Cortical diffusion imaging Alard Roebroeck Maastricht Brain Imaging Center (MBIC) Dept. of Cognitive Neuroscience Faculty of Psychology & Neuroscience Maastricht University Diffusion MRI In vivo & Ex vivo Overview Models & tractography Diffusion MRI & Histology Diffusion MRI Validation Human brain connectivity Conclusions 1
Diffusion MRI WM Anisotropic diffusion: hindered or restricted D > D GM Le Bihan, 2003 Probe with diffusion gradient directions Diffusion MRI Higher B0 field T2 decay Lower B0 field Excitation Refocussing RF Gradient Signal FID diffusion gradient TE/2 diffusion gradient Un-weighted signal (S 0 ) Diffusion-weighted signal (S) TE Attenuation acquisition 2
Hardware: Magnets, gradients, RF 3T dwmri, 40mT/m, 8Ch receive 2.5mm voxels, relative resolution 1x 3T dwmri, 40mT/m, 32Ch receive 1.8mm voxels, relative resolution 2.7x 7T dwmri, 70mT/m, 32Ch receive 1.0mm voxels, relative resolution 15.6x 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 resolution D 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 3
Signal models & tractography Single direction vs. Multiple directions Local vs. Global Deterministic vs. Probabilistic Diffusion Tensor Imaging (DTI) Vs. Ball&Sticks (BEDPOSTX) Spherical Deconvolution (CSD) Diffusion Spectrum Imaging (DSI) Streamline tractography Vs. PiCO BEDPOSTX Gibbs tractography Diffusion MRI In vivo & Ex vivo Overview Models & tractography Diffusion MRI & Histology Diffusion MRI Validation Human brain connectivity Conclusions 4
DTI direction validation a: Gray matter b: Crossing directions in white matter c: Single direction in white matter Seehaus et al., submitted Tractography validation Carbocyanine dyes Selectively stain single axons along length 2D Histology slices 70um slices every 350um 3D dmri 391x391x1000µm Seehaus et al., Cerebral Cortex, 2012 5
Tractography validation Human optic chiasm 9.4T 300 mt/m 156um 2 x 312um b = 1500s/mm 2 Roebroeck et al., NI, 2008 Diffusion MRI In vivo & Ex vivo Overview Models & tractography Diffusion MRI & Histology Diffusion MRI Validation Human brain connectivity Conclusions 6
Human multiscale connectivity Macroscale Mesoscale Microscale Nanoscale In-vivo dmri Ex-vivo LM Ex-vivo dmri Ex-vivo EM µm 3 : whole human brain 10 15 Long-range Short-range Topographic Layered projection Intracortical organization circuits Layer of avg. large projection termination Axonal density & diameters Synaptic contacts 10 12 10 9 10 6 10 0 10-3 10-6 10 4 Neurotransmitters Receptors µm: 10 5 10 2 10 1 10 0 10-1 10-2 10-3 cm mm µm nm 10-9 Macroscale connectivity: whole brain Post mortem 0.73mm b=4500s/mm 2 3T 40 mt/m In vivo 2.00mm b=1000s/mm 2 Miller et al., NeuroImage, 2011 7
Macroscale connectivity: whole brain 3T 40 mt/m 9.4T ex vivo, 330um Miller et al., NeuroImage, 2011 Macroscale connectivity: whole brain 7T / 70mT/m in vivo, 800um Heidemann et al., NeuroImage, 2012 3T / 80mT/m in vivo, 1mm 8
Human multiscale connectivity Macroscale Mesoscale Microscale Nanoscale In-vivo dmri Ex-vivo LM Ex-vivo dmri Ex-vivo EM µm 3 : whole human brain 10 15 Long-range Short-range Topographic Layered projection Intracortical organization circuits Layer of avg. large projection termination Axonal density & diameters Synaptic contacts 10 12 10 9 10 6 10 0 10-3 10-6 10 4 Neurotransmitters Receptors µm: 10 5 10 2 10 1 10 0 10-1 10-2 10-3 cm mm µm nm 10-9 Mesoscale connectivity: cerebellum Dell Aqua, Cerebellum, 2013 Micro-tractography 9
Mesoscale connectivity: cerebellum Diffusion Histology Dell Aqua, Cerebellum, 2013 Human multiscale connectivity Macroscale Mesoscale Microscale Nanoscale In-vivo dmri Ex-vivo LM Ex-vivo dmri Ex-vivo EM µm 3 : whole human brain 10 15 Long-range Short-range Topographic Layered projection Intracortical organization circuits Layer of avg. large projection termination Axonal density & diameters Synaptic contacts 10 12 10 9 10 6 10 0 10-3 10-6 10 4 Neurotransmitters Receptors µm: 10 5 10 2 10 1 10 0 10-1 10-2 10-3 cm mm µm nm 10-9 10
Intracortical connectivity 9.4T diffusion MRI, Average of 12 diffusion-weighted images, 160um in-plane Intracortical connectivity 9.4T ex vivo, 330um isotropic resolution, 60 directions DTI, major eigenvector directions 11
29-5-2015 Intracortical connectivity Sengupta et al., ISMRM, 2015 9.4T ex vivo cat, 250um isotropic resolution, 48 directions DTI, major eigenvector directions Intracortical connectivity Leuze, Cerb. Cort., 2012 12
Intracortical connectivity Aggarwall, NI, 2014 Diffusion MRI In vivo & Ex vivo Overview Models & tractography Diffusion MRI & Histology Diffusion MRI Validation Human brain connectivity Conclusions 13
Diffusion MRI Challenging ex vivo Conclusions But delivers high resolution Crucial for anatomy Takes dmri into the cortex Human multiscale connectivity Macroscale Mesoscale Microscale Nanoscale In-vivo dmri Ex-vivo LM Ex-vivo dmri Ex-vivo EM µm 3 : whole human brain 10 15 Long-range Short-range Topographic Layered projection Intracortical organization circuits Layer of avg. large projection termination Axonal density & diameters Synaptic contacts 10 12 10 9 10 6 10 0 10-3 10-6 10 4 Neurotransmitters Receptors µm: 10 5 10 2 10 1 10 0 10-1 10-2 10-3 cm mm µm nm 10-9 Extensively cover the mesoscale Extend Hi-res field of view 14
Whole ex-vivo brain MRI 9.4 Tesla 7 Tesla 2 mm 1 mm 0.33 mm Ultra-high field MRI 9.4T whole human brain 330µm isotropic Specialized RF coils Human multiscale connectivity Macroscale Mesoscale Microscale Nanoscale In-vivo dmri Ex-vivo LM Ex-vivo dmri Ex-vivo EM µm 3 : whole human brain 10 15 Long-range Short-range Topographic Layered projection Intracortical organization circuits Layer of avg. large projection termination Axonal density & diameters Synaptic contacts 10 12 10 9 10 6 10 0 10-3 10-6 10 4 Neurotransmitters Receptors µm: 10 5 10 2 10 1 10 0 10-1 10-2 10-3 cm mm µm nm 10-9 Multi-modal imaging Large 3D FoV light microscopy on the same tissue 15
Juelich Anca Oros-Puesquens Daniel Brenner Jon Shah Darmstadt Ralf Galuske Hans-Juergen Bratzke Minneapolis Gregor Adriany Thanks Maastricht Matteo Bastiani Arne Seehaus Arko Sengupta Valentin Kemper Desmond Tse Benedikt Poser Rainer Goebel Grants European Research Council ERC-StG MULTICONNECT #639938 16