TY - JOUR
T1 - Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players
T2 - A Pilot Study
AU - Kawata, Keisuke
AU - Steinfeldt, Jesse A.
AU - Huibregtse, Megan E.
AU - Nowak, Madeleine K.
AU - Macy, Jonathan T.
AU - Kercher, Kyle
AU - Rettke, Devin J.
AU - Shin, Andrea
AU - Chen, Zhongxue
AU - Ejima, Keisuke
AU - Newman, Sharlene D.
AU - Cheng, Hu
N1 - This manuscript has been released as a pre-print at bioRxiv [Kawata et al. (71)]. This work was partly supported by the Research Funds from the Indiana University Office of Vice President for Research (to KKa), Indiana University Women’s Philanthropy Council (to KKa), and Indiana CTSI pilot core fund (to KKa and SN). Sponsors had no role in the design or execution of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
PY - 2020/11/16
Y1 - 2020/11/16
N2 - While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.
AB - While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.
KW - blood biomarker
KW - brain injury
KW - concussion
KW - diffusion tensor imaging
KW - football
KW - neurite orientation dispersion and density imaging
KW - subconcussion
KW - youth
UR - https://www.scopus.com/pages/publications/85096920200
UR - https://www.scopus.com/pages/publications/85096920200#tab=citedBy
U2 - 10.3389/fneur.2020.581781
DO - 10.3389/fneur.2020.581781
M3 - Article
AN - SCOPUS:85096920200
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 581781
ER -