Diffusion Tractography of the Fornix in Male Schizophrenic Patients Background: White matter fiber...
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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 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 www.sci.uidaho.edu/med532/ fornix.htm •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 plane Fig 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 www.benbest.com/science/anatmind/anatm d7.html 1. 1. Psychiatry Neuroimaging Laboratory , Department of Psychiatry, Brigham and Women’s Hospital, Psychiatry Neuroimaging Laboratory , Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Harvard Medical School, Boston, MA. 2. 2. Department of Psychiatry, VA Boston healthcare System, Harvard Medical School, Boston, MA. Department of Psychiatry, VA Boston healthcare System, Harvard Medical School, Boston, MA. 3. 3. Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Hospital, Harvard Medical School, Boston, MA. Controls n=35 Schizophrenic s n=36 - 100% 100% Handedness (%right) 0.278 2.75 (1.34) 3.06 (.983) PSES 0.897 39.59 (9.32) 39.89 (9.06) Age - 100% 100% Sex (%male) p value Mean (standard deviation) P value Effect 0.006 Group 0.269 Side x group 0.054 Side ANOVA FA 0.006 FA Right 0.048 FA Left T Test (between groups) P = 0.510 SZ R = L P = 0.055 Controls R > L T Test (within groups) Calabrese P, Markowitsch HJ, Harders AG, Scholz M, Gehlen W (1995): Fornix damage and memory: Calabrese P, Markowitsch HJ, Harders AG, Scholz M, Gehlen W (1995): Fornix damage and memory: A case report. A case report. Cortex 31 Cortex 31 :555-64. :555-64. Chance SA, Highley JR, Esiri MM, Crow TJ (1999): Fiber content of the fornix in Chance SA, Highley JR, Esiri MM, Crow TJ (1999): Fiber content of the fornix in schizophrenia: lack of evidence for a primary limbic encephalopathy. schizophrenia: lack of evidence for a primary limbic encephalopathy. Am J Psychiatry 156: Am J Psychiatry 156: 1720-4. 1720-4. Dusek JA, Eichenbaum H (1997): The hippocampus and memory for orderly stimulus relations. Dusek JA, Eichenbaum H (1997): The hippocampus and memory for orderly stimulus relations. Proc Natl Acad Sci U S A 94 Proc Natl Acad Sci U S A 94 :7109-14. :7109-14. Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ (1994): Event-related Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ (1994): Event-related potential abnormalities correlate with structural brain alterations and clinical features in potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia. patients with chronic schizophrenia. Schizophr Res 11 Schizophr Res 11 :259-71. :259-71. Gaffan D (1994): Dissociated effects of perirhinal cortex ablation, fornix transection and Gaffan D (1994): Dissociated effects of perirhinal cortex ablation, fornix transection and amygdalectomy: evidence for multiple memory systems in the primate temporal lobe. amygdalectomy: evidence for multiple memory systems in the primate temporal lobe. Exp Brain Res Exp Brain Res 99 99 :411-22. :411-22. Gaffan D, Harrison S (1989): Place memory and scene memory: effects of fornix transection in Gaffan D, Harrison S (1989): Place memory and scene memory: effects of fornix transection in the monkey. the monkey. Exp Brain Res 74 Exp Brain Res 74 :202-12. :202-12. Kuroki N, Kubicki M, Nestor PG, et al (2006): Fornix integrity and hippocampal volume in Kuroki N, Kubicki M, Nestor PG, et al (2006): Fornix integrity and hippocampal volume in male schizophrenic patients. male schizophrenic patients. Biol Psychiatry 60 Biol Psychiatry 60 :22-31. :22-31. Zahajszky J, Dickey CC, McCarley RW, et al (2001): A quantitative MR measure of the fornix Zahajszky J, Dickey CC, McCarley RW, et al (2001): A quantitative MR measure of the fornix in schizophrenia. in schizophrenia. Schizophr Res 47 Schizophr Res 47 :87-97 :87-97. Fig 3.4: Tracts with ROIs Mean FA
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Transcript of Diffusion Tractography of the Fornix in Male Schizophrenic Patients Background: White matter fiber...
Diffusion Tractography of the Fornix in Male Schizophrenic PatientsDiffusion 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
CONCLUSIONSREFERENCES
5353
Fitzsimmons J1, Kubicki M1,2, Smith K1, San Jose R3, Westin CF3, Kikinis R3, McCarley R2, Shenton M.1,2,3
Fig 2: Fornix sagittal viewwww.sci.uidaho.edu/med532/fornix.htm
•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 plane Fig 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 www.benbest.com/science/anatmind/anatmd7.html
1.1. Psychiatry Neuroimaging Laboratory , Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Psychiatry Neuroimaging Laboratory , Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Boston, MA.
2.2. Department of Psychiatry, VA Boston healthcare System, Harvard Medical School, Boston, MA.Department of Psychiatry, VA Boston healthcare System, Harvard Medical School, Boston, MA.
3.3. Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Boston, MA.
Controls
n=35
Schizophrenics
n=36
- 100% 100%Handedness (%right)
0.278 2.75 (1.34) 3.06 (.983)PSES
0.897 39.59 (9.32) 39.89 (9.06)Age
- 100% 100%Sex (%male)
p value
Mean (standard deviation)
P valueEffect
0.006Group
0.269Side x group
0.054Side
ANOVA FA
0.006FA Right
0.048FA Left
T Test (between groups)
P = 0.510SZ
R = L
P = 0.055Controls
R > L
T Test (within groups)
Calabrese P, Markowitsch HJ, Harders AG, Scholz M, Gehlen W (1995): Fornix damage and memory: A case report.Calabrese P, Markowitsch HJ, Harders AG, Scholz M, Gehlen W (1995): Fornix damage and memory: A case report. Cortex Cortex 3131:555-64.:555-64.
Chance SA, Highley JR, Esiri MM, Crow TJ (1999): Fiber content of the fornix in schizophrenia: lack of evidence for a primary Chance SA, Highley JR, Esiri MM, Crow TJ (1999): Fiber content of the fornix in schizophrenia: lack of evidence for a primary limbic encephalopathy. limbic encephalopathy. Am J Psychiatry 156:Am J Psychiatry 156:1720-4.1720-4.
Dusek JA, Eichenbaum H (1997): The hippocampus and memory for orderly stimulus relations. Dusek JA, Eichenbaum H (1997): The hippocampus and memory for orderly stimulus relations. Proc Natl Acad Sci U S A Proc Natl Acad Sci U S A 9494:7109-14.:7109-14.
Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ (1994): Event-related potential abnormalities correlate Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ (1994): Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia. with structural brain alterations and clinical features in patients with chronic schizophrenia. Schizophr Res 11Schizophr Res 11:259-71.:259-71.
Gaffan D (1994): Dissociated effects of perirhinal cortex ablation, fornix transection and amygdalectomy: evidence for multiple Gaffan D (1994): Dissociated effects of perirhinal cortex ablation, fornix transection and amygdalectomy: evidence for multiple memory systems in the primate temporal lobe. memory systems in the primate temporal lobe. Exp Brain Res 99Exp Brain Res 99:411-22.:411-22.
Gaffan D, Harrison S (1989): Place memory and scene memory: effects of fornix transection in the monkey. Gaffan D, Harrison S (1989): Place memory and scene memory: effects of fornix transection in the monkey. Exp Brain Res 74Exp Brain Res 74:202-:202-12.12.
Kuroki N, Kubicki M, Nestor PG, et al (2006): Fornix integrity and hippocampal volume in male schizophrenic patients. Kuroki N, Kubicki M, Nestor PG, et al (2006): Fornix integrity and hippocampal volume in male schizophrenic patients. Biol Biol Psychiatry 60Psychiatry 60:22-31.:22-31.
Zahajszky J, Dickey CC, McCarley RW, et al (2001): A quantitative MR measure of the fornix in schizophrenia. Zahajszky J, Dickey CC, McCarley RW, et al (2001): A quantitative MR measure of the fornix in schizophrenia. Schizophr Res Schizophr Res 4747:87-97:87-97..
Fig 3.4: Tracts with ROIs
Mea
n F
A
