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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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Page 1: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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

Page 2: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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

Page 5: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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

Page 7: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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

Page 9: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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

Page 10: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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

Page 14: Cortical diffusion imaging - Organization for Human … Materials/Anatomy_Roebroeck...Cortical diffusion imaging ... • Diffusion MRI & Histology ... Seehaus et al., Cerebral Cortex,

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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