"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

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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

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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)