number of parameters than standard and an increasing level of sophistication of the pre-analysis, was performed demonstrating an improved sensitivity to cerebral hemodynamic alterations, particularly in regions where BBB injury occurs.

Benjamin Lemasson¹, Thomas Chenevert¹, Theodore Lawrence², Christina Tsien², Pia Sundgren³, Charles Meyer^1,4, Larry Junck⁵, Jennifer Boes¹, Jean-Christophe Brisset¹, Stefanie Galbán², Timothy Johnson⁶, Alnawaz Rehemtulla¹, Brian Ross¹, and Craig Galbán^1
1Radiology, University of Michigan, Ann Arbor, Michigan, United States, ²Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States, ³Radiology, University of Michigan, Ann arbor, Michigan, United States, ⁴Biomedical, University of Michigan, Ann Arbor, Michigan, United States, ⁵Neurology, University of Michigan, Ann Arbor, Michigan, United States, ⁶Biostatistics, University of Michigan, Ann Arbor, Michigan, United States

The purpose was to evaluate the diagnostic performance of MRI based T1 and rCBV maps analyzed using a new multi-parametric response map (mPRM) base on a voxel-based analysis for early chemoradiation response prediction in patients diagnosed with high-grade gliomas. The percentage change, PRM and mPRM techniques using T1 and rCBVmap were used to assessed tumor response 1 and 3 weeks mid-treatment of 23 patients bearing glioma. mPRM_T1+/rCBV- significantly identified patients resistant irrespective of tumor volume delineation and the time point mid-treatment used. This new approach could become a powerful tool to analyze multiparametric and/or multimodal data.

Changho Choi¹, Sandeep Ganji¹, Abhishek Banerjee¹, Ivan Dimitrov^1,2, Ralph DeBerardinis¹, Craig Malloy¹, Bruce Mickey¹, Robert Bachoo¹, and Elizabeth Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Philips Medical Systems

We report noninvasive measurement of an oncometabolite, 2-hydroxuglutarate, in gliomas by TE-optimized 1H-MRS at 3T in vivo. The PRESS TE was optimized, with numerical and phantom analyses, as 97 ms for maximizing the 2HG multiplet at 2.25 ppm. This method was applied in 19 glioma patients, together with short-TE PRESS (35 ms). 2HG was detectable by both methods, but CRLB was smaller in the TE = 97 ms data than in the TE = 35 ms data. The TE = 97 ms method, with properly-calculated basis sets, may provide reliable detection of elevated 2HG compared to the short-TE method.

Pavlina Polaskova¹, Marco C. Pinho¹, Kyrre E. Emblem¹, Jayashree Kalpathy-Cramer¹, Dominique Jennings¹, Elizabeth Gerstner², A. Gregory Sorensen³, Alexander S.R. Guimaraes¹, and Tracy T. Batchelor^2
1A.A. Martinos Center for Biomedical Imaging / Massachusetts General Hospital, Charlestown, Massachusetts, United States, ²Massachusetts General Hospital Cancer Center / Harvard Medical School, Boston, Massachusetts, ³Radiology, Harvard Medical School

Serial graded functional diffusion maps (fDM) provide a new insight into a glioblastoma patient’s response to therapy. It is challenging to choose one early time-point that would accurately predict the response to therapy, because the timing of significant changes (anti-vascular effect vs anti-tumor effect) is strongly dependent on the type of therapy. By looking at multiple time-points, our longitudinal assessment allows us to show early trends rather than one-time imaging changes. We found that continuous relative decrease in ADC at early time-points as shown by longitudinal FDM is associated with shorter survival.

H-M. Baek¹, I. Marin-Valencia¹, T. Mashimo¹, Z. Zhao¹, R. DeBerardinis¹, R. Bachoo¹, C. Malloy^1,2, and E. Meher^1
1UT Southwestern Medical Center, Dallas, Texas, United States, ²VA North Texas Health Care System

This study represents, to our knowledge, the first in vitro measurements of absolute quantification of 2HG levels in IDH1/2 mutated tumors using high resolution 1H-NMR spectroscopy. The levels of 2HG in this work had a range of 0.55 - 3.51 mol/g from seven glioma samples with IDH1/2 mutation (e.g., 3 WHO grade II and 4 WHO grade III). In addition, Glu levels were found to be lower in IDH1/2 mutant tumors compared to IDH1/2 wild type tumors (P < 0.0001). This result may reflect that IDH mutations cause a decrease in Glu and/or -ketoglutarate production and an increase in 2HG.

Peter S LaViolette¹, Alex D Cohen², and Kathleen M Schmainda^1,2
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

This study measures the difference between the two separate contrast agent boluses in patients with high-grade glioma using regions of interest (ROIs) defined by a novel unbiased independent component analysis (ICA) approach.

Matthew Grech-Sollars¹, Dawn E Saunders², Kim P Phipps³, Jonathan D Clayden¹, and Chris A Clark^1
1Imaging and Biophysics Unit, UCL Institute of Child Health, London, London, United Kingdom, ²Department of Radiology, Great Ormond Street Hospital for Children, London, London, United Kingdom, ³Department of Neuro-oncology, Great Ormond Street Hospital for Children, London, London, United Kingdom

Apparent Diffusion Coefficient (ADC) measures have been shown to be related to tumour cellularity. We measured the gradient change in ADC values from the oedema into the tumour core (ATCT) in 58 children with embryonal brain tumours and correlated this with survival. More negative values of ATCT were found to be related to a lower survival probability. ATCT was shown to be a sensitive biomarker that correlated with survival in childhood embryonal brain tumours.

Peter S. LaViolette¹, Melissa A Prah¹, Mona Al-Gizawiy¹, Elizabeth J Cochran², Scott D. Rand³, Jennifer Connelly⁴, Mark G. Malkin⁵, Wade M Mueller⁶, and Kathleen M Schmainda^7
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Pathology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Radiology, Medical College of Wisconsin, ⁴Neurology, Medical College of Wisconsin, ⁵Neurology & Neurosurgery, Medical College of Wisconsin, ⁶Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ⁷Radiology and Biophysics, Medical College of Wisconsin

The aim of this study was to examine areas of overlapping dark ADC and bright rCBV in a human case of high grade glioma and compare to ex-vivo tissue acquired following death in this case report.

Vanessa H. Clark¹, Michel Bilello¹, Priyanka Bhatt¹, Xiao Da¹, Elias Melhem¹, Arastoo Vossough¹, Ron Wolf¹, Christos Davatzikos¹, and Ragini Verma^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

We aim to provide a spatial map of predicted tumor recurrence in subjects with glioblastoma which can be used to guide treatment towards improving quality of life and survival. Using 14 subjects and 9 imaging modalities, we use support vector machine classification to generate a probability map representing tissue with imaging characteristics similar to recurring/non-recurring tissues. With average 97% specificity, 27% sensitivity, and 0.79 AUC, these probability maps show potential for multimodal imaging and classification to predict patterns of tissues likely to recur that are not obvious to the human eye, including prediction of tumor recurrence at specific time intervals.

Parinaz Massoumzadeh¹, Hongyu An², Joshua Shimony¹, Dhanashree Rajderkar¹, Anna Carlson¹, Jon Christensen¹, Zhang Xiaodong², Daniel Marcus¹, Keith Rich³, and Tammie Benzinger^1
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States, ²Department of Radiology, University of North Carolina, School of Medicine, Chapel Hill, NC, United States, ³Neurosurgery, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States

Cerebral hypoxia can potentially impact treatment outcome and brain tumor patient survival. Preliminary results of a non-contrast MR procedure for measuring brain and brain tumoral OEF are presented and compared with the results obtain using the noninvasive 15O-PET technique. Although good correlation between OEF-MR and OEF-PET is obtained, and both method show abnormality in tumor area, some discrepancy between the two methods is observed which requires further investigation.

Rakesh Kumar Gupta¹, Rishi Awasthi¹, Prativa Sahoo², Bhaswati Roy¹, Sanjay Behari³, Bal Kishan Ojha⁴, Nuzhat Husain^5,6, and Ram KS Rathore^2
1Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India, ²Mathematics & Statistics, Indian Institute of Technology, Kanpur, Kanpur, Uttar Pradesh, India, ³Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India,⁴Neurosurgery, Chatrapati Sahu ji Maharaj Medical University, Lucknow, Uttar Pradesh, India, ⁵Pathology, Chatrapati Sahu ji Maharaj Medical University, Lucknow, Uttar Pradesh, India, ⁶Pathology, Ram Manohar Lohia Institute of medical Sciences, Lucknow, Uttar Pradesh, India

Forty (27 male and 13 female; mean age=43 yrs) untreated consecutive patients (25 high grades & 15 low grades on histopathology) with a postoperative diagnosis of either high or low grade glioma were imaged using 3D PC-ASL and DCE MRI. On Student’s independent t-test, all the DCE derived metrics except ve (p=0.29) were found to be significantly higher in high grade as compared to low grade glioma (p<0.001), whereas ASL derived CBF did not show any significant differences (p=0.62). We conclude that DCE-MRI proved to be superior in differentiating high grade from low grade glioma as compared to 3D PC-ASL technique.

Nuria Arias¹, Jesús Pacheco-Torres¹, and Pilar López-Larrubia^1
1Biomedical Research Institute, CSIC, Madrid, Madrid, Spain

A variety of studies have reported a direct link between low tumoral oxygenation and resistance to therapies. Several treatments have been specifically developed to modulate hypoxia in order to improve treatment success, like breathing a gas with high oxygen content during radiotherapy. It would be desirable to know a priori those tumors sensitive to this modulation. In the present work we use BOLD, sensitive to vascular oxygenation and blood flow, and TOLD contrast, sensitive to tissue oxygen level, to detect in a rat glioma model those tumors that would improve their response to radiotherapy by breathing pure oxygen during radiation.

Soren Ravn¹, Mats Holmberg², Preben Sorensen³, Jens Brondum Frokjaer¹, Thorkil Christensen¹, and Jesper Carl^4
1Radiology, Aalborg Hospital, Aalborg, Nordjylland, Denmark, ²Oncology, Aalborg Hospital, Aalborg, Nordjylland, Denmark, ³Neurosurgery, Aalborg Hospital, Aalborg, Nordjylland, Denmark, ⁴Medical Physics, Oncology, Aalborg Hospital, Aalborg, Nordjylland, Denmark

 

Manabu Kinoshita¹, Yasuyoshi Chiba¹, Akihiko Tsuboi², Naoki Kagawa¹, Jun Hatazawa³, Haruo Sugiyama⁴, Naoya Hashimoto¹, and Toshiki Yoshimine^1
1Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, ²Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, ³Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, ⁴Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Immunotherapy targeting the Wilms’ tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas with reports of encouraging results. It has become clear, however, that Gd-enhanced MRI (Gd-MRI) does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring WT1 immunotherapy. In order to meet this demand, we have performed a voxel-wise parametric response map (PRM) analysis of 11C-methionine PET (Met-PET) in WT1 immunotherapy and compared the data with the overall survival after WT1 immunotherapy initiation (OSWT1). This study describes the limited value of Gd-MRI and highlights the potential of voxel-wise PRM analysis of Met-PET for monitoring treatment response in immunotherapy for malignant gliomas.

Heiko Schmiedeskamp¹, Matus Straka¹, Thomas Christen¹, Jalal B. Andre², Seema Nagpal³, Laurence Recht³, Reena P. Thomas³, Michael E. Moseley¹, Greg Zaharchuk¹, and Roland Bammer^1
1Department of Radiology, Stanford University, Stanford, CA, United States, ²Department of Radiology, University of Washington, Seattle, WA, United States, ³Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States

Although multiecho sequences, such as Spin- And Gradient-Echo (SAGE) EPI, are inherently insensitive to T1-related CA extravasation effects, PWI processing can be biased by R2*- and R2-leakage effects. In this study, an approach used to correct for T1-effects was adjusted to account for R2*- and R2-related extravasation effects. The separation of ∆R2,e(*) from ∆R2,p(*) was achieved through pharmacokinetic modeling of CA passage through the brain. Hereby, a leakage constant ki was derived, facilitating improved assessment of brain tumors with DSC-PWI.

Sumei Wang¹, Sang Joon Kim^1,2, Matthew R Voluck¹, Ronald L Wolf¹, Donald M O’Rourke³, Harish Poptani¹, Elias R Melhem¹, and Sungheon Kim^4
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Ulsan Asan Medical Center, Seoul, Korea, ³Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁴Radiology, New York University School of Medicine, New York, NY, United States

One hundred and twenty nine glioblastomas and 74 brain metastases were included in this study. FA and MD were measured from the enhancing and immediate peritumoral region. FA values from the enhancing and immediate peritumoral regions for glioblastomas were significantly higher than those for brain metastases. Repeated split sample validation confirmed that FA and MD from the enhancing part is a robust model for the distinction between glioblastomas and brain metastases.

Danielle Van Westen¹, Filip Szczepankiewicz^2,3, Markus Nilsson², Freddy Ståhlberg², Jimmy Lätt¹, and Pia C Sundgren^3
1Center for Medical Imaging and Physiology, Skane University Hospital, Lund, Sweden, ²Department of Medical Radiation Physics, Lund University, Lund, Sweden, ³Diagnostic Radiology, Lund University, Lund, Sweden

The usefulness of DTI- and DKI-metrics along the corticospinal tract (CST) for demonstrating white matter (WM) involvement in patients with intracranial tumors was evaluated by comparing estimates in patients and healthy controls. Edema, displacement, and infiltration of the CST significantly affected the metrics along the CST in the vicinity of intracranial tumor in individual patients. However, findings were complex and a larger material is required to assess the sensitivity of DTI- and DKI-metrics and possibly redefine the criteria for the each type of WM involvement; patterns described for visual assessment did not fully account for WM involvement.

Gerard Thompson¹, Sha Zhao¹, Goeff JM Parker¹, and Alan Jackson^1
1University of Manchester, Manchester, United Kingdom

Quantitative magnetization transfer (qMT) has been used to study white matter diseases. qMT bound fraction (f) is considered to be a proxy of WM myelination. Since glial tumors arise in and invade white matter, changes in f may represent both affected white matter, and diagnostic information about the solid tumor component. Here we demonstrate that while f is not specific at distinguishing glioma grade or subtype, it is sensitive for the detection of solid tumor, and tumor and age-related white matter change in vivo. We also demonstrate that f can be derived accurately without the need for B1 correction at 3T.

Bradford A Moffat¹, Liubinas Simon², Katherine Drummond², Andrew Morokoff², Terrence O'Brien³, Chris Kokkinos⁴, and Patricia M Desmond^1
1Radiology, University of Melbourne, Parkville, Victoria, Australia, ²Surgery, University of Melbourne, Parkville, Victoria, Australia, ³Neurology, University of Melbourne, Parkville, Victoria, Australia, ⁴Radiology, Royal Melbourne Hospital, Parkville, Victoria, Australia

Glutamate concentration in human brain tumours has been quantified from 2D CSI PRESS imaging. We present HPLC validation of this technique. A High Correlation with HPLC data suggests 2D CSI is an excellent biomarker of in vivo Glutamate concentrations.

Rong Wang¹, Jiaqi Ma¹, Bolang Yu¹, Ed X. Wu², and Jian Yang^1
1Department of Radiology, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China, ²Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China

Although brain tumor stem cells (BTSCs) are demonstrated in glioma, the origin of BTSCs remains controversial. Neural stem cells (NSCs) reside in subventricular zone (SVZ) which is the largest neurogenic region in adult brain. So SVZ is considered to be the most likely source of BTSCs. This retrospective study showed that gliomas exhibited spatial proximity to SVZ when compared to metastatic tumors, implicating and supporting the possibility that the genesis of gliomas and brain tumor stem cells may originate from the mutational NSCs in SVZ.

B. J. Mulligan¹, I. S. Grunfeld¹, L. C. Baxter¹, J. M. Eschbacher², A. C. Dueck³, S. Liu¹, K. A. Smith⁴, S. W. Coons², J. E. Heiserman⁵, J. P. Karis⁵, J. Debbins¹, P. Nakaji⁴, and L. S. Hu^1,6
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, Arizona, United States, ²Neuropathology, Barrow Neurological Institute, ³Biostatistics, Mayo Clinic Arizona,⁴Neurosurgery, Barrow Neurological Institute, ⁵Neuroradiology, Barrow Neurological Institute, ⁶Radiology, Mayo Clinic Arizona

Increasing the likelihood of collecting tumor-rich samples during surgery would greatly help the diagnosis and management of high grade gliomas (HGG). We examined the utility of using Perfusion MRI (pMRI) to guide stereotactic biopsy in cases of recurrent tumor. A pMRI Fractional Tumor Burden (pMRI-FTB) was calculated from the relative Cerebral Blood Volume to differentiate between post-treatment radiation effect (PTRE) and HGG recurrence. pMRI-FTB showed strong correlation with the biopsy-derived histologic tumor fraction (r = 0.90), indicating that this may be a useful method for guiding surgical biopsies.

Erik S Poulsen¹, Leif Ostergaard¹, Patricia M Desmond², C Kokkinos², Kate Drummond², and Brad Moffat^2
1Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark, ²Department of Radiology, University of Melbourne, Melbourne, Victoria, Australia

Dynamic 3D contrast-enhanced imaging using a k-space sharing technique (TWIST) permits whole brain coverage with high special resolution at a temporal resolution of ~1 sec. Hence, simultaneous permeability and perfusion imaging of brain tumours can be acquired without the drawbacks of routinely used dynamic susceptibility contrast (DSC) technique. Permeability and perfusion measurements could serve as biomarkes of tumour grade and patient outcome. If validated, tumour vasculature pheno-typying using these biomarkers could be applied to any solid tumour. Quantitative data from ~20 brain tumour patients will be presented in comparison with DSC.

Sumei Wang¹, Ronald L Wolf¹, Edward B Lee², Harish Poptani¹, Elias R Melhem¹, John YK Lee³, and Sungheon Kim^4
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States,³Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁴Radiology, New York University School of Medicine, New York, NY, United States

The purpose of this study is to determine whether permeability and rCBV measurements can help in determining the histologic grade and subtypes of meningiomas. Thirty-one meningiomas underwent DSC studies. All the perfusion parameters including corrected rCBV, uncorrected rCBV, Ktrans, Ve and Vp were measured from the enhancing part of the tumor. Our result showed that corrected rCBV is helpful in differentiating atypical from typical meningiomas, whereas Ktrans and Ve measurements are useful in distinguishing different subtypes of meningiomas.

Michael Wahl¹, Christopher Kazu Williams², Janine Lupo², Susan Chang³, Daphne Haas-Kogan¹, and Sarah Nelson^2,4
1Radiation Oncology, University of California, San Francisco, San Francisco, CA, United States, ²Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ³Neurosurgery, University of California, San Francisco, San Francisco, CA, United States, ⁴Bioengineering and Theraputic Sciences, University of California, San Francisco, San Francisco, CA, United States

Everolimus is an inhibitor of mTOR, a molecule in a signaling pathway activated in most low-grade gliomas and known to have angiogenic effects. In this phase II clinical trial, patients with recurrent low grade gliomas are treated with everolimus and followed with serial multimodal MRI while on treatment. We observe a significant decrease in DCE perfusion MRI parameters, including FBV (a measure of capillary density) and Kps (a measure of vascular permeability). This represents the first clinical demonstration of antiangiogenic effects of everolimus, and raises the possibility that perfusion parameters can be used as early markers of treatment response.

Rupa Parvataneni¹, Ramon Barajas¹, Annette Molinaro², Gabriela Bourne¹, Emma Essock-burns¹, Joanna Phillips³, Soonmee Cha¹, Susan Chang², and Sarah Nelson^1,4
1Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²Neurosurgery, University of California, San Francisco, California, United States, ³Pathology, University of California, San Francisco, California, United States, ⁴Bioengineering and Therapeutic Sciences, University of California, San Francisco

The purpose of this study was to obtain image guided tissue samples from regions of suspected tumor in untreated GBM patients and compare ex vivo histopathology features with in vivo imaging biomarkers in order to characterize enhancing (CE) versus non enhancing (NE) tumor. Our study showed that DSC imaging parameters were associated with more malignant histology for CE regions, while DWI parameters were associated with more malignant histology in regions of NE tumor. These results are particularly important in delineating tumor margins during the initial surgical resection and in determining the optimal therapeutic interventions during subsequent stages of the disease.

Llewellyn Jalbert¹, Adam Elkhaled², Joanna Phillips³, Rupa Parvataneni², Soonmee Cha², Susan Chang⁴, and Sarah Nelson^2,5
1Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States, ²Radiology and Biomedical Imaging, University of California, San Francisco, ³Pathology, University of California, San Francisco, ⁴Neurosurgery, University of California, San Francisco, ⁵Bioengineering and Therapeutic Sciences, University of California, San Francisco

Gliomas are heterogeneous, infiltrating tumors of the central nervous system that include astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. The prognosis for these patients can vary significantly depending on the grade of malignancy and histological characteristics, as defined by the World Health Organization (WHO). Previous studies have shown that ex vivo spectroscopy can discriminate between upgraded and non-upgraded lesions, but it there are significant limitations that remain in the assessment of malignant transformation using conventional MR imaging methods. This study has applied advanced in vivo magnetic resonance imaging and spectroscopy techniques to characterize parameters that are associated with malignant transformation.

Yaniv Gal¹, Stephen Rose², Pierrick Bourgeat³, Nicholas Dowson³, Zeike Taylor⁴, Michael Fay⁵, Paul Thomas⁵, Olivier Salvado³, and Stuart Crozier^1
1School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Queensland, Australia, ²Centre of Clinical Research, University of Queensland, Brisbane, Queensland, Australia, ³CSIRO, Brisbane, Queensland, Australia, ⁴Department of Mechanical Engineering, The University of Sheffield, Sheffield, United Kingdom, ⁵Royal Brisbane and Women’s Hospital, Brisbane, Brisbane, Queensland, Australia

A method for automatic assessment of high grade brain tumour tissue in MR images is presented. The aim of the method is to differentiate between tumour tissue and radiation injured tissue. The method is validated qualitatively on two high grade brain cancer patients and demonstrates high potential.

Vincent Lee¹, Anthony DeAngelo², Jonathan Weimer³, Frank Lieberman⁴, Denise Davis⁵, Yongxian Qian², and Fernando Emilio Boada^2
1Radiology and Bioengineering, University of Pittsburgh, Piitsburgh, PA, United States, ²Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States,³Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Neurology, University of Pittsburgh, Pittsburgh, PA, United States, ⁵Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Sodium MRI changes in response to the proliferative activity of brain tumors. In this work we demonstrate the use of 3D sodium MRI for following chemotherapy in brain tumor patients.

Andreas Deistung¹, Ferdinand Schweser¹, Sabine Heiland², Martin Bendszus², Wolfgang Wick³, Jürgen Rainer Reichenbach¹, and Alexander Radbruch^2
1Medical Physics Group, Department of Diagnostic and Interventional Radiology I, Jena University Hospital, Jena, Germany, ²Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany, ³Department of Neurooncology, University of Heidelberg Medical Center, Heidelberg, Germany

On susceptibility weighted images glioblastoma usually exhibit a large amount of intratumoral susceptibility signals (ITSS), enabling differentiation from other enhancing brain lesions. However, it is still unknown if these ITS signals correspond to calcium or blood deposits. Therefore, this contribution assesses ITSS in glioblastoma with quantitative susceptibility maps to differentiate between calcium or blood deposits. ITSS were classified as 80-100% hyperintense in 8 of 9 glioblastoma whereas only one of 9 glioblastoma was classified as 60-80% hyperintense, indicating that ITSS in glioblastoma originate from blood products. These findings may improve the understanding of the pathophysiology of glioblastoma.

Yan Li¹, Laleh Jalilian¹, Youngho Seo¹, Dave Wilson¹, Miguel Pampaloni¹, Henry Vanbrocklin¹, Michael Prados², and Sarah J Nelson^1,3
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²Department of Neurosurgery, University of California, San Francisco, California, United States, ³Department of Bioengineering and Therapeutic sciences, University of California, San Francisco, California, United States

The purpose of this study was to assess the correlation between18F-fluoromisonidazole PET (18F-FMISO-PET) parameters and those from MRI, including perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) in patients with GBM for whom progression was suspected. Three patients diagnosed with glioblastoma Multiforme (GBM) were studied at the time of suspected progression. The relationship of the PET parameters to the MRI-defined abnormalities was examined. Elevated CBV and PH values were detected in a region that corresponded with T/B>=1.1.

Matthew Grech-Sollars¹, Dawn E Saunders², Kim P Phipps³, Jonathan D Clayden¹, and Chris A Clark^1
1Imaging and Biophysics Unit, UCL Institute of Child Health, London, London, United Kingdom, ²Department of Radiology, Great Ormond Street Hospital for Children, London, London, United Kingdom, ³Department of Neuro-oncology, Great Ormond Street Hospital for Children, London, London, United Kingdom

The functional diffusion map (fDM) has been suggested as a tool for early detection of tumour treatment efficacy. Theoretically, on its own, a change in size in necrotic areas does not necessarily give an indication of whether the tumour is responding well to treatment or not. We analysed data from 11 patients with brain stem tumours and built fDM maps of the necrotic regions of the tumour from the ADC images. The fDM in necrotic areas did not appear to correlate with survival. We hypothesize that areas of necrosis can act as a confounding factor in the fDM.

Dita Wagnerova¹, Vit Herynek¹, Alberto Malucelli², Monika Dezortova¹, Josef Vymazal³, Dusan Urgosik⁴, Martin Syrucek⁵, Filip Jiru¹, Antonin Skoch^1,6, Robert Bartos², Martin Sames², and Milan Hajek^1
1Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²Department of Neurosurgery, JE Purkyne University and Masaryk Hospital, Usti nad Labem, Czech Republic, ³Department of Radiology, Na Homolce Hospital, Prague, Czech Republic, ⁴Stereotactic and radiation neurosurgery, Na Homolce Hospital, Prague, Czech Republic, ⁵Department of Pathology, Na Homolce Hospital, Prague, Czech Republic, ⁶International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic

The specific correlation patterns between metabolic values, mean diffusivity and T2 relaxation times based on multivoxel analysis were observed for low and high grade gliomas, lymphomas, recurrent lesions and tissue changes by radiation/chemotherapy which enable not only tissue differentiation (healthy tissue, edema, tumor infiltrated edema, tumor; tumor recurrence vs. radiation necrosis), but also tumor type differentiation. Combination of several MR methods can be used for quantitative description of tumors to improve the outcome from MR examination of patients.

Yaniv Gal¹, Stephen Rose², Pierrick Bourgeat³, Nicholas Dowson³, Zeike Taylor⁴, Michael Fay⁵, Paul Thomas⁵, Olivier Salvado³, and Stuart Crozier^1
1School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Queensland, Australia, ²Centre of Clinical Research, University of Queensland, Brisbane, Queensland, Australia, ³CSIRO, Brisbane, Queensland, Australia, ⁴Department of Mechanical Engineering, The University of Sheffield, Sheffield, Sheffield, United Kingdom, ⁵Royal Brisbane and Women’s Hospital, Brisbane, Brisbane, Queensland, Australia

A method for automatic classification of high grade brain tumour MRI for improved resection and therapy planning is proposed. The method is validated qualitatively and quantitatively on MRI and FDOPA PET images and is found to increase the sensitivity of contrast enhanced MRI to high grade brain tumours.

Vishal Patil¹, and Glyn Johnson^1
1Radiology, NYU School of Medicine, New York, New York, United States

DSC MRI measurements of relative cerebral blood volume, referenced to normal appearing white matter (NAWM), are frequently used in monitoring treatment response. Bevacizumab is the first FDA approved anti-angiogenic agent and has shown efficacy in glioma when used in combination with conventional cytotoxic agents. In this study we calculated NAWM CBV in three sets of patients groups; 1) never received bevacizumab, 2) received bevacizumab after initial diagnosis and 3) only after reoccurrence. Results show significant reductions in NAWM CBV after treatment with bevacizumab, suggesting that care need be exercised in the use of rCBV measurements to monitor treatment response.

Benjamin M Ellingson¹, Timothy F Cloughesy², Whitney B Pope¹, Taryar M Zaw¹, Phioanh L Nghiemphu², Kourosh M Naeini¹, Robert J Harris¹, and Albert Lai^2
1Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ²Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Studies support tumor location as playing an important role in prognosis, likely due to the genetic profile of tumor precursor cells and the stage in the development cycle that these cells transform (i.e. the glioma “cell of origin”). However, identifying such glioma “cells of origin” is still a major issue challenging the field of neuro-oncology. In the current study we have constructed “probabilistic atlases” specifying the most frequent tumor locations on MR for more than 400 patients. These atlases were stratified by different biological and interventional phenotypes to provide new insight into niche locations of specific glioma cells of origin.

Felix Raschke¹, Nigel Davies², Martin Wilson², Andrew Peet², and Franklyn Howe^1
1Clinical Sciences, St George's University of London, London, London, United Kingdom, ²Cancer Sciences, University of Birmingham, Birmingham, United Kingdom

This study takes forward recently published work using the widespread analysis tool LCModel for the direct classification of single voxel 1H MR spectra of the paediatric brain tumours Medulloblastoma (MDB), Astrocytoma (AG) and Ependymoma (EPD). LCModel is designed to estimate individual metabolite proportions by fitting a linear combination of metabolite spectra to an in vivo MR spectrum, but here is used to fit representations of complete tumour spectra. The best classification according to the highest estimated tumour proportion in a leave-one-out analysis compared well to previously published work with 100.0% and 87.7% for MDB vs. AG and MDB vs. AG vs. EPD respectively.

Ashok Panigrahy^1,2, Regina Jakacki³, Rafael Ceschin¹, Stefan Bluml^2,4, Yongxian Qian⁵, Fern Wasco¹, James Mountz⁵, Ian F. Pollack⁶, and Fernando Boada^5
1Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ²Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, CA, United States, ³Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁴Department of Biomedical Engineering, University of So uthern California, Los Angeles, CA, United States, ⁵Department of Radiology, UPMC Presbyterian Hospital, Pittsburgh, PA, United States, ⁶Department of Neurological Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States

It is possible to calculate soidum concentration within a spectrum of pediatric brain tumors. Sodium MR imaging in pediatric brain tumors may detect regional areas within diffuse astrocytoma which may behave more aggressive.

Abby Y. Ding^1,2, Qi Li^3,4, Iris Y. Zhou^1,2, Grainne M. McAlonan^3,4, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China, ³Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China, ⁴Centre for Reproduction Growth and Development, The University of Hong Kong, Hong Kong SAR, China

Fear conditioning (FC) is widely used to study the neural basis of learning and memory. The pivotal role of amygdala and hippocampus in memory formation and consolidation is well documented. In vivo DTI was employed in this study, voxel-based significant and distinct FA changes were found in amygdala and hippocampus, suggesting possible microstructural up-regulating in amygdala versus down-regulating in hippocampus 1 hour post-FC. Such changes reverted at 24 hr post-FC in various DTI indices. Our results indicated that DTI could be sensitive to probe short-term plasticity, and may provide insights for the accompanied brain plasticity network after FC

Jieun Kim¹, In-Young Choi^1,2, Yafeng Dong³, Wen-Tung Wang⁴, William Brooks¹, Carl Weiner³, and Phil Lee^1,5
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Neurology, University of Kansas Medical Center, Kansas City, KS, United States, ³Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS, United States, ⁴Center for Neuroscience and Regenerative Medicine, NIH/USUHS, Baltimore, MD, United States, ⁵Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Chronic hypoxia during the gestation period (hypoxemia) can cause the neuronal death and slow neural migration in the developmental brain. This study aims to investigate the effects of chronic fetal hypoxia on postnatal guinea pigs in the developing brain longitudinally using in vivo MRI of T2 maps, DTI and volume measurements. DTI and T2 measurements suggest delayed axonal myelination and tissue maturation during development of neonatal guinea pigs that experienced chronic fetal hypoxia.

Shiliang Huang¹, Qiang Shen¹, Fang Du¹, Yen-Yu I Shih¹, and Timothy Q Duong^1
1Reseach Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Recovery of perfusion and/or diffusion abnormalities does not necessarily indicate functional and metabolic recovery in stroke. In this study, we developed a protocol for combined diffusion, perfusion and functional MRI to investigate transient focal ischemia in rats during the acute and chronic phase. Quantitative perfusion and diffusion imaging was performed and an improved ISODATA cluster analysis was used to classify normal, ischemic core and “diffusion-perfusion mismatch” tissues. BOLD and CBF fMRI was used to evaluate the hypercapnic and forepaw-stimulation responses in different brain regions and in the forepaw somatosensory cortices up to one month post-ischemia.

Yen-Yu Ian Shih¹, Shiliang Huang¹, Fang Du¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

The present study aimed to longitudinally investigate the striatum function in two groups of stroke rats ¡V 20-min middle cerebral artery occlusion (MCAO) and 45-min MCAO. Our results demonstrated that the CBV fMRI reliably depicts striatal and cortical functions in stroke rats and 20- min MCAO showed better functional recovery. This technique has potential to longitudinally investigate the functional reorganization and evaluate treatment efficacy in the striatum of the same animal after stroke.

Chien-Hsiang Huang^1,2, Chiao-Chi V. Chen², Tiing-Yee Siow², Fu-Shan Jaw¹, and Chen Chang^2
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Vascular remodeling which restores oxygen and nutrient supply to the affected tissues improves the prognosis of stroke patient. Evaluating restorative strength of the remodeled vessels after ischemic insult provides important information to help guide the strategy of follow-up therapy. Dilatability and oxygenation ability of the vessels are the key characteristics that determine the restorative strength. This study aimed to explore the temporal changes of dilatability and oxygenation ability after transient focal cerebral ischemia in rats using BOLD MRI.

Lesley M Foley¹, Tomas Drabek², Jason Stezoski², T Kevin Hitchens^1,3, Robert S Clark^2,4, Chien Ho^1,3, and Patrick M Kochanek^2,5
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States, ²Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ³Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States, ⁴Department of Pediatrics, Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Departments of Critical Care Medicine, Pediatrics and Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Cardiopulmonary arrest is associated with high mortality and morbidity. In this study we examined if two different insults, namely ventricular fibrillation cardiac arrest (VFCA) and asphyxia cardiac arrest (ACA), result in different spatial and temporal patterns of cerebral blood flow (CBF), with the aim of tailoring therapies specifically to the type of insults sustained. The insults produced early transient hyperemia which was significant in the ACA model, followed by significant hypoperfusion particularly in the VFCA insult. While the mechanisms are yet to be determined, our data suggest that hypoperfusion may be an important therapeutic target particularly for resuscitation following VFCA.

Hsiao-Ying Wey^1,2, Ghazwan M Kroma³, Jinqi Li^2,3, M Michelle Leland⁴, Lisa Jones⁴, and Timothy Q Duong^2,3
1Department of Radiology, A. A. Martinos Center for Biomedical Imaging, MGH/Harvard Medical School, Charlestown, MA, United States, ²Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ³Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ⁴Department of Laboratory Animal Resources, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

This study describes the development of a large non-human primate (baboon) stroke model (permanent and transient stroke) and the implementation of multiparametric MRI protocols to characterize the evolution of lesion volume, the perfusion-diffusion mismatch, quantitative CBF and ADC changes, and cerebral vascular reactivity. Improved understanding of the lesion evolution and perfusion-diffusion mismatch in clinically relevant model of stroke might provide important information to better guide clinical diagnosis, test novel interventions and improve treatment time windows.

Ji-Yeon Suh¹, Woo Hyun Shim¹, Dong-Wha Kang², Xiaoying Wang³, Xiang Fan³, Jeong Kon Kim^1,2, Christian Farrar¹, and Young Ro Kim^1
1Athinoula A, Martinos Center for Biomedical Imaging, Massachusettes General Hospital, Charlestown, MA, United States, ²Asan Medical Center, University of Ulsan, Seoul, Korea, ³Neurology and Radiology, Massachusettes General Hospital, MA, United States

In this study, in order to characterize the altered vascular function in stroke brain, the relationships between the hypercanpia-induced vascular responses and the baseline vascular states are monitored using an alternating GE/SE EPI in acute permanent MCAO rats. Our results showed globally decreased cerebral responses in ipsilesional hemisphere. Interestingly, the decrease of baseline MVV in ipsilesional hemisphere was considerable, which drastic change may alter the cerebral hemodynamic properties, hence suppressing the CO2 reactivity in the entire ipsilesional hemisphere. Our results provide an important basis for understanding the impaired cerebrovascular reactivity due to occlusion of major cerebral arteries.

Mark J Bouts¹, Ivo A Tiebosch¹, Annette van der Toorn¹, Jeroen Hendrikse², and Rick M Dijkhuizen^1
1Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

In cerebral ischemic stroke, characterization of the extent and location of vessel occlusion in relation to the spatiotemporal development of ischemic lesions may lead to improved diagnosis. Therefore, we aimed to distinguish different patterns of occlusion of segments of the Circle of Willis, measured with MRA, and correlate these with acute ischemic lesions, measured with diffusion- and perfusion-weighted MRI, in a rat embolic stroke model. We found that occlusion of the proximal segment of the middle cerebral artery (MCA.M1), was most strongly associated with development of a large acute ischemic lesion in cortical and subcortical tissue, whereas occlusion of the internal carotid artery in conjuction with incomplete occlusion of the MCA reduced acute lesion growth.

Duncan Jack Hodkinson¹, John Gigg², Diana Cash³, Steve CR Williams³, John-Francis William Deakin⁴, and Steve R Williams^1
1Imaging Sciences Research Group, University of Manchester, Manchester, United Kingdom, ²Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom,³Institute of Psychiatry, King's College London, London, United Kingdom, ⁴Neuroscience & Psychiatry Unit, University of Manchester, Manchester, United Kingdom

Minocycline is a safe, routinely prescribed broad-spectrum antibiotic effective against neuro-inflammation and oxidative cell stress. These actions may mediate the beneficial effects of minocycline on negative symptoms in schizophrenia. Here, we show that pre-administration of minocycline induces widespread attenuation of the ketamine-induced phMRI response. However, minocycline also inhibited BOLD responses to electrical hindpaw stimulation, though cortical local field potential changes were still present. These findings are consistent with pharmacologically-induced disruption of neurovascular coupling. These results are interpreted in the context of previous findings linking minocycline to modulation of aberrant glutamate NMDA function.

Takashi Watanabe¹, Jens Frahm¹, and Thomas Michaelis^1
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany

This work demonstrates the use of MnCl₂ and Gd-DTPA to improve the white/gray matter contrast in magnetization-transfer MRI (3D FLASH) of the brain and spinal cord of living mice at 9.4 T. A systemic Mn²⁺ administration followed by an intraventricular Gd-DTPA administration increased the white/gray matter CNR by 136%. At 60 m isotropic resolution, myelinated fibers and layers were delineated with the contrast agents, even within the gray matter. The contrast enhancement can be explained by its lower/higher concentration of the contrast agents in the white/gray matter, with the extracellular space in the white/gray matter estimated to be 15%/27%, respectively.

Agatha Lyczek^1,2, Miroslaw Janowski^1,2, Jinyuan Zhou^1,3, Jiadi Xu^1,3, Peter PC van Zijl^1,3, Jeff WM Bulte^1,2, and Piotr Walczak^1,2
1Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, ³F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

It is believed that leukocyte trafficking into the central nervous system contributes substantially to secondary brain damage, exacerbating the follow-up effects of ischemia. Characterizing stroke lesions in immunocompetent (balb/c) versus immunodeficient (rag2-/-) mice may provide an important insight into neuroinflammation in stroke. We characterized, with MRI, the evolution of ouabain-induced stroke in balb/c and rag2-/- mice, and we demonstrate that, although all mice developed similar acute lesions, immunodeficient mice dramatically improved by day five, while continued deterioration was observed in immunocompetent animals.

Kevin C. Chan^1,2, Shu-juan Fan^1,3, Iris Y. Zhou^1,3, and Ed X. Wu^1,3
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong, China, ²Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ³Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China

Chromium (Cr) has been used histologically to stabilize lipid fractions in the retina, and is suggested to enhance oxidizable lipids in brain MRI. This study explored the feasibility, sensitivity and specificity of in vivo chromium-enhanced MRI (CrMRI) of retinal lipids, by determining its spatiotemporal profiles and toxic effect after intravitreal Cr(VI) injection to normal and injured adult rats. One day after 3£gL Cr(VI) administration at 1mM to 100mM, the normal retina exhibited a dose-dependent increase in T1-weighted hyperintensity until 50mM. Time-dependently, significant T1-weighted hyperintensity persisted up to 2 weeks after 10mM Cr(VI) administration. While CrMRI demonstrated reduced Cr enhancement in hypoxic-ischemic-injured retina, 3D-CrMRI of ex vivo normal eyes at isotropic 50£gm resolution showed at least 5 alternating bands across retinal layers, with the outermost layer being the brightest. This agreed with histology indicating alternating lipid contents with the highest level in the photoreceptor layer of the outer retina. While Cr(VI) reduction may induce oxidative stress and depolymerize microtubules, manganese-enhanced MRI after CrMRI showed a dose-dependent effect of Cr toxicity on Mn uptake and axonal transport along the visual pathway. These results potentiated longitudinal CrMRI studies on retinal lipid metabolism upon further optimization of Cr doses with visual cell viability.

Julie Magat¹, Caroline Vandeputte², Uwe Himmelreich², Bénédicte F Jordan¹, and Bernard Gallez^1
1Biomedical Magnetic Resonance Group, Université Catholique de Louvain, Brussels, Belgium, ²Biomedical Nuclear - Magnetic - Resonance Unit, Katholieke Universiteit Leuven, Leuven, Belgium

Imaging brain tissue oxygenation shortly after an acute ischemic stroke may help to aid in the selection of patients who may still benefit from thrombolytic treatment beyond conventional time-based guidelines. There is a critical need for methods able to monitor dynamically and noninvasively brain oxygenation. The aim of the current work was to implement the MOBILE technique, a method developed to map variations in oxygenation based on the changes in the relaxation properties of the tissue lipids by exploiting the higher solubility property of oxygen in lipids than in water (5), in a mouse stroke model.

Fang Du¹, Qiang Shen¹, Shiliang Huang¹, and Timothy Q Duong^1
1Reseach Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Mismatch of diffusion/perfusion by MRI has been used as an estimate of the ischemic penumbra, but there are large parts of the mismatch region appear not to at risk and it was also reported that some of the apparent diffusion coefficient reduction area can be salvaged by early reperfusion. We hypothesis that T2*-weighted signal change following oxygen challenge could be used as an improved biomarker of penumbra. We tested this hypothesis on transient (45 mins) focal ischemic rats.

Hongxia Lei^1,2, Frederic Preitner³, Bernard Thorens³, and Rolf Gruetter^1,3
1Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, ²University of Geneva, Geneva, Geneva, Switzerland, ³University of Lausanne, Lausanne, Vaud, Switzerland

Glucose transporter isoform 2 (GLUT2), one of GLUTs, has been suggested to involve in the glucose sensor mechanism not only in pancreas but also in brain. How GLUT2 affect brain metabolism remained not well understood. We hypothesize that lacking GLUT2 in brain could interfere brain glucose sensor mechanism thus attenuate brain metabolism. In present study, we explored both localized 1H MRS and CASL on GLUT2-/- mice and their countertypes at 9.4T. While at euglyemia and under isoflurane anesthesia, metabolic alterations were consistently observed in hippocampus of GLUT2-/- mice, such as elevated blood flow and selected metabolites including taurine, myo-inositol and total creatine. The observations suggested that GLUT2 indeed affect brain tissue, i.e. hippocampus, substantially.

Jia Zhong^1,2, Masashi Sakaki³, Hideho Okada^3,4, and Eric T Ahrens^1,2
1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States, ²The Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, ³Brain Tumor Program, Cancer Institute, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Immunotherapy using live cells is opening up new avenues for brain tumor treatment with minimal damage to healthy tissue. Noninvasive biomarkers of therapeutic efficacy is of great importance for the evaluation of emerging immunotherapies. In this study, we report the use of intracellular perfluorocarbon (PFC) labeling of glioma cells, combined with 19F T1 measurements, to assay glioma oximetry. We show that glioma oxygen level responds sensitively to the influx of therapeutic cytotoxic CD8+ T cells into mouse glioma. We also show that intracellular oximetry can detect the presence of sparse CD8+ T cell numbers, even in the absence of significant tumor shrinkage.

Naranamangalam Raghunathan Jagannathan¹, Krithika Balasubramanian¹, Uma Sharma¹, and Senthil S Kumaran^1
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India

The objective was to characterize and quantitate metabolites in demyelinated rat brain tissues and compare it with the normal tissues of control rats by in-vitro 1H-MRS. Overall 28 metabolites were unambiguously assigned. The concentration of N-acetyl aspartate (NAA) reduced while that of alanine (Ala) and taurine (Tau) increased in demyelinated tissues. Decreased NAA is attributed to breakdown of myelin and increased Tau is related to decreased signal transmission across the demyelinated neurons. Ala serves as a nitrogen carrier between glutamatergic neurons and surrounding astrocytes and its increase may be attributed to damage to these neurons leading to its accumulation.

Ai-Ling Lin¹, Peter T Fox¹, Holly Van Remmen², Andrew Bresnen¹, Anuradha Soundararajan¹, Eric Muir¹, Arlan G Richardson², and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Anotnio, San Antonio, TX, United States, ²Barshop Institute for Logevity and Aging Studies, University of Texas Health Science Center at San Anotnio, San Antonio, TX, United States

Reduced mitochondrial function has been recently found to be associated with increased lifespan in various organisms. Herein we measured the effects on metabolism in mouse brain of decreased mitochondrial function induced by a genetic manipulation (Surf1 knock out) which reduced levels of cytochrome c oxidase (COX). Using non-invasive, in vivo neuroimaging, we quantified metabolic function in Surf1 KO mice and WT controls. Significant increases in glucose uptake and lactate concentration (an index of glycolysis) were found in both young (6-7 months old) and aged (17-18 months old) adult Surf1 KO mice compared to age-matched WT controls. Concentrations of essential neuronal metabolites (e.g., NAA and glutamate/glutamine) and energy substrates (i.e., ATP) remained unchanged in Surf1 KO mice during aging but decreased significantly in WT controls. Our results suggest that decreased mitochondrial function can mitigate age-related declines in brain physiology and may provide an explanation for the extended lifespan of Surf1 KO mice.

Cristina Cudalbu¹, Valérie McLin², Olivier Braissant³, Nicolas Kunz^1,4, Yohan van de Looij^1,4, and Rolf Gruetter^1,5
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland, ²Département de l'Enfant et de l'Adolescent, Unité de Gastroentérologie, Hépatologie et Nutrition, Hôpitaux Universitaires de Genève (HUG), Geneva, ³Laboratoire de Chimie Clinique, Département de Pathologie et de Médecine de Laboratoire, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland, ⁴Division of Child Growth & Development, University of Geneva, Geneva, Switzerland, ⁵Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

Chronic liver disease (CLD) is characterized by an array of cognitive and fine motor deficits labeled as hepatic encephalopathy. No in vivo longitudinal Spectroscopic Imaging (1H-SI) or Diffusion Tensor Imaging (DTI) studies were performed in CLD animal models. The aim was to analyze the in vivo alterations in brain osmolytes and brain edema using longitudinal 1H SI and DTI methods at 9.4T. Our preliminary data show that in CLD before the appearance of severe neurological signs, the osmotic imbalance created by the continuous increase of Gln can be compensated by a continuous decrease of other osmolytes with minimal brain edema.

Norbert W. Lutz¹, Carla Fernandez², Jean-François Pélissier², Patrick J. Cozzone¹, and Evelyne Béraud^2
1CRMBM UMR CNRS 6612, Université Aix-Marseille, Faculté de Médecine, Marseille, France, ²CRO2 UMR INSERM 911, Université Aix-Marseille, Faculté de Médecine, Marseille, France

This metabolomic study contributes to our understanding of the mechanisms involved in the induction of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Effects of EAE-inducing agents, Complete Freund's Adjuvant (CFA) and Spinal-Cord Homogenate (SC-H), were determined by ¹H NMR spectroscopy of rat brain extracts. In both CFA and CFA/SC-H-treated groups the phospholipid content, in particular ethanolamine-containing phospholipids, and glycolysis were increased. Among the osmolytes studied, NAA and taurine were decreased, but not the astrocyte marker, myo-inositol. Histological results suggest the possibility of neuron shrinkage and mild gliosis underlying these metabolic changes, but stress effects are also to be considered.

N. Agarwal¹, L. D'Silva¹, E. M. Kan², S. K. Verma¹, S. Seramani¹, K. C. Ng², E. A. Ling³, J. Lu², and S. Sendhil Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore, ²Combat Care Laboratory, Defence Medical and Environmental Research Institute, DSO National Lab, Singapore, Singapore, ³Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Traumatic Brain Injury (TBI) can cause lasting neuropsychological damage and impair the day-to-day functionality for survivors. In this study, we have investigated the changes in brain morphology, cognitive function and metabolism affected by fluid percussion injury in rodent models with Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (MRS). The current study demonstrates good correlation in results obtained by DTI and 1H MRS to track white matter changes in the traumatic brain injury model in rodents. This suggests that regional cerebral changes in ADC and NAA/Cr values may serve as a possible diagnostic marker for cognitive performance after TBI.

Dong-Cheol Woo¹, Goo-Young Kim², Hyun-Joo Kim³, Eunjung Bang³, Hyang-Shuk Rhim², Sang-Young Kim², Do-Wan Lee², Robert Lenkinski¹, and Bo-Young Choe^2
1Department of Radiology, UT southwestern medical center, Dallas, Tx, United States, ²The Catholic university of korea, ³Korea Basic Science Institute

Here we investigate the brain metabolism of zebrafish to acute alcohol treatment by using the nuclear magnetic resonance spectroscopy and the whole brain extraction. Our results show that glutamate significantly decreased in a quasi-linear dose dependent manner, scyllo-inositol showed a smaller apparent increase only in the highest acute dose group and myo-inositol showed a significant decrease. We discuss the methodological novelty of our work and theorize about the implications of the brain neurochemcal changes from a behavioral perspective.

Yumei Yan¹, Govind Nair², Longchuan Li², Mark Wilson³, Xiaoping Hu², Mar Sanchez^4,5, and Xiaodong Zhang^1,3
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Biomedical Engineering, Emory University and Georgia institute of Technology, Atlanta, GA, United States, ³Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ⁴Department of Psychiatry & Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, United States, ⁵Psychobiology Division, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States

Optic nerve plays a critical role in the visual pathway and is nearly unmyelinated at birth. In this study, diffusion tensor imaging (DTI) was employed to characterize the optic nerve development in rhesus monkeys from infant (2 weeks old) to adulthood (6 years old). The progression of fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity followed an exponential trend, consistent with the white matter development in human brains. Also, the time to maturity of the diffusion parameters is comparable with the previous reports on postmortem examination of rhesus monkey optic nerves.

Peng Sun¹, Yong Wang¹, Teng-Nan Lin², and Sheng-Kwei Song^1
1Radiology, Washington University in St. Louis, Saint Louis, MO, United States, ²2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

DTI had been widely used to detect and characterize axonal injury and demyelination. However, diffusion parameters derived using DTI lose specificity and sensitivity with increasing pathological and anatomical complexity. Herein, diffusion basis spectrum imaging (DBSI) was employed to address DTI limitations resolving multiple-tensor water diffusion resulting from axon injury, demyelination, and inflammation in a rat stroke model of transient middle cerebral artery occlusion (MCAO). The current results suggest that DBSI may be used to more accurately reflect the underlying tissue destruction.

Seon Joo Kwon¹, Woo Hyun Shim¹, Bharat B Biswal², and Young Ro Kim^1
1Radiology, MGH, Charlestown, MA, United States, ²Radiology, New Jersey Medical School, Newark, NJ, United States

The typical CBV quantification strategy utilizes the systemic administration of MR contrast agents. In the current study, we propose to use breath hold (BH) and the associated tissue MRI signal changes to bypass the use of MR contrast agents and to enable the measurement repeatability. We compared the voxelwise CBV values acquired from the DSC (using Gd-DTPA) and BH methods in normal rat brains (n=6). The results from two techniques were significantly correlated, implicating that the BH technique can be used as a tool for quantifying CBV in replacement of traditional contrast agent methods.

Yu-Han Hong¹, Yi-Wen Peng², Yeu-Sheng Tyan^1,3, and Jun-Cheng Weng^1,3
1School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ³Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Characterizing complex anatomy at different stages of brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. Diffusion tensor tractography allows for the in vivo delineation of white matter tracts in the brain in a manner that is individualized to the particular neuroanatomy of each subject. Diffusion anisotropy and diffusivity change in some brain regions with demyelinating disease and also with neural development. However few studies identify these changes along the white matter tracts. Therefore the goal of this study was to characterize the changes of quantitative diffusion indices along white matter tracts in the developing rabbit brains. Along-tract method analyzes the quantitative diffusion indices associated with these virtual dissections in a way that is parameterized along the curving axes of the tract spines, instead of the more typical method of averaging this variation into a single mean estimate for each tract. In this study, DTI data of in vivo rabbit brains (4 weeks to 40 weeks) were acquired and analyzed. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in the regions of interest (ROIs) and along tracts were generated and compared across the ages. In our results, DTI tractography of the important white matter tracts, such as hippocampus, corpus callosum, and olfactory tract, showed refinement in regional tract architecture with maturation. Both regional and along-tract diffusion indices revealed these white matter tracts change during mature period.

Xiaojie Wang¹, Joong Hee Kim², Jenet O'Neal³, Shawn O'Neal⁴, Joan Brieland³, and Sheng-Kwei Song^2
1Chemistry, Washington University, Saint Louis, Missouri, United States, ²Radiology, Washington University, Saint Louis, Missouri, ³Exploratory Immunobiology, Pfizer Inc.,⁴Investigative Pathology, Pfizer Inc.

In vivo DTI was performed on experimental autoimmune encephalomyelitis (EAE) mice undergoing daily prophylactic (immediately after immunization) and therapeutic (immediately after disease onset) treatments of FTY720 at 3 and 10 mg/Kg. Axon and myelin integrity of lumbar segments was assessed using axial and radial diffusivity. Prophylactic treatment significantly reduced clinical scores of EAE mice while therapeutic treatment was only marginally effective. However, both treatments significantly preserved axon and myelin integrity based on in vivo axial and radial diffusivity measurements. The finding suggests that in vivo DTI may detect treatment effect before neurological evaluation responding to the disease modifying intervention.

Yohan van de Looij^1,2, Gregory A Lodygensky¹, Justin M Dean³, Henrik Hagberg³, Carina Mallard³, Petra S Hüppi¹, Rolf Gruetter^2,4, and Stéphane Sizonenko^1
1Division of Child Growth & Development, University of Geneva, Geneva, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Perinatal Center, University of Gothenburg, Göteborg, Sweden, ⁴Department of Radiology, University of Geneva and Lausanne, Geneva and Lausanne, Switzerland

Encephalopathy of prematurity is a major cause of developmental disabilities in up to 75% infants after preterm birth. The aim of this study was to characterize the changes in the developing sheep WM following fetal LPS exposure by MRI: T1W, T2W images and DTI as well as histopathology correlation. The combination of lesions observed in LPS treated fetal sheep mimics very well the pattern of injuries seen in premature infants. We show the excellent ability of DTI to classify different types of brain lesions following LPS exposure with specific changes of DTI derived between different lesions.

Manoj Kumar¹, Ilya M Nasrallah¹, Sungheon Kim², Ranjit P Ittyerah¹, John H Wolfe^3,4, Stephen Pickup¹, and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Radiology, New York University, New York, United States, ³Pathobiology and Pediatrics, University of Pennsylvania, Philadelphia, United States, ⁴Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

In-vivo and Ex-vivo diffusion tensor imaging (DTI) was performed on 22 week old MPS VII (n=6) and wild-type littermates (n=5) to assess abnormalities in the white matter areas of MPS VII mice. DTI data was processed and region of interest (ROI) analysis was performed from different gray and white matter regions of the brain using DTI studio software. Significantly reduced fractional anisotropy (FA) in corpus callosum and external capsule was observed in MPS VII affected mice as compared to wild type indicating reduced myelination. Luxol fast blue stains from these regions confirmed the presence of less compact and myelinated fibers in MPS VII brains. This preliminary data demonstrates the utility of DTI in observing microstructural abnormalities in brain of MPS VII mice. The study may be helpful in understanding the pathology of MPS VII and in assessing therapeutic response in these mice using DTI as a surrogate imaging biomarkers.

Ravi Gottumukkala¹, Tsen-Hsuan Lin^1,2, Yong Wang¹, Keun-Young Kim³, Won-Kyu Ju⁴, and Sheng-Kwei Song^1
1Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States, ²Department of Chemistry, Washington University School of Medicine, St. Louis, MO, United States, ³National Center for Microscopy and Imaging Research and Department of Neuroscience, University of California San Diego, La Jolla, CA, United States, ⁴Hamilton Glaucoma Center, University of California San Diego, La Jolla, CA, United States

A novel approach, diffusion basis spectrum imaging (DBSI), was used to noninvasively detect increased optic nerve cellularity as well as axon and myelin injury in the DBA/2J mouse model of glaucoma. DBSI-derived estimations of cellularity correlated with DAPI counts seen histologically (r = 0.86, p < 0.001). Axial and radial diffusivity changes in the optic nerves of DBA/2J mice were suggestive of axon and myelin injury, respectively. As the role of glaucomatous optic nerve gliosis is further elucidated, noninvasive quantification of optic nerve cellularity using DBSI could have clinical utility in diagnosis and prediction of therapeutic responses in glaucoma patients.

Chao-Yu Shen^1,2, Wei-Ya Tseng¹, Chu-Wen Chang¹, Hsi-Chang Chang³, and Jun-Cheng Weng^1,2
1School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ³Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung, Taiwan

Cognitive impairment and gait disturbance are the major side effects of radiation-induced white matter injury. Magnetic resonance imaging (MRI) has been widely used as a noninvasive modality for detection of brain lesions, but the characterization of the normal brain tissue to therapeutic dose radiation is still not well understood. The aim of our study was to longitudinally evaluate early-delayed radiation-induced changes of the brain white matter in a rabbit model after a single sub-lethal high dose irradiation (30 Gy) by using T2 weighted imaging (T2WI) and diffusion tensor imaging (DTI). To quantify the diffusion anisotropy, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were used. Results showed no significant change on T2WI but continuing decrease fractional anisotropy, early decreased axial diffusivity and late increased radial diffusivity in the follow-up time points. We suggested the DTI indices are more sensitive than T2WI and can reflect pathologic changes in radiation-induced brain white matter injury during early-delay phase.

Abby Y. Ding^1,2, Iris Y. Zhou^1,2, Frank Y. Lee^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China

Rapid eye movement (REM) sleep is believed to be critical for memory consolidation. To probe the microstructural changes after sleep deprivation (SD) in vivo, REM-SD and DTI were employed in this study. Significant axial, radial and mean diffusivity decreases were found bilaterally in various locations in hippocampus, suggesting specific layers of hippocampus such as dentate gyrus and CA1 may be more susceptible to SD. Significant FA, axial and mean diffusivity decreases were also detected in cortex. Our results indicated that DTI is sensitive for probing microstructural changes, and can provide insights into the microstructural plasticity associated with sleep and memory.

Yuki Mori¹, and Yoshichika Yoshioka^1
1Biofunctional Imaging, WPI IFReC, Osaka University, Suita, Osaka, Japan

Non-invasive monitoring of immune cells before/after neuroinflammatory conditions may lead to understand the mechanisms of brain injury and repair. We try to delineate the dynamics of immune cells in mouse brain using intravenous superparamagnetic iron oxide particles (SPIOs) enhancement. Intravenous SPIO-enhanced MRI has a great possibility for visualizing the recruitments and migrations of immune cells in mouse brain in vivo, even in the normal brain. Immune cells in the brain markedly increased in the inflammatory conditions. Our technique could contribute to establish the estimation method for treating brain injury and also maintenance in normal condition that target immune cells.

Ana Belen Martin-Recuero¹, Agnieszka Krzyzanowska², Pilar López-Larrubia¹, Carlos Avendaño², and Sebastian Cerdán^1
1Instituto de Investigaciones Biomédicas, Alberto Sols, Consejo Superior de Investigaciones Científicas, Madrid, Spain, ²Anatomy, Histology & Neuroscience, Medical School, Autonoma Univ. of Madrid, Madrid, Spain

Cerebral inflammation underlies the most prevalent and morbid pathologies, including cancer and neurodegeneration. A better understanding of inflammation processes paves the way for more accurate diagnoses and effective therapies. However, the imaging signatures of inflammation remain elusive, being many times difficult to discriminate from those derived from the underlying pathologies. To this end, we report here a longitudinal multi-parametric MRI characterization of cerebral inflammation after the systemic administration of lypopolisacharide (LPS). DWI, MT and T2 maps revealed selective hippocampal and cortical damage one day after the injection, increasing three days after in the hippocampus but disappearing in the cortex.

Hao-Hung Tsai^1,2, Ling-Yuh Shyu³, Chia-Ling Chi¹, Hui-Chen Tsai¹, Hsueh-Lin Li⁴, and Jun-Cheng Weng^1,2
1School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ²Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ³Department of Parasitology, Chung Shan Medical University, Taichung, Taiwan, ⁴School of Medicine, Chung Shan Medical University, Taichung, Taiwan

Angiostrongylus cantonensis (A. cantonensis) is a parasitic nematode which causes Angiostrongyliasis, the most common cause of eosinophilic meningitis in Southeast Asia and the Pacific Basin. The roundworm commonly resides in the pulmonary arteries and hearts of rats, giving it the nickname the rat lungworm. Snails are the primary intermediate hosts, where larvae develop until they are infective. Humans are incidental hosts and may become infected after ingestion of the worms in raw snails from contaminated vegetables. The typical clinical presentation is acute meningitis with an eosinophilic pleocytosis frequently accompanied by encephalopathy and other symptoms of central nervous system (CNS). Patients usually present an insidious or sudden onset of excruciating headache, neck stiffness, nausea, vomiting and paraesthesia. The diagnosis of eosinophilic meningitis can be arrived at through detection of elevated cranial pressure and increased volumes of eosinophils. The diagnosis of the cause of eosinophilic meningitis and the presence of A. cantonensis is remarkably more difficult. A spinal tap, or a sample of cerebrospinal fluid (CSF), must be taken to search for A. cantonensis worms or larvae. A. cantonensis is virtually undetectable in the CSF of half of the infected individuals. Current methods of detecting specific antigens associated with A. cantonensis are also unreliable. Therefore, the purpose of this study was to determine the longitudinal effects of rabbit brain infected with 700 larvae of A. cantonensis by advanced MRI techniques, and the results were verified by histopathological study.

Michael D. Boska¹, Mariano G Uberti¹, Prasanta Dash², Santhi Gorantla², Larisa Y Poleuktova², and Howard E Gendelman^2
1Radiology, University of Nebraska Medical Center, Omaha, NE, United States, ²Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE, United States

A humanized mouse model of HIV infection which replicates immune, virologic and neuropathologic features of human HIV infection was used to evaluate nervous system dysfunctions by diffusion tensor imaging. Analyses of the cortical region of the whisker barrels versus time over 16 weeks reveal mean absolute values of FA and _l remained relatively unchanged, _t increased, and FA decreased, a time course which was similar to unmanipulated controls. However, more careful analysis of the time course by time linear regression of individual results compared to virus levels reveal that higher viral loads, associated with brain pathology, reduced diffusivity and increased anisotropy.

Simon CHATELIN¹, Marie HUMBERT-CLAUDE², Valérie VILGRAIN¹, Bernard E Van BEERS¹, Zsolt LENKEI², and Ralph SINKUS^1
1U773-CRB3, INSERM, Paris, France, ²Laboratoire Neurobiologie et Diversité Cellulaire, ESPCI-CNRS, UMR7637, Paris, France

This study shows for the first time a significant temporal alteration of young rat brain mechanical properties after cannabinoïd injection by in vivo MR-Elastography. This effect is relevant in fiber-rich regions and a modification of their axonal structures can be supposed. It would confirm that CB1R receptors may play an important role in the regulation of structural plasticity and neuronal remodeling in the postnatal brain with significant effects on brain stiffness.

Chien-Hsiang Huang^1,2, Chiao-Chi V. Chen², Sheng-Hsiou Hsu², Fu-Shan Jaw¹, and Chen Chang^2
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Cerebral microvascular aberrations are increasingly recognized as a major disturbance in brain disorders, including Huntington¡¦s disease (HD). To appreciate such abnormalities, approaches sensitive to the detection of small vessel changes are necessary. In this study, a new 3D microscopic magnetic resonance angiography was developed based upon the intrinsic BOLD contrast. This new method does not require the use of contrast agents and thus is highly practical in the clinical settings. We demonstrate herein the sensitivity and usefulness of this new tool to longitudinally monitor the abnormal microvasculature in mice with HD.

Lauri Juhani Lehto^1,2, Alejandra Sierra¹, Curt Corum², Djaudat Idiyatullin², Asla Pitkänen¹, Michael Garwood², and Olli Gröhn^1
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Eastern Finland, Finland, ²Center for Magnetic Resonance Research, University of Minnesota, United States

Many diseases involve myelin loss in white matter. Myelin and myelin water has been related to short T2 components, that can be invisible to conventional MRI sequences due to relatively long TE. SWIFT, an almost zero acquisition delay sequence can detect these components. SWIFT was used to study dysmyelination in traumatic brain injury rat model ex vivo. Changes in TBI animals were detected through normal, long T2 and subtraction images. Although SWIFT does not have a TE, it has been shown to have phase contrast that was also investigated. White matter changes were detected in several structures confirmed by histology.

Stefano Lepore^1,2, Helmar Waiczies^1,2, Jan Hentschel², Jason M. Millward^3,4, Carmen Infante-Duarte^3,4, Thoralf Niendorf^2,4, and Sonia Waiczies^1,2
1Ultrahigh Field Imaging in Neuroinflammation, Experimental and Clinical Research Center (ECRC), a cooperation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Berlin, Germany, ²Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck-Center for Molecular Medicine, Berlin, Berlin, Germany, ³Experimental Neuroimmunology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ⁴Experimental and Clinical Research Center (ECRC), Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany

Microscopic MRI enables the acquisition of highly resolved images in a reasonable scan time, thereby providing the possibility to perform in vivo longitudinal studies in animal models. In this study we have detected and tracked early structural changes in brain tissue of EAE mice prior to neurological symptoms. We were able also to detect a significant enlargement of the ventricles before disease onset and an increase in T₂ relaxation time of CSF after disease onset. Microscopic MRI and T₂ maps provide the opportunity to better understand the early processes involved in the development of encephalomyelitis.

Michael Valdez¹, Eriko Yoshimaru¹, Pier Ingram², John Totenhagen¹, Aaron Forbes³, Stephen Moore¹, Paul Helquist³, Terry Matsunaga², Russel Witte², Lars Furenlid^2,4, Zhonglin Liu², Robert Erickson^5,6, and Theodore Trouard^1,2
1Biomedical Engineering, University of Arizona, Tucson, Arizona, United States, ²Radiology, University of Arizona, Tucson, Arizona, United States, ³Chemistry, University of Notre Dame, ⁴Optical Sciences, University of Arizona, Tucson, Arizona, United States, ⁵Pediatrics, University of Arizona, Tucson, Arizona, United States, ⁶Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, United States

Treatment of neurological disorders is often hampered by the inability of drugs to get across the blood-brain barrier (BBB). Novel techniques have been developed that use ultrasound in combination with microbubble contrast agents to reversibly open up the BBB for drug delivery. We have combined these techniques with high-resolution -ray imaging to directly image the crossing of radiolabeled beta-cyclodextrin, a promising new therapy for Niemann-Pick type C disease, into the brains of mice in vivo.

Dana S Poole¹, Johannes R Sikkema¹, Julien Milles¹, Matthias J.P. van Osch¹, Arn M.J.M. van den Maagdenberg^2,3, and Louise van der Weerd^1,4
1Radiology, Leiden University Medical Centre, Leiden, Zuid Holland, Netherlands, ²Human Genetics, Leiden University Medical Centre, ³Neurology, Leiden University Medical Centre, ⁴Anatomy and Embriology, Leiden University Medical Centre

The purpose of this study was to investigate the impact of the osmolarity and dose of the contrast agent (CA) on the estimation of the BBB damage, to identify optimal conditions for detecting low/uncertain BBB disruption and to provide an improved protocol therefor. Two different gadolinium-based contrast agents have been employed for this purpose – gadoliniumtetraazacyclododecanetetraacetic acid (Dotarem®), and gadoteridol (ProHance®). A high CA dose is required to ensure the visualization and quantification of areas characterized by mild BBB disruption, but a high osmolarity of the contrast agent can aggravate BBB damage. Our optimized protocol represents a combination of maximum dosage and iso-osmolarity of CA.

Matthew D Budde¹, L. Christine Turtzo², Eric Gold², Lindsay Janes³, Bobbi Lewis³, and Joseph A Frank^2,3
1Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Center for Neuroscience and Regenerative Medicine, Bethesda, MD, United States,³Clinical Center, National Institutes of Health, Bethesda, MD, United States

We sought to investigate whether dynamic contrast enhanced (DCE) MRI could be used to monitor BBB disruption in a rat model of TBI and whether interferon beta-1b, a drug that stabilizes the blood brain barrier (BBB) and has anti-inflammatory properties, would be effective. Although the BBB was severely disrupted between 30 minutes and 7 days following injury, it did not correlate with outcome, nor did interferon beta-1b affect alter disease course. DCE effectively monitors vascular injury following TBI, but significant challenges remain in modulating the injury.

Taeko Inoue¹, Tabassum Majid², Ann Quick¹, Christine Beeton^1,2, and Robia G Pautler^1,2
1Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, United States, ²Translational Biology & Molecular Medicine, Baylor College of Medicine, Houston, TX, United States

Multiple Sclerosis (MS) is a demyelinating disease of the Central Nervous System. It is slow progressing and ultimately results in debilitation of afflicted individuals. It is characterized by periods of relapse and remission of neurological symptoms that include decreased vision, muscle weakness and coordination loss. The etiology of MS is currently unknown, however, it is understood that autoimmune mechanisms involving elevations in reactive oxygen species are involved in the development of lesions. As a result, we hypothesized that lowering of ROS by overexpressing an antioxidant, superoxide dismutase-2 in an EAE model of MS would result in decreased EAE phenotype.

Mathieu David Santin^1,2, Thomas Debeir³, Sharon Lori Bridal⁴, Thomas Rooney³, and Marc Dhenain^1,5
1Laboratoire des maladies neurodégénératives, URA 2210 CEA/CNRS, Fontenay-aux-Roses, France, ²Centre de NeuroImagerie de Recherche (CENIR), Institut du Cerveau et de la Moëlle Epinière, Paris, France, ³Therapeutic Strategic Unit Aging, Sanofi-Aventis, Chilly-Mazarin, France, ⁴Laboratoire d'Imagerie Paramétrique, UMR 7623 CNRS/UPMC, Paris, France, ⁵MIRCen, CEA / I2BM, Fontenay-aux-Roses, France

This work presents a new imaging technique for in vivo detection of amyloid plaques, the main lesions of Alzheimer's disease. In transgenic mouse model of Alzheimer's disease, we combined techniques based on MRI Gd-staining method with transient opening of the blood brain barrier thanks to ultrasound (US). The images obtained with our new imaging protocol (US-Gd Staining) were compared with our previously published reference protocol consisting on an intracerebroventricular injection of an NMR contrast agent (ICV-Gd-Staining). Our new protocol allows in vivo amyloid plaque detection after an IV injection of an NMR contrast agent.

Krithika Balasubramanian¹, Anjali Chauhan², Uma Sharma¹, Senthil S Kumaran¹, Yogendra K Gupta², and Naranamangalam R Jagannathan^1
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India, ²Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, Delhi, India

Sequential monitoring of motor activity was carried out using four motor coordination tests in rats with lysophosphatidyl choline induced demyelination during different stages of the disease progression and regression. The results were correlated with T1 and T2 relaxation times measured at 4.7 T which increased during the progression of demyelination and subsequently decreased and reached normal values during remyelination. Activity on photoactometer, rotarod and grip strength showed negative correlation with T1 and T2 while foot fault test showed a strong positive correlation with the relaxation times. Thus MR parameters aid in understanding the pathophysiology of demyelination.

Geon-Ho Jahng¹, Sung Ho Lee², Min-Ji Kim¹, Hyug-Gi Kim¹, Chang-Woo Ryu¹, Sun Mi Kim¹, Dal Mo Yang¹, Dong Wook Sung³, Woo-Suk Choi³, Il Whan Choi⁴, Chi-Bong Choi³, and Hwi-Yool Kim^2
1Radiology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Seoul, Korea, ²Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Korea, ³Radiology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Seoul, Korea, ⁴Meridian and Acupuncture, Graduate School of Applied Eastern Medicine, Kyung Hee University, Seoul, Korea

To investigate the interruption of a neuronal pathway during a passive moving task (PMT) by acupuncture insertion at ST36 acupoint in the normal and Parkinson¡¯s disease (PD) dog model, we developed a novel method to model PD dog. 8 healthy beagle dogs were divided into 2 groups of 4 dogs each, a normal control and a PD model group. During fMRI, the PMT was performed during three different sessions, which consisted of PMT only (MO), PMT with inserting an acupuncture needle at the ST36 acupoint (TA), and PMT with inserting the needle at a sham point (SA).

Istvan Pirko¹, Jeffrey D. Gamez¹, Mihajlo Babovic², Moses Rodriguez¹, and Slobodan I. Macura^3
1Department of Neurology, Mayo Clinic, Rochester, MN, United States, ²Carleton College, Northfield, MN, United States, ³Department of Biochemistry, Mayo Clinic, Rochester, MN, United States

The MRI-clinical paradox in MS refers to T2 weighted lesion load showing poor disability correlation. The reasons include non-specificity of T2 weighted lesions, no consideration of lesion location, and insensitivity to NAWM and NAGM pathology. We characterized 2 murine models of progressive MS: in model (A), lesion load developed linearly with strong disability correlation. In model (B) disability correlation was poor in the early (“tumefactive”) and strong in the late (“regular”) stage. Brainstem lesion load correlated best with disability in both models. These models are suitable for future studies characterizing NAWM, NAGM and studies of novel treatment strategies in MS.

Haiying Tang¹, Asamoah Bosomtwi², shalini Jaiswal¹, Sanjeev Mathur², Kimberley Byrnes³, and Reed Selwyn^1
1Radiology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ²Center for Neuroscience and Regenerative Medicine (CNRM), HJF, Bethesda, MD, United States, ³Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

The present pre-clinical multi-modal imaging integrates the emerging molecular imaging (PET) and MRI techniques to assist the traumatic brain injury (TBI) research using the rat model of TBI. We propose to investigate the post-injury metabolism changes in injured brains using the deoxyglucose (18F) (FDG) micro PET imaging (mPET). MR imaging techniques including the T1/T2/T2*/diffusion/perfusion MRI, susceptibility weighted imaging (SWI), and MR spectroscopy (MRS). These provide comprehensive information at the structural and functional levels that can help us investigate imaging markers of disease progression, white matter degeneration, vascular abnormalities, and micro-hemorrhages following TBI. PET and MR images are spatially co registered. Correlations between changes in glucose metabolism and MRI perfusion and diffusion in various brain regions and in lesion and perilesional regions in rats that undergo mild-moderate TBI are investigated.

Marianne Dorothea Keller¹, Nyoman Kurniawan¹, Kerstin Pannek¹, Stephen Edwards¹, Stephen Rose¹, Maree Smith¹, Elizabeth Coulson¹, and Ian Brereton^1
1The University of Queensland, Brisbane, Qld, Australia

The cholinergic hypothesis states that dysfunction of acetylcholine containing neurons cause the cognitive decline in Alzheimer's disease patients. This project used tractography in a transgenic mouse model (APP/PS1). The transgenic model develops a large Amyloid- plaque load. We found significant changes due to axonal degeneration of cholinergic fibres that have their origin in the basal forebrain.

Joanna K Huttunen¹, Antti M Airaksinen¹, Artem Shatillo¹, Juha-Pekka Niskanen^1,2, Asla Pitkänen^3,4, and Olli Gröhn^1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ²Department of Applied Physics, University of Eastern Finland, Kuopio, Finland, ³Dept. of Neurobiology, Epilepsy Research Laboratory, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ⁴Department of Neurology, Kuopio University Hospital, Kuopio, Finland

The aim of the study was to investigate the origin of the kainic acid (KA) induced epileptic seizures after traumatic brain injury (TBI) utilizing simultaneous local field potential (LFP) and fMRI measurements. In all animals, KA induced seizures caused detectable responses in BOLD and LFP signals. The first epileptic seizure elicited BOLD response initially in the cortex before activating the hippocampus.

Diana Cash¹, Winfred Chege¹, Michel SB Mesquita¹, Nadia N Malik², Mark D Tricklebank², Michael J O'Neill², and Steven CR Williams^1
1Neuroimaging, King's College London, London, United Kingdom, ²Eli Lilly and Co., United Kingdom

Serial structural MRI of rat MAM model of schizophrenia was conducted until the rats were 1 year of age, showing overall reduction in hippocampal and brain volumes, as well as a reduction of cortical thickness. Pharmacological MRI was conducted in aged rats at 12 months of age, showing a different response to an NMDA antagonist ketamine in MAM rats vs. shams.

Taifeng Lin¹, Maobin Wei¹, Zhiwei Shen¹, Gang Xiao¹, Renhua Wu¹, and Phillip Zhe Sun^2
1Shantou University Medical College, Shantou, Guangdong, China, ²Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States

pH-sensitive magnetization transfer (MT) imaging can reflect the alteration in metabolism. Using this technology to image ischemic brain may make an early detection and prediction of ischemic penumbra. Twelve male cats underwent permanent MCAO, and ischemic evolution was observed at a clinical 1.5 T scanner through clinical T1WI, T2WI, DWI and MT-imaging. We found that in 5 of 12 animals hypointensity in occlusion side was displayed on MT-imaging, when there was no any alteration on the clinical images yet. In other 7 of 12 animals, we could observe the intensity alterations in DWI and MT-imaging at the same time. We also found that pH-sensitive MT-imaging was sensitive to detect infarction prior to current clinical sequences and might be able to predict ischemic penumbra.

Zhigang You¹, and Wingchi Edmund Kwok^1
1Department of Imaging Sciences, University of Rochester, Rochester, NY, United States

For rat brain MRI studies, clinical scanners offer the advantages of reducing field inhomogeneity and susceptibility artifacts associated with high-field small-bored systems and the studies are more translational for human applications. However, obtaining sufficient SNR and resolution on clinical scanners is challenging. Therefore, we developed a dedicated 3D-orthogonal phased-array receive coil for rat brain imaging at 3T. Compared to a commercial 4cm surface coil, our coil provides higher and more uniform signal, significantly improving image quality and resolution. Our coil is also compatible with parallel imaging to reduce scan time. It should be useful for high-resolution imaging of rat brain.

Eric R Muir¹, Damon Cardenas¹, Guang Li¹, John Roby¹, and Timothy Duong^1,2
1Research Imaging Institute, UT Health Science Center, San Antonio, TX, United States, ²Ophthalmology, UT Health Science Center

Oxygen has several effects on MRI signals including T1 shortening, T2/T2* BOLD effects from hemoglobin, and the Bo field may be altered by paramagnetic oxygen. Oxygen is increased under hyperbaric conditions which have been used to treat various conditions, so MRI of subjects within hyperbaric chambers may therefore be affected. The goal of this study is to characterize the effects of normobaric and hyperbaric conditions on T1, T2, T2*, and Bo. These parameters changed only slightly, indicating that MRI under hyperbaric conditions should not be dramatically affected, paving the way for functional MRI studies under hyperbaric pressure.

Nyoman D. Kurniawan¹, Zhengyi Yang¹, Kay Richards², Fernando Calamante³, Jeremy F.P. Ullmann¹, Graham J. Galloway¹, Steven Petrou², and David C. Reutens^1
1Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia, ²Florey Neuroscience Institutes, University of Melbourne, Melbourne, Victoria, Australia, ³Florey Neuroscience Institutes, Brain Research Institute, Melbourne, Victoria, Australia

The functional organization, development and plasticity of the barrel cortex are of great interest in neuroscience. In this study, we present a novel method using directional encoded color short tracks track-density imaging (DECst TDI) to show the structure of barrel cortex from ex-vivo samples.

Lauri Lehto¹, Curtis Corum², Djaudat Idiyatullin², Asla Pitkänen^1,3, Michael Garwood², Olli Gröhn¹, and Alejandra Sierra^1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Kuopio, Finland, ²Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical, Minneapolis, Minnesota, United States, ³Department of Neurology, Kuopio University Hospital, Kuopio, Finland

Intracranial hemorrhage is a consequence of traumatic brain injury (TBI). Bleeding is the result of mechanical damage, triggering secondary events, such as neuronal hyperexcitability, toxicity, or inflammation. The accumulation of blood in brain tissue results in high iron content deposits, which are paramagnetic and detectable by MRI. To study iron deposits after TBI, we utilized SWIFT (sweep imaging with Fourier transformation), that is an almost zero acquisition delay pulse sequence using gapped frequency swept pulses. Even though there is no time for phase accumulation at k=0, as during a gradient echo, phase behavior is still seen in the acquired data.

Susan M. Motch¹, Thomas Neuberger^2,3, Neus Martínez-Abadías¹, Talia L. Pankratz¹, Yingli Wang⁴, Ethylin W. Jabs⁴, Timothy M. Ryan¹, and Joan T. Richtsmeier^1
1Department of Anthropology, The Pennsylvania State University, University Park, PA, United States, ²Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, United States, ³Department of Bioengineering, The Pennsylvania State University, University Park, PA, United States, ⁴Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, New York, NY, United States

We used µMR and µCT images of littermates of the Fgfr2cC342Y/+ mouse model for Crouzon/Pfeiffer syndromes, to investigate the global and regional impact of this mutation on the developing negative spaces of the head and skull at P0. Volumetric measurement using µMR images indicated restriction of the nasopharynx of Fgfr2cC342Y/+ mice (n=8) compared to non-mutant littermates (n=11), but no difference in cochlear and semicircular canal volume. Global and regional (cranial vault, cranial base, facial skeleton) differences in skull morphology were observed using configurations of 3D landmark coordinates measured on µCT isosurfaces in Fgfr2cC342Y/+ mice (n=28) relative to non-mutant littermates (n=31).

Sveinung Fjær^1,2, Stig Wergeland^1,2, and Lars Bø^1,2
1The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway, ²Department of Clinical Medicine, University of Bergen, Bergen, Norway

In multiple sclerosis and other demyelinating disorders of the central nervous system assessment of change in myelin content would be an important clinical tool. Magnetization Transfer Ratio (MTR) is a semiquantitative MR technique for detecting macromolecules, like myelin. In this study we have developed a guided semi-automatic method for detecting regional MTR change in the mouse brain. By comparing MTR change to histopathology we show that MTR can detect myelin change in several regions of the mouse brain, including deep gray matter.

Vaibhav Anil Janve^1,2, Zhongliang Zu¹, Song-yi Yao³, Ke Li¹, Fang Lin Zhang³, Kevin Wilson¹, Xiawei Ou⁴, Mark Does^1,5, Subramaniam Sriram³, and Daniel Gochberg^1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Department of Physics, Vanderbilt University, Nashville, TN, United States, ³Department of Neurology, Vanderbilt University School of medicine, Nashville, TN, United States, ⁴Department of Radiology, Arkansas Children's Hospital, ⁵Radiology and Radiological Sciences, Vanderbilt University

We present correlation of high-resolution 3D qMT and DTI matrices with reconstructed quantitative 3D myelin histology volume in a lipopolysacharide (LPS) mediated animal model of MS. We seek to develop an animal model system of type III oligodendrogliopathy which is seen in the relative absence of prominent lymphocytic infiltration. To our knowledge this is the first quantitative magnetic resonance myelin study of an animal model of Type III MS lesions. We find qMT measured apparent pool size ratio (PSR) and DTI measured radial diffusivity (RD) shows the strong correlation with histological measure of myelin content.

Puneet Bagga¹, and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

There is a rapid increase in the number of neurons and synapse formation in the brain during postnatal development with glutamatergic and GABAergic neurons undergoing large increases in neurotransmitter cycling and oxidative energy metabolism. Whereas, no or little information is available for astroglial activity during this period. Male SD rats were studied at P10 and P30 by infusing [2-¹³C]acetate and ¹H-[¹³C]-NMR Spectroscopy. In addition to remarkable neurochemical changes, acetate utilization was found to be increased by three folds at P30 indicating increased astroglial activity during postnatal period.

Keigo Hikishima^1,2, Kazuhiko Sawada³, Yuji Komaki^1,2, Ayako Murayama², Kenji Kawai¹, Nanako Sato¹, Takashi Inoue¹, Toshio Ito¹, Suketaka Momoshima⁴, Hirotaka James Okano⁵, Erika Sasaki¹, and Hideyuki Okano^2
1Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan, ²Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan, ³Tsukuba International University, ⁴Department of Radiology, Keio University School of Medicine, ⁵Division of Regenerative Medicine, Jikei University School of Medicine

The common marmoset, a small New World primate species, has been widely used in neuroscience research. It is essential to evaluate and characterize the brain organization during pre- and post-natal development non-invasively. However, little is known about either brain morphology or even imaging techniques. We reported time-course and high-resolution MRI of the developing brain in the marmoset and advanced visualization in the changes of cortical thickness and fiber structure of commissure bundles using diffusion tensor imaging.

Brian J Nieman^1,2, Brian B Roman³, Kathleen J Millen⁴, and R Mark Henkelman^1,2
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Division of Biological Sciences, University of Chicago, Chicago, IL, United States, ⁴Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA, United States

The mammalian brain and skull develop concurrently. Large variations in one of these structures are frequently accompanied by morphological changes in the other. We use a combination of MRI and computed tomography for deformation-based analysis of the brain and skull in a mouse model of Dandy-Walker syndrome. We show that the deformations between the average and wildtype mice on the brain surface closely follow the deformations seen on the inside of the skull. This indicates a tight fit between brain and skull. These tools will be important for assessing alterations or disease where the concurrent development is interrupted.

Peter S LaViolette¹, Andrew C Discolo¹, Kimberly A Pechman², and Kathleen M Schmainda^1,3
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ³Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

We have developed a technique to precisely quantify and compare histology to MRI on a voxel-wise basis. We demonstrate its utility in a U87 rat brain tumor model, where we compare relative cerebral blood volume (rCBV) as measured with dynamic susceptibility contrast (DSC) MRI to ex vivo von Willebrand factor (vWF) expression.