Functional Neuroimaging: The “Dis”-Connectome
Transcript of Functional Neuroimaging: The “Dis”-Connectome
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Functional Neuroimaging: The “Dis”-Connectome
Salil Soman, MD, MSMike Moseley, PhD
Stanford University S. Seung
Wikipedia
fMRI / DTI - Core of the Connectome
V. Wadeen S. Seung
...Will the Connectome Create New Markets...? The “Connectome” Now on iTunes
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Now! The “Armchair” Connectome The “Connectome” Magnet- PRISMA
The GE-NFL Initiative
NEW YORK, March 11, 2013 -- (NYSE: GE) -- GE and the NFL today announced the Head Health Initiative, a four-year, $60
million collaboration to speed diagnosis and improve treatment for mild traumatic brain injury. The goal of the research and innovation program, guided by healthcare
experts, is to improve the safety of athletes, members of the military and society overall.
The 2013 “BRAIN” Roadmap
http://www.youtube.com/watch?v=EI-VcvwgCgE
“Clarity” Drives “BRAIN” TBI and the “Dis-Connectome”
Role of Advanced MR?
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• Mod to severe detectable with classic MR methods.
• Mild TBI in general has a good prognosis.
• But 15 -30% patients have cognitive, physiological and clinical symptoms at 3 months post injury.
• Majority of patients have negative conventional MR.
• Identify this group at risk for long term disability and early therapy.
WHY ADVANCED MRI?
http://emedicine.medscape.com/article/344973-overview
TBI Background
Wikipedia
Multi-Contrast MR – Key to the Connectome
Structural Imaging
MR Volumetric Analyses
SPM and Freesurfer
VBM Group AnalysesStructural Imaging
Voxel Based Morphometry (VBM) t-test analyses of regional changes over patient populations. Freesurfer/NeuroQuant.
Zhou et al., Mild Traumatic Brain Injury: Longitudinal Regional Brain Volume Changes, Radiology. 2013 J 267(3) 880 90
One year after mild TBI, brain atrophy seenanterior cingulate WM bilaterally left cingulate gyrus isthmus WM, right precuneal GM
VBM Group AnalysisStructural Imaging
Frontal Regions Susceptibile to InjuryTBI Background
http://www.dialogues-cns.com/figures/DialoguesClinNeurosci-13-287-g003.jpg
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http://www.gvsu.edu/cms3/assets/2A1BD006-C757-0356-A2F497F9DC021F20/rsz_astrocyteslstockpd.jpg
TBI Background
http://blog.mcleishorlando.com/blog/wp-content/uploads/2013/03/Axonal_Shear.jpg
“Micro-Structural” MRI for TBI?
Acquisition
Reconstruction
Modeling
Diffusion Tensor Imaging DTI
V. Wedeen
MicroStructural Imaging
Proton Diffusion in GM
10 umOlympus Medical
Proton Diffusion in WM
Olympus Medical 10 um
ADC ADC xx ADC xy ADC xz
ADC xy ADC yy ADC yz
ADCxz ADC yz ADC zz
Tensor
Y
XZ
Magnet axis Fiber axis
Diffusion Tensor Imaging
MicroStructural Imaging
Magnet axis
ADC FA x
y
z
DTI
“FA”
map
Diffusion
Model
Diffusion
Pathways
Fiber
Tractography
Color
“FA”
map
One Way to Display DTI: TractographyOne Way to Display DTI: TractographyMicroStructural Imaging
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DWI inStroke
DWI vs. DTI: Which is Which?DWI vs. DTI: Which is Which?
DWI“ADC”DWI“ADC”
DTI“FA”
DWI inScreening
CNS
Non-NeuroDWI
DWI inMSK
FA in CNSdisease
Fiber tracking
DTI FA
DTI in cognition
Technique Development
Hulkower MB, Poliak DB, Rosenbaum SB, et al. A Decade of DTI in Traumatic Brain Injury: 10 Years and 100 Articles Later. AJNR. American journal of neuroradiology. Jan 10 2013.
• The most commonly identified regions of abnormal FA or MD in DTI studies of TBI:• Corpus callosum, • Frontal lobe, • Internal capsule, • Cingulum
DTI and TBI
DTI Multi-Subject Statistical AppsDTI Modeling and Statistics
http://fsl.fmrib.ox.ac.uk/fslcourse/lectures/fdt.pdf
Tract-Based Spatial Stats (TBSS)FSL (FMRIB)
DTI Modeling and Statistics
S.M. Smith, M. Jenkinson, H. Johansen-Berg, D. Rueckert, T.E. Nichols, C.E. Mackay, K.E. Watkins, O. Ciccarelli, M.Z. Cader, P.M. Matthews, and T.E.J. Behrens. Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. NeuroImage,
31:1487-1505, 2006.
Automated White Matter Tract Segmentation (TRACULA)
Freesurfer
TRActs Constrained by UnderLying Anatomy
DTI Modeling and Statistics
FreeSurfer Module FreeSurfer.net
T1 T2 iso trace FA Colormap FLAIR
SWI
Adult atlas MRIStudio.org
DTI Modeling and Statistics
T1 T2 iso trace FA Colormap
Pediatric atlas (24M)
T1 T2 iso trace FA Colormap
Neonatal atlas
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• The number of b values can provide additional data for modeling the microstructure of the brain.
• Conventional DTI sequences tend to use the single b value of 1000, plus some number of b0 images.
• Having additional b value images other than b0 enables a number of different modeling techniques.
• Conventional DTI is not enough!
“Higher Order” DTIWhy Make This Harder?
Higher Order DTI DTI is NOT Simple : Need Higher Order Tensors
Diffusion Kurtosis Imaging DKI• Assumes substantially non-gaussian distribution of water
diffusion
• May better evaluate diffusion properties outside of highly organized large white matter tracts.
Zhuo J, Xu S, Proctor JL, et al. Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury. NeuroImage. Jan 2 2012;59(1):467-477.
Higher Order DTI
• within 1 year after mTBI exhibited altered DTI-and DKI measures in thalamus and internal capsule (c/w controls)
• > 1 year after mTBI had differences in splenium of the corpus callosum and the centrum semiovale.
• Cognitive impairment was correlated with Mean Kurtosis (MK) in the thalamus and the internal capsule.
Zhuo J, Xu S, Proctor JL, et al. Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury. NeuroImage. Jan 2 2012;59(1):467-477.
DKI in TBI
DTI in TBI
Diffusion Full-Space Imaging – 150 Directions –12 minutes minimum
DSI, QSI, RSI – The Ultimate DTI?
Higher Order DTI
http://dsi-studio.labsolver.org
Neurite Orientation Dispersion and Density Imaging
Neurite Modeling (NODDI)Higher Order DTI
UCL Package
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Quantitative Susceptibility MappingWhat and Why?
Microstructural Imaging - QSM
•DTI is a sensitive measure of WM directions / connectivity but needs more work for measuring integrity. •QSM is faster with higher resolution and 3D for WM mapping.•QSM natural extension of GRE and is both bleed/WM sensitive.
• Higher• More paramagnetic
microstructures
• Lower• More diamagnetic
microstructures
Physical Properties of QSM
Microstructural Imaging - QSM
“The total susceptibility of a cerebral microbleed measuredby using QSM is a physical property that is independent
of echo time.”
Liu T, Surapaneni K, Lou M, et al. Cerebral microbleeds: burden assessment by using quantitative susceptibility mapping. Radiology. Jan 2012;262(1):269-278.
QSM Shows Bleeds Independent of TE
Microstructural Imaging - QSM
Negative Correlation between TBI patient only left (not right) lateral orbitofrontal cortex susceptibility and performance on Verbal Test, controlling for age
Soman et al. Preliminary results 2013.
QSM in TBI
Microstructural Imaging - QSM
A B C
D E F
QSM is Ideal for VBM
Microstructural Imaging - QSM
fMRI is BOLDfMRI is BOLD
FeFe
NN
NN
O = OO = O
oxyhemoglobinoxyhemoglobin
FeFe
NN
NN
deoxyhemoglobindeoxyhemoglobin
HbO2HbO2 HbHb
Hb4 unpaired electrons
paramagneticHigh ² �
Hb4 unpaired electrons
paramagneticHigh ² �
HbO2diamagnetic
Low ² �
HbO2diamagnetic
Low ² �
Functional MRI - fMRI
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The Brain Does Not Sleep - Resting State fMRIThe Brain Does Not Sleep - Resting State fMRIFunctional MRI - fMRI
Resting State RS-fMRI The Other Connectivity
Functional Imaging
Zhou Y, et al. Default-mode network disruption in mild traumatic brain injury. Radiology. Dec 2012;265(3):882-892.
When compared with DMN patterns in the control group (A), the patient group (B) showed significantly decreased connectivity in the posterior portion (arrowheads) and increased connectivity in the anterior portion (arrows) of the DMN.
RS-fMRI in TBIFunctional Imaging
RS-fMRI BOLD FluctuationsRelated to CBV
RS-fMRI BOLD FluctuationsRelated to CBV
Related To NetworkDelays (!)
Multispectral Data Fusion
The Dis-Connectome
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Structural Connectivity Mapping
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Diffusion Tensor Imaing Volumetrics Connectivity Matrix
• Diffusion Tensor and volumetric images combined to generate connectivity matrices.
• Matrices then converted to graphs representing brain connectivity.
The Connectome – Putting It All Together
Structural Connectivity MappingThe Connectome – Putting It All Together
Structural Connectivity MappingThe Connectome – Putting It All Together
• Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency.
• A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex.
• Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics.
Pandit AS, Expert P, Lambiotte R, et al. Traumatic brain injury impairs small-world topology. Neurology. May 14 2013;80(20):1826-1833.
Controls
TBI
The “Small World Network” - TBIThe Connectome – Putting It All Together
Many Thanks: Keith MainFranco PestilliGautam PrasadNils FolkertNatalie HanAnna Clare MillazzoNanjie GongDeqiang QiuMurat AksoyElizabeth HitchnerJyoti BhatZungho (Wesley) ZunShannon BuckleyBernard NgJonas RichiardiDawn LaGuo Jia GuoFariah Mahzabeen
Solil SomanGreg ZaharchukAllyson RosenBrian WandellWei ZhouAndy QuonMichael GreciusJerry YesavageGeoff KerchnerEric WongChunlei LiuJames HarrisJames BrewerKaren HirschBooil Jo
R21 NS081416
J. Wesson AshfordAnsgar FurstMaheen M. AdamsonRobert DoughertyLaura LazaroniLeah FriedmanJae Mo ParkSamantha HoldsworthLinda IsaacLisa Kinoshita
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Thank you
“Metabolic” PET-MR (mMR)“Metabolic” PET-MR (mMR)
Siemens mMR “Biograph”
Siemens mMR “Biograph”
• The sample consisted of 57 veterans (7 females), mean age of 46.8 yrs. (median: 45.1), 31 mild TBI, 5 moderate TBI and 43 with PTSD.
• Glucose metabolism decreased significantly with increasing TBI severity in the right precuneus and left angular gyrus.
• VOI analyses with FWE multiple comparison correction at p < .05 confirmed the robustness of the effect.
Soman et al. Preliminary results 2013.
PET-MR and TBI
Beyond the Connectome – Room for PET?
SI=ke(-� � G [- �/3] ADC) =ke(-b ADC)
where b=0-1000 sec/mm2
SI=ke(-� � G [- �/3] ADC) =ke(-b ADC)
where b=0-1000 sec/mm2
Proton Diffusion can be Measured as the “ADC”
Proton DiffusionProton Diffusion
0 090 RF 180 RF
0 0
GG GG
b0b0
ADC map
= 40 msec���� msec
b1000b1000 ADCADC
22 22 22
MicroStructural Imaging
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Thalamic Nuclei Evaluation
Krauth et al. A mean three-dimensional atlas of the human thalamus: generation from multiple histological data. Neuroimage. 2010 Feb 1;49(3):2053-62; Squarcina et al. A robust method for investigating thalamic white matter tracts after traumatic brain injury. NeuroImage. Nov 1 2012;63(2):779-788.
• Damage to the structural connections of the thalamus is a frequent feature of traumatic brain injury (TBI) and could be a key factor in clinical outcome
• Multiple thalamic nuclei atlases available.
DTI in TBI