Diffusion Tensor Imaging in Psychiatry

Transcription

1 2003 KHBM DTI in Psychiatry Diffusion Tensor Imaging in Psychiatry KHBM 서울대학교 의과대학 정신과학교실 권준수

2 Neuropsychiatric conditions DTI has been studied in Alzheimer s disease Schizophrenia Alcoholism HIV infection Others Geriatric depression Parkinson s disease Dyslexia

3 Rationale for DTI in Psychiatry Brain disorders loss of brain tissue abnormal brain structures abnormal activation in functional studies Symptom formation or cognitive dysfunction connectivity abnormalities Neurodevelopmental or neurodegenerative model DTI can provide information on structural connectivity

4 Cortical connectedness Synaptogenesis random connections in early development post-natal overelaboration (gradual reduction of synaptic density) selective elimination of weaker connections in human complete by age 2 in sensory areas not complete until mid-adolescence in prefrontal and association areas late adolesc. to early adult myelination concentrated in the frontal and temporal lobe in adults, production = elimination

5 White Matter Development Hae-Jeong Park, PhD.

6 Schizophrenia Evidence of reduced connectivity postmortem histopathologic studies reduced spine dendrites and smaller dendritic abors in prefrontal cortex reduced synaptic products increased cortical neuronal density reduced neuropil without neuronal loss Uncinate fasciculus in a schizophrenic patient (Highley, Walker et al. 2002)

7 Schizophrenia Evidence of reduced connectivity in vivo structural imaging studies decreased cortical volume (frontal, temporal, limbic regions) Decreased gray matter concentrations in 50 schizophrenic patients compared with age- and sex-matched controls (Ha TH, Kwon JS et al, unpublished)

8 Schizophrenia Evidence of reduced connectivity functional imaging studies functional disconnection between frontal and posterior regions Prefrontal dissociation and abnormal prefrontal-parietal interaction during working memory in schizophrenia (Kim, Kwon et al. AJP 2002)

9 Schizophrenia Computer simulation (network performance) (Hoffman and McGlashan 1997) detection rates improved up to 30% pruning pruning above 35%, progressive impairment >40%, hallucinations were stimulated

10 Schizophrenia Developmentally Reduced Synaptic Connectivity Model for schizophrenia (McGlashan and Hoffman 2000)

11 DTI studies in schizophrenia Author Year Patients Region Measure Results Buchsbaum Statistical mapping RA Frontal, temporal, striatal Lim Prefrontal, temporalparietal, temporaloccipital FA All Steel prefrontal FA No difference Agartz Statistical mapping FA Splenium and occipital Foong Statistical mapping FA No difference Kubicki Uncinate fasciculus FA Loss of asymmetry Burns Uncinate, arcuate, ansterior cingulum FA Left uncinate and cingulum Wang Cerebellar peduncle FA No difference Minami Frontal, temporal, parietal, and occipital FA All Sun Prefrontal, temporal, occipital, internal capsule, corpus callosum FA Anterior cingulum Wolkin frontal FA Inferior frontal FA was correlated with (-) sx

12 Frontal area in schizophrenia (Buchsbaum, Tang et al. 1998) Decreased in schizophrenia Buchsbaum, Tang et al. (1998): statistical mapping Lim, Hedehus et al. (1999): ROI on segmented tissue Minami, Nobuhara et al. (2003): ROI on FA map Wolkin, Choi et al. (2003): ROI on T2 (b=0) image Negative results Steel, Bastin et al. (2001): ROI on (?) Foong, Symms et al. (2002): statistical mapping

13 Temporal area in schizophrenia Decreased in schizophrenia Lim, Hedehus et al. (1999): ROI on segmented tissue Minami, Nobuhara et al. (2003): ROI on FA map Burns, Job et al. (2003): statistical mapping Loss of asymmetry Kubicki, Westin et al. (2002): ROI on FA map Negative results Foong, Symms et al. (2002): statistical mapping (Kubicki, Westin et al. 2002)

14 arge fiber tracts in schizophrenia (Burns, Job et al. 2003) (Sun, Wang et al. 2003) (Wang, Sun et al. 2003)

15 Parietal/occipital area in SPR Splenium and occipital areas (Agartz, Andersson et al. 2001) (Lim, Hedehus et al. 1999) (Minami, Nobuhara et al. 2003)

16 Preliminary Results: Schizophrenia 서울대학교병원, 강북삼성병원, 한양대의공학과 t-statistics, p< uncorrected, cluster>20 voxels Controls 9, schizophrenics Significant FA reductions in both prefrontal regions controls schizophrenic both anterior cingulum corpus callosum R. internal capsule R prefrontal L prefrontal R int capsule Corpus callosum L cingulum R cingulum

17 Preliminary Results: OCD Trends of FA reductions in left anterior cingulum t-statistics, p< uncorrected, cluster>20 voxels Controls 9, OCD patients 11

18 Alcoholism neurotoxic effects of alcohol + poor nutrition neural consequences peripheral neuropathy cerebellar degeneration mamillary body destruction postmortem studies white matter tissue loss demyelination and axonal deletion reduction in genes coding for myelin components in vivo MRI studies WM volume reductions in cortical WM and corpus callosum

19 Male alcoholics (Pfefferbaum, Sullivan et al. 2000) 2003 KHBM DTI in Psychiatr Female alcoholics (Pfefferbaum and Sullivan 2002) DTI studies in Alcoholism FA and Coherence was compared in two studies

20 Geriatric Depression increased WM hyperintensities (WMH) in MRI associated regions increased lesion density in medial orbital prefrontal prefrontal, anterior cingulate, amygdala, striatum in functional studies neuropathology altered neuronal and glial cell morphology and density in frontal cortex treatment response executive functions integrity of fronto-striatal structure?

21 DTI in Geriatric Psychiatry One regular article and a brief report WM tract disruption in WMH (Taylor, Payne 2001) Frontal FA and treatment response (Alexopoulos, Kiosses 2002) WMH and anisotropy higher ADC and lower anisotropy a trend toward lower anisotropy in patients, left frontal Frontal WM and treatment response aim: fronto-striatal connectivity FA 15mm above AC-PC plane in left and right was associated with remission rate

22 Alzheimer s s disease progressive neurodegenerative disease medial temporal temporal, parietal neocortex WM macrostructure reductions corpus callosum, central WM suggestive of Wallerian degeneration early detection with DTI? DTI studies FA decreased in temporal, anterior and posterior cingulate, posterior corpus callusom (Takahashi, Yonezawa et al. 2002)

23 DTI in Early Alzheimer s s disease decreased lattice index in splenium, superior longitudinal fasciculus, in mild AD (Rose, Chen et al. 2000) increased ADC in hippocampus in mild cognitive impairment (Kantarci, Jack et al. 2001)

24 HIV-1 1 Infection HIV-1 enters CNS during early stage of infection infected macrophages invade WM of cerebral hemisphere, corpus callosum, and internal capsule neuropathology: diffuse WM pallor (later stage) DTI studies diffusion anisotropy in genu and splenium in intermediate and high viral loads (Filippi, Ulung et al. 2001) (Pomara, Crandall et al. 2001)

25 Methods in Psychiatric Research ROI approach manual placement of ROI on B0 image or FA map tissue segmentations and coregistration automatic voxel counting and maximum anisotropy voxel Statistical mapping whole white matter analysis small volume (combined with ROI approach)

26 Summary despite some inconsistent findings overall FA decreased in schizophrenia DTI may become of importance in psychiatric research and practice in the future with improved spatial resolution standardized analyzing methods complementary techniques like MTI (magnetic transfer imaging) and T2 relaxography applicable to many neuropsychiatric conditions developmental disorders (autism, OCD etc)

27 New Approach FA MTR Anatomical location Talairach coordinates x, y, z and corresponding Talairach coordinates x, y, z and corresponding z-score FAI z-score MTR Left frontal white matter (3.56) (3.35) Right frontal white matter (2.75) (2.29) Left internal capsule (3.77) (2.09) Right internal capsule (2.85) (3.13) Corpus Callosum (genu) (2.43) NC > SZ Corpus Callosum (body) Arcuate fasciculus? (2.32) (4.05) (Kubicki, Park)

28 New Approach Asymmetry mapping (Park 2003)

29 (Park 2003) New Approach Combination with gray matter parcellations

30 New Approach (Park 2003)

31 2003 KHBM DTI in Psychiatry 감사합니다