"The Potential of Multimodal MRI for Understanding Sports Concussion"

1. "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.

2. 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

3. 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

4. DTI - Tractography and Fractional Anisotrophy

5. BOLD effect Blood Oxygen Level Dependence This is what makes it possible for MRI to detect brain function in addition to anatomy

6. (eyes open) (eyes closed) neurons OxyHb de-OxyHb - Low deOxyHb concentration - High 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 !!

7. task control This sounds easy! • The signal change is small - <5%

8. fMRI compares each voxel signal time course to a KNOWN expected time course based on stimulus timing: REST TASK Activated voxel time course Expected time course Design of comparison and analyses of differences are the primary challenges of fMRI Not activated voxel time course

9. Functional MRI – Task Mapping • Uses BOLD effect • Can look at many tasks • language • memory • attention • 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

10. L Language Functional Mapping Word Generation From Categories Healthy control Broca’s and Wernicke’s Area

11. R 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 mTBI

12. 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

13. R Resting Functional Connectivity Connectivity to seed region in precuneus which is part of the default-mode network. healthy control

14. Resting Functional Connectivity to Precuneus R mTBI patient healthy control

15. Resting Functional Connectivity to Left Motor Cortex R mTBI patient healthy control

16. Long term affects of concussion in retired NFL player

17. Multimodal MRI protocol

18. Project Ideas • To recruit Vanderbilt and Belmont athletes immediately after concussion and scan longitudinally and compare to ImPACT scores during recovery • To recruit retired professional athletes to compare MRI measures to neuropsychological exam Multiple novel measurements at multiple time points

19. 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)