Dynamics of blood brain barrier permeability and tissue microstructure following controlled cortical impact injury in rat: A dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging study

Abstract

Objective: The blood-brain barrier (BBB) and cerebral tissue microstructure can be impaired following traumatic brain injury (TBI). However, the spatiotemporal changes of BBB leakage and tissue microstructure are not completely understood. In this study, we evaluated the spatiotemporal changes of BBB leakage and tissue microstructure using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in controlled cortical impact (CCI) rats.

Materials and methods: The DCE-MRI parameters volume transfer coefficient (K^trans) and DKI parameters were longitudinally measured in bilateral cortex, hippocampus, thalamus and corpus callosum (CC) at baseline (D0), acute stage (D1, D3), and subacute stage (D7, D14 and D28) post-injury. Immunohistochemistry analysis was performed at D28 after MRI scanning. Repeated-measures ANOVA was used to assess the temporal changes of MRI parameters.

Results: K^trans abnormality was only localized to ipsilateral perilesional cortex with a significant temporal change (F = 144.2, p < 0.0001). Compared to baseline, increased mean kurtosis (MK) was observed in ipsilateral regions of cortex and hippocampus and CC for all the time points (p < 0.05 for all). Increased MK was also observed in ipsilateral thalamus (p = 0.005) at subacute stage but not at acute stage while no change was observed with MD and FA (p > 0.05 for both). In ipsilateral cortex, the overall K^trans value of D0, D1, D3, D7, D14, and D28 post-injury were significantly correlated with MK value (r = 0.84, p < 0.0001). The CCI group showed higher staining of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) and lower staining of neuron-specific nuclear protein (NeuN) and myelin basic protein (MBP) in ipsilateral regions of cortex, hippocampus, thalamus and CC (p < 0.05 for all) as compared to control group. There were no significant differences in the contralateral regions by immunohistochemistry.

Conclusion: The BBB disruption reflected by K^trans correlated well with MK value in ipsilateral cortex. In addition, MK could detect the delayed microstructural changes in thalamus. DCE-MRI and DKI could be used to assess the BBB breakdown and cerebral microstructural changes of TBI.

Keywords: Blood-brain barrier; Diffusion kurtosis imaging; Dynamic contrast-enhanced MRI; Thalamus; Traumatic brain injury.