Atlas-Based Approach to Study White Matter Disruption in Alzheimer’s Disease
Xin Fan¹, Guanghua Xiao², Kristin Martin-Cook³, Roger Rosenberg³, Myron Weiner⁴, Hao Huang^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States; ³Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States; ⁴Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States

Conventional VBM (voxel-based-morphometry) approaches delineate the abnormality at the voxel level. However, it is the information reflected from whole white matter tracts that have clinical importance. In this study, with no a priori information, this novel atlas-based approach has been used to examine fractional anisotropy (FA) of DTI of all 50 major white matter tracts at the tract level to detect white matter disruption in Alzheimer disease (AD). The proposed method is highly efficient, accurate, makes comprehensive examination of all major tracts and allows comparison of disruption level of these tracts.

Converging Microstructural Evidence in Prodromal and Early Alzheimer’s Disease: Alteration of Commissural and Association Pathways, Sparing of Motor Pathways
Gwenaelle Douaud¹, Saad Jbabdi¹, Timothy Edward Behrens¹, Ricarda Menke¹, Achim Gass², Andreas Monsch³, Anil Rao⁴, Brandon Whitcher⁴, Gordon Kindlmann⁵, Paul M. Matthews⁴, Stephen Smith^1
1FMRIB Centre, University of Oxford, Oxford, Oxfordshire, United Kingdom; ²Departments of Neurology and Neuroradiology, University Hospital, Basel, Switzerland; ³Memory Clinic, Basel, Switzerland; ⁴GSK, CIC Hammersmith Hospital, London; ⁵Department of Computer Science and Computation Institute, University of Chicago, Chicago, IL, USA

Using TBSS, we investigated white matter abnormalities in the largest diffusion study including healthy elderly, mild cognitive impairment and Alzheimer’s disease. We also used the ‘mode’ of anisotropy which specifies the shape of anisotropy. All diffusion tensor indices converged to show that the uncinate fasciculus, cingulum bundle, corpus callosum, anterior commissure and superior longitudinal fasciculus were affected.  We found a regional increase of mode and fractional anisotropy, often considered atypical for a degenerative disorder. Using tractography, we directly and quantitatively showed that these local increases were related to the neuropathological sparing of the motor-related pathways compared with the superior longitudinal fasciculus.

Gender Differences in the Dependence of Body Weight and Brain Connectivity Revealed by Diffusion Tensor Imaging
Karsten Mueller¹, Alfred Anwander¹, Annette Horstmann¹, Franziska Busse², Burkhard Pleger¹, Joeran Lepsien¹, Michael Stumvoll², Arno Villringer¹, Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; ²Department of Medicine, University Hospital Leipzig, Germany

We revealed gender differences in the dependence between body weight and brain structure using diffusion tensor imaging. For the female volunteers, we observed a significant negative correlation between the body mass index (BMI) and fractional anisotropy (FA) in all parts of the corpus callosum. This correlation could not be found for male subjects. A negative correlation between BMI and axial diffusivity was significant for both  women and men. An additional effect was found for the female participants only: A positive correlation between BMI and radial diffusivity. The underlying physiological reasons are still unclear and need to be further investigated.

Diffusion Tensor Imaging of Time-Dependent Axonal and Myelin Degradation After Carbon Monoxide Intoxication: White Matter Tract-Specific Quantification by Tract Probabilistic Map
Chun-Yi Lo¹, Wei-Che Lin^1,2, Chih-Hsueh Wang¹, Ai-Ling Hsu³, Ching-Po Lin^1,3
1Institute of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan; ²Departments of Diagnostic Radiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan; ³Institute of Brain Science, National Yang Ming University, Taipei, Taiwan

Patients with acute carbon monoxide (CO) intoxication may develop progressive white matter (WM) demyelination. We created WM parcellation atlas-based probabilistic maps of 5 major WM tracts. Automated tract-specific quantification of DTI parameters were performed to evaluation WM tract damage and the chronologic change in 17 patients with CO intoxication. The results revealed that decreasing fractional anisotropy were primarily driven by increasing radial diffusivity, which appeared to be more strongly correlated with demyelination in the initial presentation. Our finding supplements previous MRI studies by adding a level of anatomic detail to the relationship between white matter damage and cognitive dysfunction.

2D Distribution Analysis of DTI in Two Phenotypes of Dystonia Patients
An Vo¹, Miklos Argyelan¹, David Eidelberg¹, Aziz M. Ulug^1
1The Feinstein Institute for Medical Research, Manhasset, NY, United States

Hereditary dystonia is a neurological movement disorder where the subjects have abnormal motions due to muscle contractions.  We used a 2D distribution analysis with a physical brain model, which can automatically determine the different tissue types according the inherent diffusional characteristics. Seven dystonia patients with DYT1 genotype, four non-manifesting DYT1 mutation carriers and eight normal were studied.  The results show that the brain tissue can be characterized using diffusion parameters using distribution analysis in 2D.  There are considerable differences among three groups studied in terms of the parameters measured.  Our model stained the putamen a DYT1 subject suggestive of disease involvement in that area.

Bimanual Coordination and Corpus Callosum Microstructure in Young Adults with Traumatic Brain Injury
Karen Caeyenberghs¹, Alexander Leemans^2
1KULeuven, Leuven, Heverlee, Belgium; ²University Medical Center Utrecht, Netherlands

Deterioration of motor function is one of several clinical manifestations following traumatic brain injury (TBI). The aim of this study was to investigate the relationship between white matter (WM) integrity using diffusion tensor imaging (DTI) and bimanual motor performance in young TBI patients. A group suffering from moderate to severe TBI (N=25) and a control group (N=18) were scanned using DTI along with standard anatomical scans. Using ExploreDTI software, three corpus callosum subregions were evaluated. Bimanual performance was assessed using a motor switching task. This study provides evidence for a structural alteration of corpus callosum subregions in young adults with TBI that are correlated with motor functioning, inspiring new avenues for therapy.

DTI in Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Elevated Lactate (LBSL): Local Strongly Increased FA and Reduced Diffusivity  as Well as Globally Reduced FA and Increased Diffusivity
Marjan Steenweg¹, Marjo van der Knaap, Frederik Barkhof², Petra Pouwels^3
1Child Neurology, VU University Medical Center, Amsterdam, Netherlands; ²Radiology, VU University Medical Center Amsterdam, Netherlands;  ³Physics & Medical Technology, VU University Medical Center, Amsterdam, Netherlands

LBSL is an inherited white matter (WM) disorder without known pathological basis. To gain insight into tissue microstructure, this study used high-resolution DTI (1.45x1.45x2mm) at 1.5T. Performing TBSS, a general increase in MD and decrease in FA was seen in the central cerebral WM, not always coinciding with signal abnormalities on conventional images. Strikingly, ROI-analysis showed small areas with an extremely low MD, together with low axial and radial diffusivity, and very high FA. Restricted diffusion has been described in leukoencephalopathies caused by myelin vacuolation, raising the question whether this also plays a role in LBSL.

7T DTI in Mild Chronic Traumatic Brain Injury: Assessment of the Superior Longitudinal Fasciculus and Cingulum Bundle
Dustin Cunningham¹, Seongjin Choi¹, John Corrigan², Jennifer Bogner², W Mysiw², Cherian Renil Zachariah¹, Michael V. Knopp¹, Petra Schmalbrock^1
1Radiology, The Ohio State University, Columbus, OH, United States; ²Physical Medicine and Rehab, The Ohio State University, Columbus, OH, United States

In order to differentiate mild chronic traumatic brain injury (TBI) patients from age matched healthy controls we explored the use of 7T diffusion tensor imaging (DTI) of the cingulum bundle (CB) and the superior longitudinal fasciculus (SLF). We observed qualitative and quantitative differences between the two groups that included statistically different fractional anisotropy (FA) values for a ROI placed in the CB and visually different fibers for the SLF in the right hemisphere of TBI patients. Our results are encouraging because they support the idea that DTI may be useful as a tool to diagnose and characterize mild chronic TBI.

Functional and Structural Connectivity of Default Mode Network in Patients with Schizophrenia: A Combined Resting-State FMRI and Diffusion Spectrum Imaging Study
Su-Chun Huang¹, Fang-Chen Yeh^2,3, Hai-Go Hwu⁴, Chih-Min Liu⁴, Chen-Chung Liu⁴, Fa-Hsuan Lin⁵, Wen-Yih Isaac Tseng, ^2,5
1Institution of Medical Engineering, Taipei, Taiwan; ²National Taiwan University College of Medicine, Center for Optoelectronic Biomedicine, Taipei, Taiwan; ³Carnegie Mellon University , Department of Biomedical Engineering, Pittsburgh, PA, United States; ⁴National Taiwan University Hospital, Department of Psychiatry, Taipei, Taiwan; ⁵National Taiwan University, Institute of Biomedical Engineering, Taipei, Taiwan

With the combination of resting-state fMRI and DSI, the relationships between FC, SC and clinical PNASS scores were investigated in patients with schizophrenia. Significant correlations between FC and PNASS scores were found in three pairs of DMN, namely the IPL-IPR, the IPL-PCCR, and the IPR-PCCL pairs. However, the SC showed no significant correlation with PNASS score. Our results suggest that FC of DMN associates with the severity of the clinical symptoms more strongly than SC. Moreover, after ignoring three drug-naïve patients, the SC between IPR and PCCL was negatively correlated with FC, implying that alteration of FC might down regulate SC. To clarify this, a longitudinal study is warranted to study the interactions between FC and SC, and their effects on clinical symptoms during the disease course.

Automated Tract-Specific Quantification Using Probabilistic Atlas Based on Large Deformation Diffeomorphic Metric Mapping and Its Application to Alzheimer's Disease
Kegang Hua¹, Kenichi Oishi¹, Hangyi Jiang¹, Xin Li¹, Jiangyang Zhang¹, Kazi Dilruba Akhter^1,2, Michael I. Miller^3,4, Van Zijl C.M. Peter^1,5, Marilyn Albert⁶, Constantine G. Lyketsos⁷, Michelle M. Mielke⁷, Susumu Mori^1,2
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; ³Center for Imaging Science, Johns Hopkins University, Baltimore, MD, United States; ⁴Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD, United States; ⁵F.M. Kirby Research Center for Functional Brain Imaging , Kennedy Krieger Institute, Baltimore, MD, United States; ⁶Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; ⁷Department of Psychiatry, Johns Hopkins Bayview Medical Center, Baltimore, MD, United States

Tractography is widely used to define locations of specific tracts in the white matter and perform tract-specific quantification of various MR parameters such as FA and MD. However, tractography requires placements of ROIs to extract tracts of interest, which involves subjective and expert judgment. In this presentation, an automated tract-specific quantification approach is demonstrated based on pre-defined population-averaged tract information and a highly non-linear image transformation technique. This tool was applied to an Alzheimer’s disease population and age-matched control. The results show accurate tract identification and consistent diffusivity abnormality of the forceps major.