(D-151) Changes in Cerebral Blood Flow Associated with Head Impact Exposure in Youth Football Players

Saturday, October 14, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row D - Poster # 151

Presenting Author(s)

PR

Pranjal Rai

Computer Science Student
The University of Texas at Austin
Dallas, Texas, United States

Primary Investigator(s)

ML

Megan Lipford

Assistant Professor, Radiology
Wake Forest University, United States

Co-Author(s)

RB

Richard Barcus

Programmer/Analyst III
Wake Forest University, United States
JK

Jeongchul Kim

Assistant Professor, Radiology
Wake Forest University, United States
MK

Mohammad Kawas

Clinical Researcher
Wake Forest University, United States
JU

Jillian Urban

Assistant Professor
Wake Forest University School of Medicine, United States
ED

Elizabeth M. Davenport, Ph.D.

ASSISTANT PROFESSOR
University of Texas Southwestern Medical Center, United States
DR

Daryl Rosenbaum

Professor
UT Southwestern Medical Center, United States
AP

Alexander Powers

Neurosurgeon
Total Spine & Brain Institute, United States
JS

Joel Stitzel

Professor, Biomedical Engineering
Wake Forest University School of Medicine, United States
JM

Joseph A. Maldjian, M.D.

PROFESSOR & DIVISION CHIEF
University of Texas Southwestern Medical Center, United States

Last Author(s)

CW

Christopher Whitlow

Faculty
WFU, United States

Introduction:: American football is the most popular sport in the United States with over 5 million participants, of which approximately 3 million are youth players between the ages of 8 to 12 years [1]. However, tackle football has the highest incidence of sports-related concussion (SRC), which is considered a mild Traumatic Brain Injury (mTBI) [1]. mTBI accounts for approximately 90% of all TBIs and is one of the leading causes of pediatric death and disability in the world [2]. In children, chronic mTBI can have prolonged effects on the brain and can take time to reach complete recovery. Cerebral blood flow (CBF) measured by Magnetic Resonance Imaging (MRI), quantifies the amount of perfusion to the brain (measured in units of mL of blood/100 g of tissue/minute). Increased levels of CBF are linked to poor recovery after pediatric concussion, specifically in temporal and frontal regions [2, 3]. Conversely, decreased levels of CBF are linked to neuroinflammation post-mTBI [4]. While many head-related injuries in football are concussions, most of the head impacts are sub-concussive, meaning they do not cause any concussion symptoms but may result in long-term effects. Research about repetitive head impact is primarily centered around collegiate and professional players. The purpose of this study is to examine how CBF changes in the brain due to repetitive, sub-concussive head impact exposure experienced across a season of youth football. We hypothesized that head impact exposure (HIE) will be associated with CBF changes in the brain.

Materials and Methods:: Using the Head Impact Telemetry System (HITS^TM), HIE in 54 football players between the ages of 10 and 14 years was assessed across a single season using the combined probability risk-weighted cumulative exposure (RWE_cp) metric [5]. None of the subjects obtained or had a history of concussion. Pulsed-continuous Arterial Spin Labeling (pcASL), a type of MRI, was done before and after the season to measure CBF changes in the brain across a season of youth football. The pcASL data was then motion-corrected and used to create CBF maps that were smoothed and normalized to 1.5 mm isotropic. A gray matter mask was applied to each subject’s delta CBF map. An ordinary least squares (OLS) linear regression was performed on each voxel between Δ CBF and RWE_cp, correcting for age and days between the pre and postseason scans. From this regression, a p-value map was constructed, and then binarized (α = 0.05) to identify voxels that significantly correlated with RWE_cp. A clustering analysis was then conducted to create a cluster map, where significant voxels were grouped together. A cluster threshold of 254 voxels was determined by AFNI’s 3dClustSim using the gray matter mask, and FWHM of 3.4mm x 3.4mm x 6mm as the smoothing kernel (the original resolution of ASL acquisition) as inputs. Using the Automatic Anatomical Labeling (AAL) atlas [6], the locations of the clusters in relation to the regions of interest (ROIs) in the brain were determined.

Results, Conclusions, and Discussions::

There were 6 clusters that surpassed the cluster threshold. Most of the clusters showed a positive and direct relationship between the ΔCBF and RWE_cp, as seen from the positive mean t-statistics in Table 1, and the orange/yellow clusters in Figure 1. However, cluster 1 (the largest cluster) and cluster 4 had an inverse relationship between RWE_cp and ΔCBF, seen from the negative mean t-statistic in Table 1 and the blue clusters in Figure 1. 1415 voxels show a positive relationship compared to the 982 voxels that show a negative relationship between HIE and ΔCBF.

The positive relationship between CBF and HIE in the majority of the significant clusters and voxels indicates that repetitive HIE may be linked to increased perfusion, which is also visible during poor recovery post-mTBI [3] and could indicate the healing process of damaged brain tissue. Conversely, the areas with a negative relationship with HIE could indicate longer-term brain deficits due to HIE [7]. Previous studies have shown increases in CBF can be associated with poor post-concussion recovery, while decreases in CBF can be associated with neuroinflammation. after concussion. Further analysis of the effects of sub-concussive HIE with CBF is required. This study contributes to the literature related to post-concussive investigations in youth. Future studies should compare CBF changes in relation to HIE in other sports, specifically contact sports with female and male players, followed over a longer time frame with multiple longitudinal time points.

Acknowledgements (Optional): : This project was supported in part by the NSF REU Site (Award #1950281) in the Department of Biomedical Engineering at Wake Forest University of School of Medicine, NIH/NINDS iTAKL: Imaging Telemetry And Kinematic modeLing in youth football-High School (R01NS094410), and NIH/NINDS iTAKL: Imaging Telemetry And Kinematic modeLing in youth football (R01NS082453).

References (Optional): :

[1] Kontos AP, Elbin RJ, Fazio-Sumrock VC, et al. Incidence of sports-related concussion among youth football players aged 8-12 years. J Pediatr 2013;163(3):717-720

[2] Barlow KM, Iyer K, Yan T, Scurfield A, Carlson H, Wang Y. Cerebral Blood Flow Predicts Recovery in Children with Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury. J Neurotrauma. 2021 Aug 15; 38(16):2275-2283.

[3] Barlow KM, Marcil LD, Dewey D, Carlson HL, MacMaster FP, Brooks BL, Lebel RM. Cerebral Perfusion Changes in Post-Concussion Syndrome: A Prospective Controlled Cohort Study. J Neurotrauma. 2017 Mar 1;34(5):996-1004.

[4] Sankar SB, Pybus AF, Liew A, Sanders B, Shah KJ, Wood LB, Buckley EM. Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury. Neurobiol Dis. 2019 Apr;124:544-554.

[5] Cobb, B.D., Urban, J.E., Davenport, E.M. et al. Head Impact Exposure in Youth Football: Elementary School Ages 9-12 Years and the Effect of Practice Structure. Ann Biomed Eng 41, 2463-2473 (2013). https://doi.org/10.1007/s10439-013-0867-6

[6] Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002 Jan;15(1):273-89.

[7] Wood, H. Cerebral blood flow is linked to sports-related concussion outcomes. Nat Rev Neurol 11, 185 (2015). https://doi.org/10.1038/nrneurol.2015.40