Use of Multimodal Neuroimaging Techniques to Examine Age ... · Age, Sex, and Alcohol-Related...
Transcript of Use of Multimodal Neuroimaging Techniques to Examine Age ... · Age, Sex, and Alcohol-Related...
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Use of Multimodal Neuroimaging Techniques to Examine Age, Sex, and Alcohol-Related Changes in Brain
Structure Through Adolescence and Young Adulthood
Adolf Pfefferbaum, M.D.Edith V. Sullivan, Ph.D.
Center for Health Sciences, SRI InternationalDepartment of Psychiatry & Behavioral Sciences, Stanford University
School of Medicine
Supported by NIH/NIAAA
American Psychiatric AssociationSan Diego, CA24 May 2017
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National Consortium on Alcohol and NeuroDevelopment in Adolescence
Prospective monitoring of brain development in 831 adolescents annually for 5 years to• determine the effects of early, heavy alcohol use on
brain structure and function before drinking onset• 647 no/low drinking• 134 exceeded criteria• Cohort sequential design
age 12-14, 15-17, 18-21 years
Oregon HSU
SRI
UC San Diego
UPitt
Duke
5 U.S. Recruitment Sites
FUNDINGNIAAA, NIDA, NIMH, NICHD
NeuroInformatics
Platform
SRI+Stanford
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Oregon HSU
SRI
UC San Diego
UPitt
Duke
5 U.S. Recruitment Sites
FUNDINGNIAAA, NIDA, NIMH, NICHD
NeuroInformatics
Platform
SRI+Stanford
Extending Analysis of Imaging Data
Cortical Myelin
Subcortical Brain Iron
Effects of Initiation of Drinking
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Structural MRIQuantitative Measures of Regional Brain Tissue
white matter
gray matter
CSF
Tissue Segmentation
Structural MRI
FreeSurfer Gray Matter Regions
FrontalParietal
TemporalOccipital
Cingulate
Subcorticalwhitematter
Corpus callosum
Pons
SRI24 White Matter Regions
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NCANDA 647 No-to-Low Drinking Sample
Sex Ethnicity
Pfefferbaum et al. Cerebral Cortex2016
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Source of Sex Difference in Cortical Measures
Age
Cortical Thickness
Cortical Volume
Age
Cortical Surface Area
Age
MaleFemale
Age
Cortical Thickness
Cortical Volume
Age
Cortical Surface Area
Age
MaleFemale
Supratentorial volume
Cortical Thickness
Cortical Volume
Supratentorial volume
Cortical Surface Area
Supratentorial volume
MaleFemale
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Age (years)
Age (years)
Regional Cortical Thickness
NCANDA CohortBaseline MRI by Age and Sex
Frontal
Temporal
BoysGirls
Pfefferbaum et al. Cerebral Cortex2016
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NeuroInformatics
Platform
Extending Analysis of Imaging DataCortical Myelin
Stiles & Jernigan Neuropsychology Review 2010
Dongjin KwonKilian Pohl
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Measuring Cortical Thicknessin No/Low Adolescents
at Baseline
Average Age 21.00
1.78 mm 3.63 mm
Average Age
12.22
Cortical Thickness
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1.78 mm 3.63 mm
Cortical thickness (mm)
4
Medial frontal
Anterior temporal
Insular
Occipital
12 year olds
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1.78 mm 3.63 mm
Cortical thickness (mm)
3
Medial frontal
Anterior temporal
Insular
Occipital
14 year olds
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1.78 mm 3.63 mm
Cortical thickness (mm)
2
Medial frontal
Anterior temporal
Insular
Occipital
16 year olds
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1.78 mm 3.63 mm
Cortical thickness (mm)
1
Medial frontal
Anterior temporal
Insular
Occipital
18 year olds
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20 year olds
Medial frontal
Anterior temporal
Insular
Occipital
01.78 mm 3.63 mm
Cortical thickness (mm)
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Compute Myelinin 226 Adolescents
at Baseline
0.04 0.96%
T1/T2 image
T1 image
T2 image
Register
motor
occipital
sensory
cingulate
Heschl
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Age-related Difference in Myelin Content
Average
0.04 0.96%April 4 2017
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Developmental Slope
-0.01 0.01% / Age
Average
0.04 0.96%
precentralgyrus
centralsulcus
SignificantAge Effect
D. Kwon et al. OHBM June 27, 2017 Vancouver, Canada
Dongjin KwonKilian Pohl
Age-related Difference in Myelin Content
motor central sulcus
posterior cingulate
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NeuroInformatics
Platform
Extending Analysis of Imaging DataSubcortical Brain Iron
Michael De BellisEric Peterson
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T2*18-21
Echo-planar Imaging (EPI) fMRI Sequence(T2* Weighted)
Globus pallidus Substantia nigra
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Substantia nigraGlobus pallidus
Cerebellar dentate
Susceptibility Weighted Imaging (SWI)(T2* Weighted)
Michael De Bellis
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Substantia nigraGlobus pallidus
Cerebellar dentate
Spin-echo Diffusion Tensor Imaging (DTI)(T2 Weighted)
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Hallgren and Sourander, Journal of Neurochemistry, 1958
Iron in the Brain
• Non-heme iron in the brain– primary iron deposition not from
bleeding– necessary for dopamine
transmitter function
• Methods to image iron– Field-Dependent Imaging*– Susceptibility Weighted Imaging
(SWI)*– Quantitative Susceptibility Mapping
(QSM)†– R2’ mapping‡
*Pfefferbaum et al. NeuroImage, 2009; *Sullivan et al. Brain Imaging Behav. 2010; †Poynton et al. IEEE Trans Med Imaging,
2015; †Bilgic et al. NeuroImage, 2012; ‡Gelman et al. Radiology 1999; ‡Haacke, et al. MRM 2005
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Non-heme iron susceptibility (T2*) signal losstransverse relaxivity (T2) signal loss
Iron effect greater T2 and T2* weighting greater iron effectless T1 weighting greater iron effect
T2* > T2
DTI sequence has higher spatial resolution and less B0 spatial distortion
Estimating Non-heme Iron Concentration fromStandard NCANDA Protocols
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12-14 years old
Substantia nigra
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15-17 years old
Substantia nigra
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T2_1818-21 years old
Substantia nigra
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Dentate nucleus
Substantia nigraPutamen
Pallidum Red nucleus
R-squared: Signal vs Age
Estimating Age-related Change in Non-heme Iron Concentration from
Standard NCANDA Protocols
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Dentate nucleus
Substantia nigraPutamen
Pallidum Red nucleus
R-squared: Signal vs Age
Estimating Age-related Change in Non-heme Iron Concentration from
Standard NCANDA Protocols
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Dentate nucleus
Substantia nigraPutamen
Pallidum Red nucleus
R-squared: Signal vs Age
Estimating Age-related Change in Non-heme Iron Concentration from
Standard NCANDA Protocols
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Dentate nucleus
Substantia nigraPutamen
Pallidum Red nucleus
R-squared: Signal vs Age
Estimating Age-related Change in Non-heme Iron Concentration from
Standard NCANDA Protocols
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Estimating Non-heme Iron Concentration fromStandard NCANDA Protocols
Dentate nucleus
Substantia nigraPutamen
Pallidum Red nucleus
Dentate nucleus
Red nucleus
Substantia nigra
Putamen
Pallidum
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Estimating Non-heme Iron Concentration fromStandard NCANDA Protocols
SWI index (ppm)
R2
estim
ate
from
DTI
Dentate nucleus
Red nucleus
Substantia nigra
Putamen
Pallidum
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Extending Analysis of Imaging DataSubcortical Brain Iron
Michael De BellisEric Peterson
It is possible to estimate iron deposition using longitudinal and group DTI or fMRI data
Results are more stable with diffusion-weighted DTI than fMRI
Data can be merged across GE and Siemens scanners
DTI iron estimates correlate well with in-vivo QSMsusceptibility measures
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NeuroInformatics
Platform
Extending Analysis of Imaging DataEffects of Initiation of Drinking
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NCANDA 2 Year Follow-upRegional cortical volume trajectories in 483 of 647 no-to-low drinking adolescents meeting imaging and drinking criteria followed longitudinally for 2 years
• 65 transitioned into moderate drinking• 62 transitioned into heavy drinking• 356 remained no-to-low drinker• 1423 MRI brain scans
Cahalan et al. CriteriaAverage drinks per
occasion (last 3months): 1-2 1-2 1-2 3-4 3-4 >4Largest # drinks in year: 1-2 3-4 >4 3-4 >4 >4
<1x/year<1x/month
Frequency 1-3x/month4-8x/month>8x/month
Daily
Moderate DrinkerControl
Heavy Drinker (N=62)
(N=356) (N=65)
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Volu
me
Frontal Cortical Gray Matter
Age
No/low drinkers
Baseline
adapted from Pfefferbaum et al. Cerebral Cortex 2016
MaleFemale
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Volu
me
Frontal Cortical Gray Matter
Age
No/low drinkers
adapted from Pfefferbaum et al. Cerebral Cortex 2016
MaleFemale
Baseline
Corrected for intracranial volume
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Volu
me
Frontal Cortical Gray Matter
Age
No/low drinkers
Baseline
adapted from Pfefferbaum et al. Cerebral Cortex 2016
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
No/low drinkers
Longitudinal1 year
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
Longitudinal2 year
No/low drinkers 356
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Regional Gray Matter Volume SlopesDecline with Age
Male (N=180)Female (N=176)
Frontal Parietal
Temporal Occipital
CingulateInsular
Pfefferbaum et al. in review
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Volu
me
Central White Matter
Age
No/low drinkers
Baseline
adapted from Pfefferbaum et al. Cerebral Cortex 2016
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Volu
me
AgePreliminary unpublished data
No/low drinkers
Longitudinal1 year
Central White Matter
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Volu
me
AgePreliminary unpublished data
Longitudinal2 year
No/low drinkers 356
Central White Matter
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Regional White Matter Volume SlopesDecelerating Growth with Age
Central white matter
Pons
Corpus callosum
Pfefferbaum et al. in review
Male (N=180)Female (N=176)
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
Longitudinal
No/low drinkers 356
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
No/low drinkers 356Transitioners 127
Longitudinal
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
No/low drinkers 356Moderate drinkers 65
Longitudinal
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Volu
me
Frontal Cortical Gray Matter
AgePreliminary unpublished data
No/low drinkers 356Heavy drinkers 62
Longitudinal
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Regions where heavy drinkers have significantly steeper reduction in gray matter volume than no-low drinkers
Adj
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dVo
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dVo
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Age
Age
Adj
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Age
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Moderate
Heavy
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Regional Gray Matter VolumesAccelerated Decline with Initiation of Heavy Drinking
Pfefferbaum et al. in review
No/low
Moderate
Heavy
Frontal Parietal
Temporal Occipital
CingulateInsular
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FreeSurfer Parcellated Cortical Regions34 Regions
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FreeSurfer Parcellated Cortical Regions34 Regions
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FreeSurfer Parcellated Cortical Regions34 Regions
pars opercularis
caudal middle frontal
rostral middle frontal
pars triangularis
superior frontal postcentral
precentral
paracentral
precuneus
cuneus
isthmus cingulate
posterior cingulate
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Pfefferbaum et al. in review
Moderate drinkersHeavy drinkers
Slop
e
Maximum Drinks in Past Year
Superior parietal Inferior parietal
Slop
e
Maximum Drinks in Past Year
Precuneus Total parietal
Slop
e
Slop
e
Maximum Drinks in Past Year Maximum Drinks in Past Year
r=-0.208, p=0.0189Rho=-0.217, p=0.0141
r=-0.236, p=0.0076Rho=-0.239, p=0.0068
r=-0.196, p=0.0271Rho=-0.198, p=0.0256
r=-0.203, p=0.0222Rho=-0.204, p=0.0217
Steeper Regional Parietal TrajectoriesCorrelations with Greater Maximum Drinks in Past Year
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Oregon HSU
SRI
UC San Diego
UPitt
Duke
5 U.S. Recruitment Sites
FUNDINGNIAAA, NIDA, NIMH, NICHD
NeuroInformatics
Platform
SRI+Stanford
Extending Analysis of Imaging DataCortical Myelin
There is a developmental trajectory of cortical myelin increase and decrease
Subcortical Brain IronThere is a developmental trajectory of subcortical non-heme iron deposition
Effects of Initiation of DrinkingInitiation of heavy drinking alters structural cortical developmental trajectory
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