Dynamic Contrast-enhanced Magnetic Resonance Imaging Combined With Diffusion Kurtosis Imaging In Assessment Of Cerebral Structural And Cognitive Alterations After Mild Traumatic Brain Injury

Background:Cognitive defect is one of the common sequelae of mild traumatic brain injury(mTBI).However,the clinical evaluation of mTBI in the prediction of cognitive dysfunction is limited.Blood-brain barrier(BBB)breakdown and cerebral microstructural changes post-injury correlated with cognitive dysfunction.Dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and diffusion kurtosis imaging(DKI)could be used to characterize the BBB permeability and cerebral microstructural alterations.Therefore,we aim to investigate the value of DCE-MRI combined with DKI in the assessment of early microstructural changes and chronic cognitive function after mTBIObjective:(1)We aim to evaluate 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.(2)We aim to explore the value of early DKI and DCE-MRI in evaluation of chronic cognitive function after mTBI Materials and methods:(1)Firstly,eight adult male Sprague-Dawley rats were subjected to CCI injury.Three additional control rats without impact intervention were included.The DCE-MRI parameters volume transfer coefficient(Ktrans)and DKI parameters were longitudinally measured in bilateral cortex,hippocampus,thalamus and corpus callosum(CC)at baseline(DO),acute stage(D1,D3),and subacute stage(D7,D14 and D28)post-injury Immunohistochemistry(IHC)analysis was performed at D28 after MRI scanning.Repeated-measures ANOVA was used to assess the temporal changes of MRI parameters.(2)Secondly,sixteen adult male SD rats were randomly assigned into two subgroups:1)TBI(n=8);2)Control(n=8).DKI and DCE-MRI were performed on TBI and control rats at D7 post-injury MRI parameters were measured in bilateral cortex,hippocampus,thalamus and CC.All the rats underwent Morris water maze(MWM)at 6 months after injury.IHC analysis of neuron[NeuN],astroglia[GFAP],microglia[Iba-1],and myelin[MBP]was performed after the MWM testResults:(1)In the TBI group,Ktrans 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 Ktrans value of D0,D1,D3,D7,D14,and D28 post-injury were significantly correlated with MK value(r=0.84,p<0.0001)The TBI 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.(2)TBI group showed increased Ktrans value in ipsilateral cortex(p<0.0001)and no detectable changes in other regions-of-interest(ROIs),compared with control group.DKI showed higher MK in all ipsilateral ROIs(p<0.05),higher MD in ipsilateral cortex,hippocampus and CC(p<0.05)in TBI group.TBI group had worse performance in MWM test at 6-months post-injury.IHC analysis showed lower NeuN,and higher GFAP and Iba-1 in all ipsilateral ROIs(p<0.05)in TBI rats.NeuN,GFAP,Iba-1 and MBP correlated significantly with MK value in ipsilateral regions of cortex and hippocampus and CC.The MK value of ipsilateral cortex,hippocampus and CC and Ktrans value of ipsilateral cortex also correlated significantly with time in the target quadrantConclusion:(1)The BBB disruption reflected by Ktrans 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 mTBI.(2)Early quantitative MRI parameters significantly correlated with long-term cognitive dysfunction.DKI and DCE-MRI can be used to detect early cerebral damage,and could indicate chronic cognitive outcome following mTBI.