Characterization of White Matter in Disease
Tuesday 21 April 2009
Room 311 10:30-12:30


Kelvin O. Lim and Karen A. Tong

10:30  242. White Matter NAA Levels and Very Long Chain Fatty Acid Levels in Asymptomatic Boys with X-Linked Adrenoleukodystrophy Undergoing Lorenzo’s Oil Therapy

Asif Mahmood1,2, Gerald V. Raymond1,2, Michael J. Moser3, Peter B. Barker2,3
Neurology, Johns Hopkins University, Baltimore, MD, USA; 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Radiology, Johns Hopkins University, Baltimore, MD, USA

    Serial, yearly proton MRSI was performed in 58 asymptomatic boys with X-linked adrenoleukodystrophy (ALD) enrolled in a clinical trial of the dietary therapy “Lorenzo’s oil”. Metabolite ratios were examined for correlations with peripheral very long chain fatty acid (C26) levels. Significant negative correlations were found between posterior white matter NAA/Cho and NAA/Cr ratios and C26. These studies confirm preliminary results in a smaller number of subjects, which suggest that lack of control of C26 levels leads to axonal damage or dysfunction in the key white matter regions in ALD.
10:42 243. Increased NAA Concentration in the Restless Legs Syndrome: Possible Link to Hypomyelination

Byeong-Yeul Lee1, Padmavathi Ponnuru2, James R. Connor2, Qing X. Yang1,3
Bioengineering, The Penn State University, Hershey, PA, USA; 2Neurosurgery, The Penn State University, Hershey, PA, USA; 3Radiology, The Penn State University, Hershey, PA, USA

    Iron deficiency has been known as a contributing factor for restless legs syndrome (RLS). To date, the relationship of iron deficiency and neurochemical changes in the dopaminergic brain structures has not been studied in vivo. The aim of present study was to investigate the neurochemical profiles in the RLS brain using in vivo 1H MRS as well as ex vivo myelin analysis of RLS autopsy brain tissue. We observed a highly significant increase in NAA concentration and decreased expression of myelin-related protein in RLS brain. These results support the hypothesis that brain iron deficiency may cause hypomyelination which leads to a NAA increase in RLS brain.


10:54 244.

Alteration of T2 Relaxation and NAA Concentration in Schizophrenia Evaluated in Frontal White Matter at 3 T

    Nuran Tunc-Skarka1, Wolfgang Weber-Fahr1, Mareen Hoerst1, Susanne Englisch2, Christine Esslinger2, Dragos Inta2, Alexander Guttschalk2, Mathias Zink2, Gabriele Ende1
Department Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; 2Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
    There are several studies that found reduced NAA in schizophrenic patients. This could be an indication that NAA concentration or relaxation might be different due to pathological microstructure changes. The major problem of individual metabolite relaxation time estimation is the long measurement time. Nevertheless, only with the knowledge of individual relaxation time it is possible to evaluate absolute concentrations. In this study we wanted to estimate absolute metabolite concentrations of the frontal white matter in schizophrenic patients while evaluating individual T2 relaxation time and to compare with healthy controls. We found differences in NAA concentration and T2 relaxation time.
11:06 245. Investigation of Tract-Specific Myelin Content Measures from a Population Averaged Myelin Water Fraction Atlas
    Sean CL Deoni1
Centre for Neuroimaging Sciences, London, UK
    Here we report on the development of a whole-brain, population-averaged atlas of myelin content derived from in vivo measurements of the myelin water fraction. 14 healthy individuals were imaging using the mcDESPOT multi-component relaxometry technique, non-linearly coregistered to standard space and averaged. From the resulting whole-brain atlas we demonstrate white matter tract-specific measures and consider the future application of such an atlas for identifying disease-related change.


11:18 246. Evaluation of Anatomical and Functional Connections Following Traumatic Brain Injury in Humans by Diffusion Tensor Imaging and Resting-State Functional Connectivity
    Christine L. MacDonald1, Nicholas Hubbard1, Sanjeev Vaishnavi1, Adrian Epstein1, Abraham Snyder1, Stephanie Chleboun2, Joshua Shimony1, Marcus Raichle1, David Brody1
Washington University, Saint Louis, MO, USA; 2Southern Illinois University Edwardsville, Edwardsville, IL, USA
    Diffuse axonal injury is hypothesized to be the primary cause of cognitive deficits following traumatic brain injury (TBI). Currently clinical imaging modalities are not optimized to assess this pathology. 20 chronic TBI patients and 12 controls were scanned with diffusion tensor imaging and resting-state fMRI at 3T. Detailed neuropsychological assessments were performed the same day. Highly significant correlations were found between several aspects of cognitive performance and imaging abnormalities detected on DTI or resting-state fMRI analysis of functional connectivity. Conventional anatomical sequences did not reveal these pathologies. Thus, these advanced MRI techniques could be synergistically used to better assess TBI.
11:30 247. Application of Diffusion Tensor Imaging to Better Understanding Pathogenesis of the Pelizaeus-Merzbacher Disease
    Jeremy J. Laukka1,2, Malek I. Makki3, James Y. Garbern1,4
Neurology, Wayne State University, Detroit, Mi, USA; 2Radiology, Michigan State University, East Lansing, Mi, USA; 3Radiology, Wayne State University, Detroit, Mi, USA; 4Molecular Medicine and Genetics, Wayne State University, Detroit, Mi, USA
    Twelve Pelizaeus-Merzbacher disease (PMD) patients with a range of PLP1 mutations were analyzed by DT-MRI. The radial (ėradial) and parallel (ė//) diffusivities, apparent diffusion constant (ADC) and fractional anisotropy (FA) were measured through several white matter tracts, including the corpus callosum and corticospinal tract. The most dramatic difference between PMD patients and controls was increased ėradial, most marked in the corpus callosum. Interestingly, ė// was also increased in the severely affected PMD patients, whereas in severely dysmyelinated rodents, the ėradial is reported to be normal to decreased. ė// in patients with PLP1 null mutations was relatively unaffected relative to controls.


11:42 248. Microbleed Detection in Traumatic Brain Injury at 3T and 7T: Comparing 2D and 3D Gradient-Recalled Echo (GRE) Imaging with Susceptibility-Weighted Imaging (SWI)
    Kathryn E. Hammond1,2, Janine M. Lupo1, Duan Xu1, Sri Veeraraghavan1, Hana Lee3, Adam Kincaid3, Dan B. Vigneron1,2, Geoffrey T. Manley3, Sarah J. Nelson1,2, Pratik Mukherjee1
Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), CA, USA; 2UCSF/UCB Joint Graduate Group in Bioengineering; 3Neurological Surgery, UCSF
    The detection of microbleeds is important for the diagnosis and prognosis of traumatic brain injury (TBI). This study evaluated whether SWI improved microbleed detection over 2D or 3D GRE in 24 TBI patients scanned at 3T or 7T. The study reports that microbleeds were readily detectable in the short 2D GRE images, that few or no additional microbleeds were detected in the 3D GRE or SWI and that stretching in the SWI mislocated microbleeds. It concludes that the longer scan times required for 3D GRE and SWI may therefore not be necessary for clinical practice at high field.
11:54 249. Analyzing White Matter Integrity Changes Associated with Posttraumatic Stress Disorder in Veterans

Wang Zhan1, Zhen Wang2,3, Charles Marmar2, Thomas Neylan2, Yu Zhang1, Susanne Mueller1, Marzieh Nezamzadeh1, Chris Ching1, Michael Weiner1, Norbert Schuff1
1Department of Radiology, University of California, San Francisco, San Francisco, CA, USA; 2PTSD Research Program, VA Medical Center, San Francisco, CA, USA; 3Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China

    Diffusion tensor imaging (DTI) technique is applied to analyze the white matter (WM) integrity alterations in war-related posttraumatic stress disorder (PTSD) in male veterans. Voxel-based group comparisons are made between PTSD veterans and age-matched healthy veterans controls. PTSD related WM degradations, measured by reduced fractional anisotropy (FA), are detected in WM tracts in prefrontal cortex (PFC) and anterior cingulate cortex (ACC). In the PTSD group, reduced FA is also found to be significantly correlated with increased PTSD severities, and the decreased volumes of hippocampal subfield CA3 and dentate gyrus (CA3&DG).


12:06 250. White Matter Microstructure Abnormality in Autism Spectrum Disorders : A DTI Based Subdivided Corpus Callosum Study
    Pei-Chin Chen1, Kun-Hsien Chou2, I-Yun Chen3, Chun-Yi Lo1, Hsuan-Hui Wang1, Ya-Wei Cheng3, Ching-Po Lin1,3
Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; 2Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; 3Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan
    Autism spectrum disorders (ASD) is a heterogeneously neurodevelopmental disorder, that is characterized by impaired social reciprocity, communication difficulties, and restricted interest. To observe the abnormal brain connectivity in ASD, the investigation of subdivision corpus callosum using DTI fiber tracking with fractional anisotropy (FA), can indicate the integrity of the fiber tracts. The ASD had greater FA in the Region 4 and 5 than healthy subject, the result indicated that the communication between bilateral hemispheres was abnormal in motor, somaesthetic areas. Previous studies indicated abnormal regulation of brain growth in ASD results from early overgrowth followed by abnormally slowed growth.