The Value Of 3D-T1WI Sequence And DKI Sequence In The Assessment Of Cognitive Impairment After TBI

Background: At present,the pathological mechanism leading to cognitive impairment after Traumatic brain injury(TBI)is still not fully understood.Magnetic Resonance Imaging(MRI),especially the 3D-T1 WI sequence and Diffusion kurtosis imaging(DKI)sequence,play an increasingly important role in assessing brain structural pathological changes.This project mainly focuses on investigating the value of 3D-T1 WI sequence and DKI sequence in the assessment of cognitive impairment after TBI.Objective:(1)To investigate the brain structural changes in sub-acute mild traumatic brain injury(m TBI)using DKI technique and volumetric analysis,and to assess the relationship between brain structural changes and cognitive function.(2)To investigate whether self-reported mild TBI was associated with decreased AD-vulnerable cortical thickness,and to assess the relationship between AD-vulnerable cortical thickness and AD-related biomarker in the Alzheimer’s disease Neuroimaging Initiative subjects.(3)To assess the longitudinal brain microstructural changes in TBI rat using DKI.(4)To investigate the value of DKI in the assessment of microstructural changes and cognitive impairment in chronic TBI rat.Materials and methods:(1)Firstly,a total of 23 m TBI patients in sub-acute stage and 24 control participants were recruited in this study.All the participants underwent examinations of neuropsychological tests,MRI-based morphological and DKI scans.Images were investigated using whole brain-based analysis and further regions of-interest-based analysis for subcortical nuclei.(2)Secondly,we identified 45self-reported m TBI subjects,who had structural MRI,18F-AV45 PET,and cerebrospinal fluid(CSF)data.Additional demographics-controlled 45 subjects were included.Cortical thickness of eight AD-vulnerable regions,mean AD-vulnerable cortical thickness,AD-related biomarkers were compared between m TBI and non-TBI groups.Correlational analysis was done to investigate the relationship between mean AD-vulnerable cortical thickness and AD-related biomarkers.(3)Thirdly,DKI was performed in a group of 5 rats at pre-injury,3 day,14 day and 28 day after TBI.The DKI parameters were measured in bilateral cortex,hippocampus,and callosum.Another four groups of 5 rats were used for brain Immunohistochemistry(IHC)analysis of neuron(Neu N),astroglia(GFAP),microglia(Iba-1),and myelin(MBP)in the same area to DKI parameter measurement.Furthermore,two groups of 6 rats underwent a Morris water maze(MWM)test at 28 day after TBI.The DKI parameters,IHC results,and MWM test results were compared longitudinally or between TBI and control group.(4)Fourthly,six TBI rats and six control rats were included.At seven months after TBI,all the rats underwent a Morris water maze(MWM)test,followed by an MRI-based DKI examination.The DKI parameters were measured in bilateral cortex,hippocampus,and callosum.Then,all the rats were harvested for brain Immunohistochemistry(IHC)analysis of neuron(Neu N),astroglia(GFAP),microglia(Iba-1),and myelin(MBP)in the same area to DKI parameter measurement.The DKI parameters,IHC results,and MWM test results were compared between TBI and control group.Correlation analysis was performed to analyze the relationship between DKI parameters and IHC,MWM results.Results:(1)m TBI patients showed higher mean kurtosis(MK)in widespread white matter(WM)regions and several subcortical nuclei(P<0.05).The MK value of multiple WM regions and several subcortical nuclei was positively correlated with cognitive function(P<0.05).(2)Preclinical AD subjects with self-reported m TBI had smaller cortical thickness in mean and three AD-vulnerable cortical regions than non-TBI subjects(P<0.05).The mean AD-vulnerable cortical thickness was correlated with CSF T-tau(P<0.05).(3)Compared with baseline,the TBI rat at all three time points had higher mean kurtosis(MK),higher mean diffusion(MD)value in ipsilateral perilesional cortex and hippocampus,lower fractional anisotropy(FA)value in callosum(P<0.05).And the TBI group showed higher staining of GFAP and Iba-1,and lower IHC staining of Neu N and MBP in all ipsilateral ROIs(P<0.05).The MWM test revealed lower platform crossing times in the probe test at 28 day after TBI(P<0.05).(4)DKI revealed higher mean diffusion(MD)value in all ipsilateral ROIs,lower mean kurtosis(MK)value in ipsilateral perilesional cortex and callosum in TBI group(P<0.05).The TBI group also showed lower IHC staining of Neu N,and higher staining of Iba-1 and MBP in all ipsilateral ROIs(P<0.05).Further correlational study revealed positive relationship between MK and Neu N,MD and MBP in ipsilateral perilesional cortex,and negative relationship between MK and Iba-1,MBP in ipsilateral perilesional cortex and hippocampus(P<0.05).The MK in ipsilateral perilesional cortex and hippocampus were also correlated with MWM test results(P<0.05).Conclusions:(1)DKI was sensitive to detect brain microstructural changes in sub-acute m TBI showing higher MK value in widespread WM regions and several subcortical nuclei,which were statistically associated with cognitive deficits.(2)Our study indicated that among individuals with preclinical AD,but not normal,MCI due to AD and AD subjects,self-reported m TBI was associated with more decreased AD-vulnerable cortical thickness which was related to CSF tau pathology,suggesting the possible early involvement of tau pathology in the decreased AD-vulnerable cortical thickness of self-reported TBI subjects.(3)There were longitudinal changes in DKI parameters,accompanied by multiple pathological changes at different time points following TBI.MK was more sensitive to detect brain microstructural changes than MD and FA,especially in grey matter.(4)The chronic TBI rat also had multiple pathological changes and cognitive impairment.DKI parameters correlated with IHC staining indicative of neuron loss,microgliosis,and myelin disruption.DKI could be used to the assessment of cognitive impairment after chronic TBI.