29-5-2015
1
Cortical diffusion imaging
Alard Roebroeck
Maastricht Brain Imaging Center (MBIC)
Dept. of Cognitive Neuroscience
Faculty of Psychology & Neuroscience
Maastricht University
Overview
• Diffusion MRI– In vivo & Ex vivo
– Models & tractography
• Diffusion MRI & Histology– Diffusion MRI Validation
– Human brain connectivity
• Conclusions
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Diffusion MRI
Le Bihan, 2003
D|| > D┴
WM
GM
Anisotropic diffusion:hindered or restricted
Probe with diffusiongradient directions
Diffusion MRI
RF
Gradient
TE/2
Excitation
Signal
FIDAttenuation
Un-weighted signal (S0)
Diffusion-weighted signal (S)
TE
acquisition
Refocussing
T2 decayHigher B0 field
Lower B0 field
diffusiongradient
diffusiongradient
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3T dwMRI, 40mT/m, 8Ch receive2.5mm voxels, relative resolution 1x
3T dwMRI, 40mT/m, 32Ch receive1.8mm voxels, relative resolution 2.7x
7T dwMRI, 70mT/m, 32Ch receive1.0mm voxels, relative resolution 15.6x
Hardware: Magnets, gradients, RF
In vivo dMRI data
Post mortem tissue
• Compared to in-vivo:– Reduced Diffusion coefficients
– Reduced T2 and T2*
– Reduced T1
– Different MRI acquisitions:• Highly segmented (multi-shot)
• 3D (instead of 2D)
• Very long acquisitions
– Much higher resolutionD’Arceuil et al, NI 2007a,b; Dyrby et al., NI 2007; Roebroeck et al., NI 2008, McNab et al., NI 2009; Dyrby et al., HBM, 2011; Miller et al., NI 2011, 2012
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Signal models & tractographySingle direction vs. Multiple directions
Deterministic vs. Probabilistic
Local vs. Global
• Diffusion Tensor Imaging (DTI)Vs.
• Ball&Sticks (BEDPOSTX)• Spherical Deconvolution (CSD)• Diffusion Spectrum Imaging (DSI)• I
• Streamline tractographyVs.
• PiCO• BEDPOSTX• Gibbs tractography• I
Overview
• Diffusion MRI– In vivo & Ex vivo
– Models & tractography
• Diffusion MRI & Histology– Diffusion MRI Validation
– Human brain connectivity
• Conclusions
29-5-2015
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DTI direction validation
a: Gray matterb: Crossing directions in white matterc: Single direction in white matter
Seehaus et al., submitted
– Carbocyanine dyes• Selectively stain single
axons along length
– 2D Histology slices • 70um slices every
350um
– 3D dMRI• 391x391x1000µm
Seehaus et al., Cerebral Cortex, 2012
Tractography validation
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Tractography validation
Roebroeck et al., NI, 2008
• Human optic chiasm
• 9.4T
• 300 mT/m
• 156um2 x 312um
• b = 1500s/mm2
Overview
• Diffusion MRI– In vivo & Ex vivo
– Models & tractography
• Diffusion MRI & Histology– Diffusion MRI Validation
– Human brain connectivity
• Conclusions
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Human multiscale connectivity
Long-range association projections
µm: 10-210-1100101102103104
10-610-31001031061091012
cm mm µm nm 10-3
10-9µm3:
105
1015
Short-range association projections
LayeredIntra-cortical circuits
wholehumanbrain
In-vivo dMRI
Ex-vivo dMRI
Ex-vivo LM
Ex-vivo EM
Macroscale Mesoscale Microscale Nanoscale
Synapticcontacts
Neuro-transmittersReceptors
Layer ofavg. largeprojectiontermination
Axonaldensity &diameters
Topographicprojectionorganization
Macroscale connectivity: whole brain
• 3T
• 40 mT/m
Miller et al., NeuroImage, 2011
Post mortem0.73mmb=4500s/mm2
In vivo2.00mmb=1000s/mm2
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Macroscale connectivity: whole brain
• 3T
• 40 mT/m
Miller et al., NeuroImage, 2011
9.4T ex vivo, 330um
7T / 70mT/m in vivo, 800umHeidemann et al., NeuroImage, 2012
Macroscale connectivity: whole brain
3T / 80mT/m in vivo, 1mm
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Human multiscale connectivity
Long-range association projections
µm: 10-210-1100101102103104
10-610-31001031061091012
cm mm µm nm 10-3
10-9µm3:
105
1015
Short-range association projections
LayeredIntra-cortical circuits
wholehumanbrain
In-vivo dMRI
Ex-vivo dMRI
Ex-vivo LM
Ex-vivo EM
Macroscale Mesoscale Microscale Nanoscale
Synapticcontacts
Neuro-transmittersReceptors
Layer ofavg. largeprojectiontermination
Axonaldensity &diameters
Topographicprojectionorganization
Dell’Aqua, Cerebellum, 2013
Micro-tractography
Mesoscale connectivity: cerebellum
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Mesoscale connectivity: cerebellum
Dell’Aqua, Cerebellum, 2013
Diffusion Histology
Human multiscale connectivity
Long-range association projections
µm: 10-210-1100101102103104
10-610-31001031061091012
cm mm µm nm 10-3
10-9µm3:
105
1015
Short-range association projections
LayeredIntra-cortical circuits
wholehumanbrain
In-vivo dMRI
Ex-vivo dMRI
Ex-vivo LM
Ex-vivo EM
Macroscale Mesoscale Microscale Nanoscale
Synapticcontacts
Neuro-transmittersReceptors
Layer ofavg. largeprojectiontermination
Axonaldensity &diameters
Topographicprojectionorganization
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Intracortical connectivity
9.4T diffusion MRI, Average of 12 diffusion-weighted images, 160um in-plane
9.4T ex vivo, 330um isotropic resolution, 60 directionsDTI, major eigenvector directions
Intracortical connectivity
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9.4T ex vivo cat, 250um isotropic resolution, 48 directionsDTI, major eigenvector directions
Intracortical connectivity
Sengupta et al., ISMRM, 2015
Leuze, Cerb. Cort., 2012
Intracortical connectivity
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Intracortical connectivity
Aggarwall, NI, 2014
Overview
• Diffusion MRI– In vivo & Ex vivo
– Models & tractography
• Diffusion MRI & Histology– Diffusion MRI Validation
– Human brain connectivity
• Conclusions
29-5-2015
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Conclusions
• Diffusion MRI– Challenging ex vivo
– But delivers high resolution
– Crucial for anatomy
– Takes dMRI into the cortex
Human multiscale connectivity
Long-range association projections
µm: 10-210-1100101102103104
10-610-31001031061091012
cm mm µm nm 10-3
10-9µm3:
105
1015
Short-range association projections
LayeredIntra-cortical circuits
wholehumanbrain
In-vivo dMRI
Ex-vivo dMRI
Ex-vivo LM
Ex-vivo EM
Macroscale Mesoscale Microscale Nanoscale
Synapticcontacts
Neuro-transmittersReceptors
Layer ofavg. largeprojectiontermination
Axonaldensity &diameters
Topographicprojectionorganization
• Extensively cover the mesoscale– Extend Hi-res field of view
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Whole ex-vivo brain MRI
2 mm
1 mm
Specialized RF coils
7 Tesla9.4 Tesla
Ultra-high field MRI
9.4T whole human brain 330µm isotropic
0.33 mm
Human multiscale connectivity
Long-range association projections
µm: 10-210-1100101102103104
10-610-31001031061091012
cm mm µm nm 10-3
10-9µm3:
105
1015
Short-range association projections
LayeredIntra-cortical circuits
wholehumanbrain
In-vivo dMRI
Ex-vivo dMRI
Ex-vivo LM
Ex-vivo EM
Macroscale Mesoscale Microscale Nanoscale
Synapticcontacts
Neuro-transmittersReceptors
Layer ofavg. largeprojectiontermination
Axonaldensity &diameters
Topographicprojectionorganization
• Multi-modal imaging– Large 3D FoV light microscopy on the same tissue
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ThanksMaastrichtMatteo BastianiArne SeehausArko SenguptaValentin KemperDesmond TseBenedikt PoserRainer Goebel
DarmstadtRalf GaluskeHans-Juergen Bratzke
JuelichAnca Oros-PuesquensDaniel BrennerJon Shah
MinneapolisGregor Adriany
GrantsEuropean Research CouncilERC-StG MULTICONNECT #639938