Diffusion Tractography of the Fornix in Male Schizophrenic Patients Background: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provide a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix anisotropy in schizophrenia. Methods: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were manually drawn to guide tractography, and Fractional Anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. Results: Analysis of variance was performed, with side as within subject factor, and group as a between subject factor, and findings demonstrated a group effect (P=0.006) for fornix FA. Post-hoc independent sample t-tests demonstrated bilateral FA decrease in schizophrenia, compared to control subjects (left side: P=0.048; right side P=0.006). Conclusions: Our investigation shows the utility of applying imaging tools, such as DTI and tractography, to study white matter fiber tracts in vivo. Our results point to bilateral disruption in the fornix integrity in schizophrenia, broadening our understanding of the pathophysiology of this disease. White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provide a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix anisotropy in schizophrenia. ABSTRACT BACKGROUND FORNIX ANATOMY RESULTS CONCLUSIONS REFERENCES 53 Fitzsimmons J 1, Kubicki M 1,2, Smith K 1, San Jose R 3, Westin CF 3, Kikinis R 3, McCarley R 2, Shenton M. 1,2,3 Fig 2: Fornix sagittal view The fibers begin in the hippocampus on each side of the brain, the separate left and right side are each called the crux of the fornix. The bundles of fibers come together in the midline of the brain, forming the body of the fornix. METHODS Subjects: DTI images were used to evaluated the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socio-economic status, and handedness. ROI placement: Regions of interest were drawn manually to guide tractography to bilaterally tract the fornix from the crux through its posterior aspects. Through the regions of interests we guide tractography, and Fractional Anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. DTI acquisition: images were acquired on a 1.5 Tesla system using a Line Scan Diffusion MR imaging technique. 35 coronal, 5mm slice thickness, 128x128 scan resolution, 6 independent directions, 1 NEX. TE (echo time) 70 ms, TR (repetition time) 80ms, effective TR 2500 ms Sensitivity tool: The goal of using this tool is to eliminate the fibers with a low degree of inclusion on the selected ROI. Our results point to bilateral disruption in the fornix integrity in schizophrenia. Considering the role of the fornix in connecting key brain structures involved in superior cognitive functions, this study can help broaden our understanding of the pathophysiology of this disease. DTI and tractography has proven as an imaging useful tool to study white matter fiber tracts in vivo. Fig 3.1: First ROI in coronal planeFig 3.2: Coronal view of left and right ROI Fig3.3: Sagittal view of the fibers passing through the 5 ROI’s Fig 1 : Fornix scheme 1.Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. 2.Department of Psychiatry, VA Boston healthcare System, Harvard Medical School, Boston, MA. 3.Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. 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