Clinical Implication of Multimodal Neuroimaging

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Clinical Implication of Multimodal Neuroimaging

• Jungsu S. Oh, Ph.D.
• Assistant Professor
• BK21 Division of Human Life Science
• Seoul National University

On behalf of Jun Soo Kwon, M.D., Ph.D. (Clinical
Neuroscience and Computational Neuroscience
Unit) Professor at BCS, Seoul National University
WCU
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Background

• Interests in brain function and connectivity have
  much grown up in recent decades.
• Synergic effects of Multi-modal/Multi-technique
  Imaging, which is useful
• not only for assessing chronic patients
• but also for detecting subtle changes in
• Ultra-high-risk (UHR) pathological subjects
• Neuro-plasticity groups

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Example of High-risk group in the course of
schizophrenia
Healthy ? ? Severity of Symptoms
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Basic Structures of Brain

• Gray Matter
• Functional activations
• Structural imaging
• Functional/molecular imaging
• White Matter (Tracts)
• Connecting distinctive functional regions
• Diffusion Tensor MRI for reconstructing pathway
  information and estimating quantity/quality of
  anatomical connectivity

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Basic Principle and Properties of Diffusion
Tensor Imaging (DTI)

• Mean Diffusivity (Dm)
• Size of tensor
• (Degree of tissue microstructure disruption)
• Fractional Anisotropy (FA)
• Sharpness of tensor
• Normalized variance of eigenvalues01
• (Degree of fiber integrity)
• Mode (Ennis and Kindlmann, MRM, 2006)
• Proximity of tensor shape to a disc
• Degree of fiber crossing
• two principal axes disc shape
• Negative Mode
• Crossing fiber tracts ?1 ?2 gt ?3

gt
gt
Free Water Isotropic Diffusion
White Matter Tracts Anisotropic Diffusion
?1 ?2 gt ?3
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Tract (Tractography)-Based DTI Analysis

• Not only diffusion properties but connectivity
• Not only visualization tool but quantitative
  analysis tool of fiber tracts
• Tractography Methods
• Most Basic Streamline
• Using principal diffusion direction(e1) only
• Euler Integration method
• Tensorline (regularized, using tensor
  deflection), level set-based tractography (fast
  marching tractography)
• High-End Stochastic Tractography and High
  Angular Resolution Diffusion Imaging (DSI, QBI)

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Quantitative DTI analysis using Brodmann
ROI-based parcellation and tract parameterization
Application in Drug-naïve OCD patients
Shape-based parameterization
(Oh et al., NeuroImage, 2007)
(Oh et al., Unpublished data)
Application in UHR Schizophrenia patients
?
(Oh et al., in preparation)
(Oh et al., Human Brain Mapping, in press)
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Functional imaging-based estimation of functional
activation and connectivity
Magnetoencephalogram (MEG)
Resting-state fMRI

• Decreased desynchronization of alpha rhythm in
  UHR
• Deficits of top-down inhibitory control

(Koh et al., Unpublished data)

• Deficits of early stage of auditory processing in
  UHR
• N1m and MMNm dipole moments may represent a
  vulnerability marker in evaluating the risk of
  transition to psychotic stage in UHR group.

(Oh et al., Annual Meeting of Biol Psychiatry
2008)
(Shin et al., Biol Psychiatry, in press)
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Synergic Effects of Multi-modal/Multi-technique
Imaging
Connectivity
Structure
Function
Brain Imaging
IT
BT
Biomarker
To Better Understand the Etiology of SZ/ OCD/
To Better Detect High-Risk Groups for SZ/ OCD/
Genetics Study
BT
NT
Abbreviations SZ Schizophrenia OCD
Obsessive-Compulsive Disorder
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Future Directions of High Risk Study
Large sample size and longitudinal study
Prerequisites

• Effective strategies for the recruitment of
  high-risk groups
• Continuous efforts for the follow-up studies

Combinational approach of structural and
functional imaging
Functional imaging-based connectivity

• Temporal activation in fMRI/MEG
• Intersubject variability of FDG PET

Structural imaging-based connectivity

• Mostly, DTI tractography-based approach

Structural Shape

• Cortical thickness, CC shape, Basal ganglia shape

Genetics-neuroimaging integration
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An exemplary study of neuro-plasticity groups
the Baduk (Go) game experts
Working memory task-related fMRI
Voxel-based DTI analysis
(Park et al., Unpublished data)
(Lee et al., Unpublished data)
Integrated Anatomo-Functional Connectivity
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Conclusion

• Multimodal neuroimaging including structural,
  functional and genetic imaging will add to
• finding biomarkers to detect subtle changes in
  high risk groups
• facilliating the development of treatment and
  precaution strategies of psychiatric disorders.
• Its application for assessing neuro-plasticity
  groups (e.g., extraordinary IQ, meditation, Baduk
  experts) looks promising as well.

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Seoul Youth Clinic (SYC)

• Brief history of SYC

• Procedures in SYC

• Started SYC in 16 June, 2004
• Recruited 103 subjects of CHR/GHR SZ
  
• - 12 subjects conversion to psychosis (CHR
  only)
• - 18 subjects drop-up
• - 73 subjects follow-up
• Mediation Among the CHR groups, 36 subjects have
  been taken for antipsychotics.
• Related publications
• - Potential vulnerability markers within the
  affective domain in subjects at genetic and
  clinical high risk for schizophrenia.
  Psychopathology. 2008, Apr
• - Deficit of theory of mind in individuals at
  ultra-high-risk for schizophrenia. Schizophr Res.
  2008, Feb
• - Pre-attentive auditory processing in
  ultra-high-risk for schizophrenia with
  magnetoencephalography. Biol Psychiatry, in press