| Objective To establish rotational traumatic brain injury(TBI)models of rabbit heads,observe and study dynamic laws in early stage post injury by DTI and DKI functional magnetic resonance imaging(fMRI)integrated with neurological severity score(NSS)and pathological changes in its evaluation,and explore clinical significance of new fMRI techniques in detecting and assessing TBI earier.Materials and Methods 15 healthy New Zealand rabbits aging 6 month-old were randomly divided into control group(n=3)and injured group(n=12)preformed on an autonomous rapid-rotational injury device to built models.Observation in behavior disorders and NSS scores were carried out on the later group.Routine MRI,DTI and DKI were performed on the injured group respectively in superacute phase(6h),acute phase(24h and 48h),and prophase of subacute phase(72h),totally 3 injured phases and 4 programmed periods(3 rabbits per subgroup).Ethological observation and NSS assessment were conducted in the control group right before MR scan.Animals of each group were executed immediately post MR scan whose brains were taken,fixed,embedded,and sampled.HE staining and ?-amyloid precursor protein(?-APP)immunohistochemical staining were operated.Region of interest(ROI)were settled in subcortical white matter,thalamus,midbrain,pons and medulla oblongata of animal models.FA,ADC,MK?K//,and K? values were measured.The number of ?-APP positive axons per 5×400 high power fields were counted and averaged while observing pathological sections dyed by HE or ?-APP stain.NSS scores of different time in injured group were compared by One-way ANOVA.Kruskal Wallis Test was conducted to analyze FA,ADC,MK,K// and K? values in each measured brain region separately,which in injured group were compared with that in control by two independent samples rank sum test.One-way ANOVA was applied in compare of the number of ?-APP positive axons in brain region separately at each time point,which in injured group were compared with that in control by least significant difference t-test(LSD-t test).Correlations between the number of ?-APP positive axons in each brain area and FA?ADC?MK?K//?K? values or NSS scores were analyzed by Spearman correlation analysis.P<0.05 was considered statistically significant.Results 1.TBI rabbits presented behavioral abnormalities to varying degrees,NSS scored(2.733±1.831).No significant statistical difference was found among different time points(F=1.878,P=0.191).One rabbit occasionally died because of poor fixation on its neck,which was then supplemented successfully.The success rate of model establishment was 92.3%(12/13).2.ADC values showed the trend of transient decrease and then increase before decrease again.In superacute phase(6h),except of subcortical white matter,ADC values were slightly reduced in all the other measured areas,which reach at the peak at 48 h and then declined gradually.ADC values tended to decrease compared with the control in most of the brain regions instead of pons and medulla oblongata in prophase of subacute phase(72h)(P<0.001).3.FA values featured rise temporarily and then decrease before increase again.Most of the brain regions(subcortical white matter,midbrain,pons and medulla oblongata)showed higher FA values compared with that before injury(P<0.05),which reduced during acute phase(24~48h).At the time point of prophase of subacute phase(72h),FA values increased in subcortical white matter and thalamus(P<0.001),while decreased in brainstem(P<0.001).4.Different brain regions indicated diverse tends in MK values.It rose transiently at 6h and then continuously decreased in subcortical white matter(P<0.05),which slightly reduced at 6h post injury in thalamus and then gradually increase(P<0.05),while showed sustaining increase in brainstem areas which reached at the peak at 72h(P<0.05)post injury.5.Variation of K// and K? values demonstrated similar trends,namely increasing in 24 h after injury,and then decrease to diverse degrees before continuously rising(P<0.05).K// and K? values in midbrain showed different trends.K// values increased in superacute phase and then slightly decrease,which continuously rose after 24 h,whlie K? values sustainably increased in 24 h,which mildly decreased for the moment and then increase little by little(P<0.05).In pons medulla oblongata K// and K? values were persistently higher than that in the control(P<0.05).6.Number of ?-APP positive axons in most of the observed brain regions(subcortical white matter,midbrain,pons and medulla oblongata)indicated positive correlation with NSS scores(P<0.05),especially in brainstem(r>0.05,P<0.05).7.Negative relationship was found between FA values and number of ?-APP positive axons in midbrain(r=-0.432,P=0.019),which was positive correlated to ADC values in pons and medulla oblongata(r=0.558,P=0.010),while no obvious statistical relationship was found in other measured regions between FA or ADC values and number of ?-APP positive axons(P>0.05).Except of thalamus,MK values in were positively correlated with number of ?-APP positive axons in other measured areas(P<0.05),particularly obvious in brainstem(r>0.5,P<0.05).K// and K? values in brainstem were significant positive related with number of ?-APP positive axons(r>0.5,P<0.05).Conclusions The rotational TBI model applied in this research is able to simulate its pathological mechanism,which is effective in establishing the model with good stability and repeatability.Observation of mTBI animals by DTI indecated that FA and ADC values changed dynamically with contrary trends and biphasic variation,which were helpful in distinguishing cytotoxic edema and vasogenic edema.Observation of mTBI animals by DKI indicated that MK,K // and K ? values varied by time,which showed more significant relationship with the number of ?-APP positive axons than FA and ADC values.DKI is more sensitive in assessing TBI than DTI,which is contribute to understanding the complexity of microstructural damage post TBI and is important and meaningful in comprehending its pathological evolvement rule. |
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