Alterations: A Diffusion Tensor Imaging Study.

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Alterations: A Diffusion Tensor Imaging Study. Brain Injury in Battered Women and Its Relationship to Microstructural White Matter Alterations: A Diffusion Tensor Imaging Study. 0339 Eve M. Valera, (1), Alan N. Francis, (1), Zhi Li (1), Nikos Makris (1), Ezra Wegbreit (2), Margaret O'Connor (3). (1) Harvard Medical School/Massachusetts General Hospital, MA, USA (2) Brown University Medical School Department of Psychiatry/Bradley Hospital, RI, USA (3) Harvard Medical School/Beth Israel Deaconess Medical Center, MA, USA ABSTRACT RESULTS Significantly decreased fractional anisotropy (FA) in the BW2 in comparison with the BW1 group in the splenium, right posterior corona radiata, right superior corona radiata and right cortico-spinal tract (P = 0.05; corrected for multiple comparisons). FA of the splenium [r = -.56 p < 0.006], right superior corona radiata [r = -.46 p < 0.03] and right cortico-spinal tract [r = -.58 p < 0.004] negatively correlated with the number of mTBIs. We examined correlations between the FA of the regions above with the following cognitive variables: Executive function, Processing Speed, variables from the Continuous Perfromance Test, and the California Verbal Learning test. We found that FA in the right superior corona radiata correlated positively with learning on the CVLT -2 ss learning z Sum (r = .48 p < 0.022), R Superior Corona Radiata FA against CPT InATN-hitRT neg-Z [r = .52 p < 0.01], R. Cortico - Spinal Tract FA against CPT - InATN-hitRT neg-Z [r = .51 p < 0.013] Callosal Body FA against CPT - InATN-hitRT neg-Z [r = .47 p < 0.02], R. Superior Corona Radiata FA against CPT - InATN-var neg Z: [r = .47 p < 0.02], Superior Corona Radiata against CVLT-ss_tr5 Sum Z: [r = .52 p < 0.01] FreeSurfer – TRACULA analysis: Based on the study hypotheses, we examined 4 tracts bilaterally. 1. Cortico-spinal Tract 2. Forceps Major 3. Forceps Minor 4. Anterior Thalamic Radiation. 1. We found significantly decreased Axial Diffusivity (avg) in the Left Cortico-spinal Tract (p < 0.018) and Left anterior Thalamic Radiation (p < 0.05) in the women with greater MTBI, while the R Cortico-spinal tract showed a trend in the same direction. 2. We found that the Brain Injury (BI) score was negatively correlated with Left CST AD [r = -.57; p < 0.004] in the combined groups. 3. There were no significant DTI - Cognition correlations. Analysis of Superior Longitudinal Fascicle - Parietal and Temporal 1. Analysis of bilateral SLF - parietal left and right [FA, AD, RD and MD and Trace]. No significant differences between the groups were detected. 2. Analysis of the bilateral SLF -Temporal. We examined FA ,AD, RD, MD and TRACE. Significant FA differences were found in the SLF T. Left FA - p < 0.01; Right FA p < 0.002. and a trend in left AD [p < 0.09]. Cortical Thickness analysis: The SLF-P interconnects regions such as caudal and rostral Middle PFC (DLPFC), and Supramarginal gyrus and angular gyrus (IPC). The SLF_T interconnects the STG with the inferior frontal gyrus. The left Superior temporal Gyrus thickness was significantly different between the groups at p < 0.02. The right STG was trending at p < 0.06. Cortical Thickness correlated with measures of cognition. R STG & Executive function r = .40 p < 0.05, R STG & Proc Speed r = .38 p < 0.07, R. STG & CPT INT r = .54 p < 0.007 , R STG and CPT VIG r = .55 p < 0.006, Left STG Thickness was also correlated with BI Score, Left STG & BI Score r = -.55 p < 0.007. We also correlated the structural ROIs mentioned above with the same Z scored cognitive measures. The SLF- P thickness was significantly correlated with Left Supra Marginal Gyrus & CPT INT r = .46 p < 0.029 , CVLT2 & Caudal Mid Frontal r = .39 p < 0.06, R. Rostral Mid Frontal & BI Score r = .45 p < 0.03, R Supra Marginal Gyrus & CPT INT r = .44 p < 0.03. The R inferior parietal was correlated with Exec Function r = -.45 p < 0.03 , CVLT2_ss_Learning_Zsum r = -.44 p < 0.034, CVLT2_raw_Learning_Zsum r = -.41 p < 0.047 and a trend, CVLT2_raw_Zsum r = -.36 p < 0.08. OBJECTIVES: It is estimated that 2-4 million women are severely assaulted by partners each year. These women report a wide range of abusive acts that can cause mild traumatic brain injuries (mTBIs), that often result in the shearing and straining of axonal fibers, referred to as diffuse axonal injury (DAI). Surprisingly, almost no research exists on the effects of partner-related brain injury. In an exception, our previous work demonstrated that nearly 75% of battered women sustained partner-related brain injuries, and 50% sustained multiple partner-related brain injuries, the severity of which were associated with partner-abuse severity, cognitive functioning, and psychopathology (Valera & Berenbaum, 2003). Building on these results, we used diffusion tensor imaging (DTI) to examine the relationship between partner-related brain injuries, abnormalities in white matter integrity (possibly resulting from DAI), and cognitive functioning. METHODS: Twenty-two women with a history of being in a physically abusive relationship underwent DTI imaging, a semi-structured brain injury severity interview, and cognitive and psychological assessments. For each woman, FSL-TBSS was used to calculate fractional anisotropy (FA) maps, and to create alignment-invariant tract representations of the white matter. FA values were compared between women with a limited number of mTBIs (Group “BW1”, N=11), and women with an extensive number of mTBIs (Group “BW2”, N=11). FA values were also correlated with a brain injury severity score as well as scores from standardized tests of executive functioning, attention, memory and learning. RESULTS: DTI analysis demonstrated significantly decreased FA in the BW2 in comparison with the BW1 group in the splenium, right posterior corona radiata, right superior corona radiata and right cortico-spinal tract (p = 0.05; corrected for multiple comparisons), including the superior longitudinal fascicle II (SLF II) within these areas. FA of the callosal body (r = -.50, p = .02) and right cortico-spinal tract (r = -.41, p = .06, trend) negatively correlated with a brain injury severity score. FA in the right superior corona radiata (including SLF II) correlated positively with scores of memory and learning on the California Verbal Learning Test (r’s = .49 and .45, p’s = 0.02 and .04) and negatively with innattention and impulsivity measures on a Continuous Performance Test (r's = -.51 and -.43, p's = .02 and .04). CONCLUSIONS: To our knowledge this is the first study to use neuroimaging to examine brain injuries in battered women. We found associations between partner-related mTBIs, measures of white matter integrity, and cognitive functioning in these women. The effects of such brain injuries could contribute to the attention and concentration difficulties many battered women report. The implications of these findings on personal, social, legal and treatment issues will be discussed. Figure 1 Whole Brain Tractography showing altered FA in the Right CST, Superior Corona Radiata, Callosal Body and Anterior Thalamic Radiation STUDY HYPOTHESES In comparison with the lesser MTBI group, the greater MTBI group would show significant reductions in FA, AD in the Corpus Callosum : Genu and Splenium, The R & L Corticospinal Tract including the internal capsule. The R & L anterior thalamic radiation would be the control region. BACKGROUND CONCLUSIONS Figure 6 5 automatically clustered subdivisions of the corpus, the significantly different cluster, CC2, is highlighted in red. We demonstrate the method of anatomical division of the Corpus Callosum. Our findings suggest possible abnormalities in interhemispheric connectivity between posterior parts of the frontal lobes in chronic schizophrenia. Further studies are needed to investigate the clinical role of these abnormalities. Figure 2 The Right Cortico-Spinal Tract MATERIALS AND METHODS REFERENCES SUBJECTS: 12 Schizophrenic Patients (mean age = 44.25) and 12 Normal Controls (mean age = 40.33) Table 1 AUTOMATIC SEGMENTATION: After scans were acquired, DTI Fiber Tractography (Figure 4) was performed on the whole brain for each subject, and then using an automatic procedure, the tracts were grouped into clusters, according to a pairwise similarity function that takes into account the tracts’ shapes and spatial locations (O’Donnell, 2006). Figure 5 Five fiber clusters were defined for the Corpus Callosum. Figure 6 DTI ACQUSITION: 3 Tesla GE system (General Electric Medical Systems, Milwaukee, WI) Echo Planar Imaging (EPI) DTI Tensor sequence. Acquired 51 directions with b=700, 8 baseline scans with b=0 and a spatial resolution of 1.7 x 1.7 x 1.7 ROIs: Each voxel of the midsagittal slice was color-coded according to the cluster it belonged to. (Figure 7) Mean FA, a measure of the fraction of magnitude of the tensor associated with anisotropic diffusion (Figure 8), for each segment was calculated, and compared between groups. (Table 2) Volumes of the midsagittal segments were also measured and compared between groups. (Table 3) Alexander AL, Tsurda JS, Parker DL (1997): Elimination of eddy current artifacts in diffusion-weighted echo-planar images: the use of bipolar gradients. Magn Reson Med, 38:1016-21. Crow TJ (1998): Schizophrenia as a transcallosal misconnection syndrome. Schizophr Res 30:111-4.   Foong J, Maier M, Clark CA, Barker GJ, Miller DH, Ron MA (2000): Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 68:242-4. Heid O, Deimling M, Huk W (1995): Ultra-rapid gradient echo imaging. Magn Reson Med 33:143-9. Lent R, Schmidt SL (1993): The ontogenesis of the forebrain commissures and the determination of brain asymmetries. Prog Neurobiol 40:249-76. Mori S, Crain BJ, Chacko VP, van Zijl PC (1999): Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:265-9. O'Donnell LJ, Kubicki M, Shenton ME, Dreusicke MH, Grimson WE, Westin CF (2006): A method for clustering white matter fiber tracts. AJNR Am J Neuroradiol 27:1032-6. O'Shea RP, Corballis PM (2003): Binocular rivalry in split-brain observers. J Vis 3:610-5. Schmahmann JD, Pandya, DN (2006): Fiber Pathways of the Brain. New York: Oxford University Press. Witelson SF (1989): Hand sex differences in the isthmus and genu of the human corpus callosum. Brain 112:799-835. Woodruff PW, McManus IC, David AS (1995): Meta-analysis of corpus callosum size in schizophrenia. J Neurol Neurosurg Psychiatry 58:457-61. (Kuroki 2006) Figure 2. DTI offers a way to examine the amount of diffusivity of water inside the brain.