Diffusion Tensor Imaging in Psychiatry · 2016. 9. 21. · 2003 KHBM DTI in Psychiatry Cortical connectedness zSynaptogenesis 9random connections in early development 9post-natal

2003 KHBM DTI in Psychiatry

Diffusion TensorDiffusion Tensor ImagingImaging

in Psychiatryin PsychiatryKHBM 2003. 11. 21.

서울대학교 의과대학

정신과학교실

권 준 수


NeuropsychiatricNeuropsychiatric conditionsconditions

DTI has been studied inAlzheimer’s diseaseSchizophreniaAlcoholismHIV infectionOthers

► Geriatric depression► Parkinson’s disease► Dyslexia


Rationale for DTI in PsychiatryRationale for DTI in Psychiatry

Brain disordersloss of brain tissueabnormal brain structuresabnormal activation in functional studies

Symptom formation or cognitive dysfunctionconnectivity abnormalities

Neurodevelopmental or neurodegenerative model

DTI can provide information on structural connectivity


Cortical connectednessCortical connectedness

Synaptogenesisrandom connections in early developmentpost-natal overelaboration (gradual reduction of synaptic density)

► selective elimination of weaker connectionsin 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


White Matter DevelopmentWhite Matter Development

Hae-Jeong Park, PhD.


SchizophreniaSchizophrenia

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)



Evidence of reduced connectivityin 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matter concentrations in 50 schizophrenic patients compared with age- and sex-matched controls (Ha TH, Kwon JS et al, unpublished)



Evidence of reduced connectivityfunctional 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)



Computer simulation (network performance)(Hoffman and McGlashan 1997)

detection rates improved up to 30% pruning

pruning above 35%, progressive impairment

>40%, hallucinations were stimulated



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


DTI studies in schizophreniaDTI studies in schizophrenia

Anterior cingulum ↓FAPrefrontal, temporal, occipital, internal capsule, corpus callosum

302003Sun

Inferior frontal FA was correlated with (-) sx

FAfrontal102003Wolkin

All ↓FAFrontal, temporal, parietal, and occipital

122003Minami

No differenceFACerebellar peduncle292003Wang

Left uncinate and cingulum↓

FAUncinate, arcuate, ansterior cingulum

302003Burns

Loss of asymmetryFAUncinate fasciculus152002Kubicki

No differenceFAStatistical mapping142002Foong

Splenium and occipital ↓FAStatistical mapping202001Agartz

No differenceFAprefrontal102001Steel

All ↓FAPrefrontal, temporal-parietal, temporal-occipital

101999Lim

Frontal, temporal, striatal ↓RAStatistical mapping51998Buchsbaum

ResultsMeasureRegionPatientsYearAuthor


Frontal area in schizophreniaFrontal area in schizophrenia

(Buchsbaum, Tang et al. 1998)

Decreased in schizophreniaBuchsbaum, Tang et al. (1998): statistical mappingLim, Hedehus et al. (1999): ROI on segmented tissueMinami, Nobuhara et al. (2003): ROI on FA mapWolkin, Choi et al. (2003): ROI on T2 (b=0) image

Negative resultsSteel, Bastin et al. (2001): ROI on (?)Foong, Symms et al. (2002): statistical mapping


Temporal area in schizophreniaTemporal area in schizophrenia

Decreased in schizophreniaLim, Hedehus et al. (1999): ROI on segmented tissueMinami, Nobuhara et al. (2003): ROI on FA mapBurns, Job et al. (2003): statistical mapping

Loss of asymmetryKubicki, Westin et al. (2002): ROI on FA map

Negative resultsFoong, Symms et al. (2002): statistical mapping

(Kubicki, Westin et al. 2002)


Large fiber tracts in schizophreniaLarge fiber tracts in schizophrenia

(Burns, Job et al. 2003)

(Wang, Sun et al. 2003)

(Sun, Wang et al. 2003)


Parietal/occipital area in SPRParietal/occipital area in SPR

Splenium and occipital areas(Agartz, Andersson et al. 2001)

(Lim, Hedehus et al. 1999)(Minami, Nobuhara et al. 2003)


Preliminary Results: Schizophrenia Preliminary Results: Schizophrenia 서울대학교병원서울대학교병원, , 강북삼성병원강북삼성병원, , 한양대의공학과한양대의공학과

t-statistics, p<0.0005 uncorrected, cluster>20 voxels

Controls 9, schizophrenics 6

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controlsschizophrenics

Significant FA reductions in• both prefrontal regions

• both anterior cingulum

• corpus callosum

• R. internal capsule


Preliminary Results: OCDPreliminary Results: OCD

t-statistics, p<0.0025 uncorrected, cluster>20 voxels

Controls 9, OCD patients 11

Trends of FA reductions in• left anterior cingulum


AlcoholismAlcoholism

neurotoxic effects of alcohol + poor nutritionneural 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


DTI studies in AlcoholismDTI studies in AlcoholismFAFA and CoherenceCoherence was compared in two studies

Male alcoholics(Pfefferbaum, Sullivan et al. 2000)

Female alcoholics(Pfefferbaum and Sullivan 2002)


Geriatric DepressionGeriatric Depression

increased WM hyperintensities (WMH) in MRIassociated regions

increased lesion density in medial orbital prefrontalprefrontal, anterior cingulate, amygdala, striatum in functional studies

neuropathologyaltered neuronal and glial cell morphology and density in frontal cortex

treatment responseexecutive functionsintegrity of fronto-striatal structure?


DTI in Geriatric PsychiatryDTI in Geriatric Psychiatry

One regular article and a brief reportWM tract disruption in WMH (Taylor, Payne 2001)

Frontal FA and treatment response (Alexopoulos, Kiosses 2002)

WMH and anisotropyhigher ADC and lower anisotropya trend toward lower anisotropy in patients, left frontal

Frontal WM and treatment responseaim: fronto-striatal connectivityFA 15mm above AC-PC plane in left and right was associated with remission rate


AlzheimerAlzheimer’’s diseases disease

progressive neurodegenerative diseasemedial temporal → temporal, parietal neocortexWM macrostructure reductions

corpus callosum, central WMsuggestive of Wallerian degenerationearly detection with DTI ?

DTI studies

FA decreased in temporal, anterior and posterior cingulate, posterior corpus callusom

(Takahashi, Yonezawa et al. 2002)


DTI in Early AlzheimerDTI in Early Alzheimer’’s diseases 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)


HIVHIV--1 Infection1 Infection

HIV-1 enters CNS during early stage of infectioninfected macrophages invade WM of cerebral hemisphere, corpus callosum, and internal capsuleneuropathology: 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)


Methods in Psychiatric ResearchMethods in Psychiatric ResearchROI approach

manual placement of ROIon B0 image or FA map

automatic voxel counting and maximum anisotropy voxel

tissue segmentations and coregistration

Statistical mappingwhole white matter analysis

small volume (combined with ROI approach)


SummarySummary

despite some inconsistent findingsoverall FA decreased in schizophreniaDTI may become of importance in psychiatric research and practice in the future with

improved spatial resolutionstandardized analyzing methodscomplementary techniques like MTI (magnetic transfer imaging) and T2 relaxography

applicable to many neuropsychiatric conditionsdevelopmental disorders (autism, OCD etc)


New ApproachNew Approach

-31 -51 40 (4.05)Arcuate fasciculus?

-4 32 4 (2.32)Corpus Callosum(body)

-4 7 24 (2.43)Corpus Callosum(genu)

-15 8 2 (3.13)23 14 14 (2.85) Right internal capsule

14 -3 10 (2.09)-24 11 13 (3.77)Left internal capsule

25 31 24 (2.29)33 44 8 (2.75)Right frontal white matter

-12 39 30 (3.35)-28 44 11 (3.56)Left frontal white matter

Talairach coordinatesx, y, z and

corresponding z-scoreMTR

Talairach coordinatesx, y, z and

corresponding z-score

FAI

Anatomical locationFA MTR

NC > SZ(Kubicki, Park)



(Park 2003)

Asymmetry mapping


New ApproachNew ApproachCombination with gray matter parcellations

(Park 2003)


(Park 2003)



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Documents

Diffusion Tensor Imaging in Psychiatry · 2016. 9. 21. · 2003 KHBM DTI in Psychiatry Cortical connectedness zSynaptogenesis 9random connections in early development 9post-natal