The Potential of Multimodal MRI for Understanding Sports Concussion

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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
R
• Diagnose acute injury
• Monitor recovery
• Assess treatment
strategies
• Evaluate long term
effects of single and
multiple concussions
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
(eyes open)
(eyes closed)
neurons
OxyHb
de-OxyHb
- 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
R
D
PREDICTED ACTIVATION IN VISUAL AREA
PREDICTED ACTIVATION IN OBJECT AREA
fMRI compares each voxel signal time course
Slicebased
9, Voxel
to a KNOWN expected time course
on0, 0
Even where there’s no brain, there’s noise
stimulus timing:
REST TASK
Why do we need stats?
principle, analyze data by voxel surfing: move the cu
Slice
9, Voxel 9,
27 intere
t areas and see if any of the time
courses
look
Activated
voxel time course
VED
RF
0, 0
Expected time course
Design of comparison and
analyses of differences are
the primary challenges of
fMRI
there’s noise
Slice 9, Voxel 1, 0
Here’s a voxel that responds well whenever
there’s visual stimulation
The
high
is br
still
Slice 9,voxel
Voxel
22,
7
Not activated
time
course
Slice 9, Voxel 13, 41
Here’s one that responds well whenever
Functional MRI – Task Mapping
• Uses BOLD effect
• Can look at many tasks
o language
o memory
o attention
o 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
R
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
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
R
Connectivity to
seed region in
precuneus
which is part of
the defaultmode network.
healthy control
Resting Functional Connectivity to Precuneus
R
mTBI patient
healthy control
Resting Functional Connectivity to Left Motor Cortex
R
mTBI patient
healthy control
Long term affects of concussion in retired NFL player
Multimodal MRI protocol
Table 1. MRI Protocol
Sequence
Localizer
Reference
T1-weighted
T2-weighted
T2-relaxation-under-spin-tagging (TRUST)
T1-weighted (matched to fMRI)
Resting fMRI
Hypercarbia fMRI
Arterial spin labeling (ASL)
T1-weighted (matched to ASL)
Diffusion tensor imaging (DTI)
Measurement
Time (min)
3
parallel imaging calibration
2
anatomy, segmentation
8
anatomy
6
oxygen extraction fraction (OEF)
5
spatial normalization
6
functional connectivity (FC)
7
regional vascular reactivity (rCVR)
15
regional cerebral blood flow (rCBF)
4
spatial normalization
3
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)
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