Spatial regression analysis of MR diffusion reveals subject-specific white matter changes associated with repetitive head impacts in contact sports

Abstract

Repetitive head impacts (RHI) are a growing concern due to their possible neurocognitive effects, with research showing a season of RHI produce white matter (WM) changes seen on neuroimaging. We conducted a secondary analysis of diffusion tensor imaging (DTI) data for 28 contact athletes to compare WM changes. We collected pre-season and post-season DTI scans for each subject, approximately 3 months apart. We collected helmet data for the athletes, which we correlated with DTI data. We adapted the SPatial REgression Analysis of DTI (SPREAD) algorithm to conduct subjectspecific longitudinal DTI analysis, and developed global inferential tools using functional norms and a novel robust p value combination test. At the individual level, most detected injured regions (93.3%) were associated with decreased FA values. Using meta-analysis techniques to combine injured regions across subjects, we found the combined injured region at the group level occupied the entire WM skeleton, suggesting the WM damage location is subject-specific. Several subject-specific functional summaries of SPREAD-detected WM change, e.g., the L ∞ norm, significantly correlated with helmet impact measures, e.g. cumulative unweighted rotational acceleration (adjusted p = 0.0049), time between hits rotational acceleration (adjusted p value 0.0101), and time until DTI rotational acceleration (adjusted p = 0.0084), suggesting RHIs lead to WM changes. Sport-related concussions and repetitive head impacts (RHI) incurred during sports have emerged as important foci of brain injury research with the increased awareness and improved understanding of these injuries' effects on neurocognitive function. RHI are broadly defined as any direct or indirect hit that exerts a force on the brain that may or may not cause a clinically diagnosed concussion 1. RHI occur frequently during contact and collision sports at all levels of play including youth, collegiate, and professional competitions. Both animal and human studies have shown acute changes in brain structure and function after RHI that are indicative of axonal injury 2-10. This understanding of the acute impact on the brain has led to questions about RHI's potential long-term neurocognitive effects. The direct connection between RHIs, acute brain injury, and their possible long-term effects on brain structure and neurocognitive function are difficult to confirm with retrospective research. Montenigro and colleagues showed a retrospective survey metric for head impact exposure was strongly associated with behavioral and cognitive dysfunction later in life 1. In addition, post-mortem studies of chronic traumatic encephalopathy (CTE) have described RHI as a necessary but not sufficient risk factor, which suggests RHI lead to biologic dysregulation and clinical symptoms 11. Despite this retrospective evidence, RHI causing CTE and other neurodegenerative

Identifying relevant diffusion MRI microstructure biomarkers relating to exposure to repeated head impacts in contact sport athletes

“…Of note, for the top 2 classifiers, FA was not found to be especially informative despite prior reports associating FA changes with RHI 1,6,7,8,9,10,11,12 , (Figure 2). This may relate to known time-dependence of FA changes after injuries 34 : FA has been documented to change from elevated in the acute stage after MTBI to decreased in more chronic stages.…”

“…This may be due to the inherent heterogeneity of RHI in terms of location. 12 All 7 ROIs show similar importance for the classification task, suggesting that the effects of RHI may be heterogeneous across individuals. Our finding is consistent with prior studies where various different brain regions have independently been associated with WM alterations relating to RHI.…”

“…4 Diffusion MRI has been used to study the in vivo changes to brain microstructure after RHI. 1,5,6,7,8,9,10,11,12 With published studies relying almost uniformly on conventional statistical methods to analyze group-level differences of individual diffusion metrics separately such as fractional anisotropy (FA), 1,6,7,8,9,10,11,12 mean diffusivity (MD), 1,6,7,8,9 and mean kurtosis (MK). 10, 11 With advances in non-Gaussian approaches and compartment modeling of diffusion signal, our ability to characterize biophysical characteristics of white matter has progressed; however, as a result, diffusion MRI has become ever more challenging to interpret because of the sheer variety and number of metrics (both empiric and modeled) that can be used.…”

Analisis Determinan Kemiskinan Di Pulau Jawa Dengan Model Regresi Spasial

“…Hal ini akan menyebabkan asumsi kebebasan antar pengamatan dalam analisis regresi sulit terpenuhi. Asselin et al (2020) menjelaskan apabila model regresi klasik digunakan sebagai alat analisis pada data spasial, maka bisa menyebabkan kesimpulan yang kurang tepat karena unsur spasial tidak tercakup.…”

Glymphatic system impairment in nonathlete older male adults who played contact sports in their youth associated with cognitive decline: A diffusion tensor image analysis along the perivascular space study

“…Contact sports have been linked to neurocognitive changes due to repetitive head impacts (RHIs) ( 1 – 3 ). RHIs refer not only to mild traumatic brain injury and concussion but also to asymptomatic subconcussive trauma ( 4 , 5 ). RHIs in contact sports are quite frequent, with up to 3–70 head impacts per game that players were exposed to, depending on the sport ( 6 , 7 ).…”