Spatiotemporal changes in diffusion,T₂and susceptibility of white matter following mild traumatic brain injury

Abstract

Impaired white matter integrity in traumatic brain injury (TBI) can lead to deficits in various neurological functions. Differentiation of the underlying pathological processes, e.g. edema, demyelination, axonal damage to name a few, is of key clinical interest for assessing white matter injury. In this study, a combination of T2, diffusion and susceptibility MRI were used to study the spatiotemporal changes in white matter at 1 hour, 3 hours, 1, 2, 7, and 14 days following TBI, using a rat controlled cortical impact (CCI) model. Based on radial diffusivity (RD), the rats were divided into two groups: group 1 showed widespread increases of RD along the corpus callosum of the ipsilesional hemisphere at day 2, and group 2 showed normal RD. Based on this group separation, group 1 also showed similar widespread changes of fractional anisotropy (FA) and T2 at day 2, and group 2 showed normal FA and T2. The widespread changes in RD and T2 in group 1 on day 2 were apparently dominated by edema, which obscured possible myelin and axonal damage. In contrast, the susceptibility of group 1 showed more localized increases near the impact site on day 2, and otherwise similar contrast to the contralesional hemisphere. The localized susceptibility increase is likely due to demyelination and axonal injury. The extent of brain damage between the two groups revealed by MRI was consistent with behavioral results where the first group showed significantly increased forelimb asymmetry and increased forelimb foot fault deficits. Our results suggest that the combination of T2, diffusion and susceptibility MRI may provide an opportunity for differential assessment of edema and axonal damage in TBI.

Combined Diffusion Tensor Imaging and Quantitative Susceptibility Mapping Discern Discrete Facets of White Matter Pathology Post-injury in the Rodent Brain

“…A study on rats in the CCI model found increased susceptibility at 2 days postinjury at the injury site as well as contralateral to the injury site in white matter which was similar to our susceptibility increase on day 1 and 3 post-injury. However, these changes were only found in the group of animals with higher radial diffusion in these areas, a finding contradictory to our TBSS results in Figure 1 (34). From the DTI results, they concluded oedema to dominate over axonal and myelin damage, followed by demyelination supported by their susceptibility findings 2 days post-injury.…”

“…Their average RD value started to increase after 3 days postinjury and remained high in the corpus callosum up to 1 month, the last time point studied. The increase in RD correlated with myelin damage, myelin loss, and gliosis in rodent TBI models (11,26,34). Increased RD without any noticeable change in AxD after 1-month in our study was similar to the findings of Song and colleagues in shiverer mice-demyelination, but no axonal injury or inflammation was detected in their model of retinal ischemia (19).…”

“…Interestingly, in R3 (see Figure 3), the region contralateral to the injury, we observed a change in susceptibility without pronounced changes in DTI measures. Li et al found a similar increase in white matter susceptibility in the group with increased RD based on a rat CCI model (34). Furthermore, they showed a correlation between increased susceptibility, demyelination, and increased RD.…”

“…QSM is a postprocessing technique which derives information from the gradient recalled echo MRI signal phase (i.e., phase image), and the signal magnitude (i.e., magnitude image), which may serve a number of purposes, including the creation of phase masks and structural priors within the image. The contrast in images generated using QSM has been associated with changes in the magnetic properties of the bulk tissue consequential of microscale changes in, for example, iron (haem/ non-haem), calcium, and myelin (32)(33)(34)(35). In the white matter, a decrease in phase image contrast is indicative of macro-and microhemorrhages or increased haem and non-haem iron content in tissue (36,37).…”

“…They did not find any differences between the methods, which may be explained by the low severity of the injury. Li et al combined QSM with DTI metrics in a rat controlled cortical impact (CCI) model (34). They observed increased susceptibility and RD in the demyelinating regions of the corpus callosum close to the injury site and reported QSM to be potentially more sensitive and specific to detect myelin changes near the injury site.…”