MRE elastography-based detection of impaired skull-brain decoupling after repetitive subconcussive sports impact

PROJECT SUMMARY/ ABSTRACT Repetitive subconcussive head impacts (RHI) in contact sports are gaining attention, with prolonged exposure linked to chronic traumatic encephalopathy and cognitive decline. Since RHI is often asymptomatic in the early stages, there is an unmet need for early detection of RHI-induced impairments. In our previous grant cycle, we focused on the function of connected anatomic interfaces, particularly the skull-brain (SB) interface (which has evolved to isolate the brain from impact) and its early impairments due to RHI. We developed noninvasive harmonic MR elastography (MRE)-based imaging markers to quantify SB mechanical decoupling, providing the first evidence of early SB impairment in individuals with a history of asymptomatic RHI. We hypothesize that RHI exposure alters the viscoelastic properties of the pia-arachnoid complex through repeated injury and healing. This impairment increased with longer RHI exposure and decreased with longer intervals after exposure, suggesting individual variability in the progression and repair of SB impairments. Other research also indicates that brain injury severity varies significantly due to increased vulnerability from prior RHI exposure or inherent factors. These findings highlight the need for further research into individual SB mechanical vulnerabilities (SBMV) and the longitudinal effects of RHI, which is the focus of this renewal grant. While harmonic MRE metrics developed in the prior grant cycle can assess SB decoupling at equilibrium and track longitudinal changes from RHI, they may be less suitable for evaluating pre-existing individual SBMVs. The risk of SB interface impairments or injury is hypothesized to be linked to spatial and temporal variations in SB interface responses to real-life transient impacts, like existing research on brain injury risk predictions. However, as illustrated in our preliminary data, harmonic MRE, which focuses on equilibrium vibration states, fails to detect regional variations in cortical responses, which are revealed by transient MRE. Advancing from harmonic to transient MRE is thus crucial for identifying SBMV, as transient MRE provides critical in vivo measures of high-risk SB interface areas under low impact levels, with these regions likely remaining at risk or worsening under higher impacts, presumably linking to SB decoupling variability in RHI outcomes. In this renewal, Aim 1 addresses the technical challenge of implementing and validating a new transient MRE method to efficiently characterize impulse responses. In Aim 2, we will build individualized SBMV maps and study age/sex effects. In Aim 3, we will integrate harmonic and transient MRE in a longitudinal sports study, with two goals: 1) detect post-season equilibrium SB decoupling changes, and 2) link the likelihood of these changes to pre- season SBMV. Our hypotheses are: 1) post-impact mechanical alterations occur at the SB interface, and 2) these alterations are related to pre-existing SBMV. We will also correlate MRE metrics with diffusion and cognitive function for outcome predictions. Ultimately, this project aims to develop an imaging approach to identify individuals at high risk for SB decoupling impairment from RHI, enabling targeted mitigation and recovery monitoring.