"the potential of multimodal mri for understanding sports concussion" victoria morgan,...
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"THE POTENTIAL OF MULTIMODAL MRI FOR UNDERSTANDING SPORTS CONCUSSION"
Victoria Morgan, Ph.D., Manus Donahue, Ph.D., Megan Strother, M.D., Allen Sills, M.D., Andrew Gregory, M.D., Gary Solomon, Ph.D., and Hakmook Kang, Ph.D.
The Challenge: To identify and quantify brain injury after concussion
• Diagnose acute injury• Monitor recovery• Assess treatment
strategies• Evaluate long term
effects of single and multiple concussions
R
Diffusion Tensor Imaging – Examining White Matter Tracts
• Looks at the direction of diffusion of water along white matter tracts
• Measured by Fractional Anisotrophy (FA)
• Used to assess diffuse axonal injury
Literature:• Many studies reported• Most find decreases related to injury severity or symptoms, but some found increases in some tracts
DTI - Tractography
and Fractional
Anisotrophy
BOLD effect
Blood Oxygen Level Dependence
This is what makes it possible for MRI to detect brain function in addition to anatomy
de-OxyHbOxyHb
(eyes closed) (eyes open)
neurons
- High deOxyHb concentration - Low deOxyHb concentration
Neuronal activity needs oxygen
Blood flow increases bring oxygen
Not all increase in oxygen is used
% OxyHb increases, % deOxyHb decreases
MRI SIGNAL INCREASES !!
This sounds easy!• The signal change is small - <5%
task control
fMRI compares each voxel signal time course to a KNOWN expected time course based on stimulus timing:
Predicted Responses• fMRI is based on the Blood Oxygenation Level Dependent (BOLD) response• It takes about 5 sec for the blood to catch up with the brain• We can model the predicted activation in one of two ways:
1. shift the boxcar by approximately 5 seconds (2 images x 2 seconds/image = 4 sec, close enough)
2. convolve the boxcar with the hemodynamic response to model the shape of the true function as well as the delay
PREDICTED ACTIVATION IN VISUAL AREA
BOXCAR
SHIFTED
CONVOLVEDWITH HRF
PREDICTED ACTIVATION IN OBJECT AREA
Why do we need stats?• We could, in principle, analyze data by voxel surfing: move the cursor
over different areas and see if any of the time courses look interesting
Slice 9, Voxel 1, 0Slice 9, Voxel 0, 0
Even where there’s no brain, there’s noise
Slice 9, Voxel 9, 27Here’s a voxel that responds well whenever there’s visual stimulation
Slice 9, Voxel 13, 41Here’s one that responds well whenever there’s intact objects
Slice 9, Voxel 14, 42
Here’s a couple that sort of show the right pattern but is it “real”?
Slice 9, Voxel 18, 36
Slice 9, Voxel 22, 7
The signal is much higher where there is brain, but there’s still noise
Source: J ody Culham’s fMRI for Dummies web site
Why do we need stats?• We could, in principle, analyze data by voxel surfing: move the cursor
over different areas and see if any of the time courses look interesting
Slice 9, Voxel 1, 0Slice 9, Voxel 0, 0
Even where there’s no brain, there’s noise
Slice 9, Voxel 9, 27Here’s a voxel that responds well whenever there’s visual stimulation
Slice 9, Voxel 13, 41Here’s one that responds well whenever there’s intact objects
Slice 9, Voxel 14, 42
Here’s a couple that sort of show the right pattern but is it “real”?
Slice 9, Voxel 18, 36
Slice 9, Voxel 22, 7
The signal is much higher where there is brain, but there’s still noise
Source: J ody Culham’s fMRI for Dummies web site
Expected time course
Activated voxel time course
Not activated voxel time course
Design of comparison and analyses of differences are the primary challenges of fMRI
REST TASK
Functional MRI – Task Mapping
• Uses BOLD effect• Can look at many taskso languageo memoryo attentiono motor
• Depends on performance
Literature:• Approx 20 studies• Investigations reported
weeks to years after injury• Increases and decreases
in activation levels • Changes with treatments,
severity of symptoms, performance
Language Functional Mapping
Word Generation From Categories
Healthy control
Broca’s and Wernicke’s Area
L
rCVR – cerebrovascular
reactivity
Functional MRI measured with either breath holding or increase CO2 breathing increases vasodilation without increase in metabolic rate of oxygen consumption
No studies found in concussion
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mTBI
Resting Functional Connectivity
• Uses same BOLD signal
• Looks at synchronization
of low frequency
fluctuations in BOLD signal
• Networks are known to
fluctuate in synchrony
• Seed region analysis
Literature:• Approx 8 studies done
• Looked at specific network- default mode• Showing decreases in
network
• One study looked at thalamus – found increased connectivity to cortex
Resting Functional
Connectivity
Connectivity to seed region in precuneus which is part of the default-mode network.
healthy control
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Resting Functional Connectivity to Precuneus
mTBI patient healthy control
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Resting Functional Connectivity to Left Motor Cortex
mTBI patient healthy control
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Long term affects of concussion in retired NFL player
Multimodal MRI protocol
Table 1. MRI Protocol Sequence Measurement Time (min) Localizer 3 Reference parallel imaging calibration 2
T1-weighted anatomy, segmentation 8 T2-weighted anatomy 6
T2-relaxation-under-spin-tagging (TRUST) oxygen extraction fraction (OEF) 5 T1-weighted (matched to fMRI) spatial normalization 6
Resting fMRI functional connectivity (FC) 7 Hypercarbia fMRI regional vascular reactivity (rCVR) 15
Arterial spin labeling (ASL) regional cerebral blood flow (rCBF) 4 T1-weighted (matched to ASL) spatial normalization 3 Diffusion tensor imaging (DTI) structural connectivity (SC) 15
Total scan time: 74 min
Project Ideas
1. To recruit Vanderbilt and Belmont athletes immediately after concussion and scan longitudinally and compare to ImPACT scores during recovery
2. To recruit retired professional athletes to compare MRI measures to neuropsychological exam
Multiple novel measurements at multiple time points
Investigators:
• Victoria Morgan, Ph.D. (VUIIS)• Manus Donahue, Ph.D. (VUIIS) • Gary Solomon, Ph.D. (VSCC) • Megan Strother, M.D. (Radiology) • Andrew Gregory, M.D. (VSCC) • Allen Sills, M.D. (VSCC)• Hakmook Kang, Ph.D. (Biostats)