Noninvasive mapping of shear strain predicts the anatomical distribution of mild traumatic brain injury

Shear strain has been implicated as a key factor driving tissue injury in traumatic brain injury (TBI) (Holbourn, 1943; Ommaya et al., 1994; Margulies et al., 1990), but evidence has been lacking that links in vivo measures of strain in the human brain to the distribution of structural damage observed in TBI. In this study, we investigated the relation between strain concentration, measured using Magnetic Resonance Elastography (MRE), and changes in structural integrity, measured using Apparent Fiber Density (AFD), in mild TBI (mTBI) patients. We use MRE to show that regions commonly associated with differential brain tissue damage - such as the midbrain, cerebellum, mesial temporal lobe, and the interface between the cortex and white matter at sulcal depths as well as the corpus callosum (McKee and Daneshvar, 2015; Weiner et al., 2014; Weiner et al., 2017; Tomaiuolo et al., 2004; Maxwell et al., 2006; Hirad et al., 2019; Blecher et al., 2019; Bartsch and Deuschl, 2010; Smith et al., 1997; Ross et al., 1993; Zimmerman et al., 2023; Ghajari et al., 2017) - are also sites of biomechanical vulnerability due to shear strain concentration in healthy participants. We then found that the regions that exhibit high strain, measured with MRE in healthy participants, are the sites of greatest injury, as measured with diffusion MR in acute, sub-acute, and chronic mTBI patients. These findings provide in vivo evidence in humans that brain structures differentially vulnerable to high biomechanical strain from skull force loading also exhibit disrupted tissue integrity across the acute, sub-acute, and chronic phases of mTBI recovery. Follow on analyses demonstrate that strain concentration in those regions results from both the differential focusing of impact energy as well as inadequate energy dissipation.