Prognostic Value Of Resting-state FMRI Combined With Copeptin In Coma Patients With Traumatic Brain Injury

Objective: Traumatic Brain Injury(TBI)is a major public health concern.Among the patients with TBI impaired consciousness,the prognosis is a major clinical challenge.Therefore,assessing the prognosis of patients with TBI coma(wake up,coma,or death)has extremely important clinical guidance and social value.This study is based on the Default Mode Network(DMN)and Executive Control Network(ECN)to explore the difference in severe TBI patients with different prognosis on early(7 to 28 days)functional connectivity(FC),and explain the neural mechanism of its change and propose potential imaging biomarkers.In addition,plasma copeptin are also important biomarkers reflecting brain injury.This study further evaluate the FC intensity values of characteristic brain regions combined with plasma copeptin concentrations in the prognostic assessment of patients with severe TBI.Methods: According to the pre-established inclusion and exclusion criteria,patients with severe TBI,admitted to the Department of Neurosurgery,Subei People’s Hospital in Jiangsu Province from July 2019 to July 2020,were consecutively recruited.We collected the characteristic data of the included subjects and data of the plasma copeptin concentrations and resting functional magnetic resonance imaging(f MRI)from 7 to 28 days after injury(the time of data collection for healthy controls was not limited).According to the extended Glasgow outcome score(GOS-E)after 3-6 months,the patients were divided into awakening,coma and death groups.The software SPM 12 and Rest 1.8 were applied to pre-process and post-process the f MRI data.The software Rest 1.8 was used to perform a two-sample t-test to compare the difference of FC in the brain regions of patients with severe TBI and healthy controls,compare the difference in FC between patients with awakening after 3-6 months and those in coma after 3-6months,and compare the difference in FC between patients with coma after 3-6 months and those in death after 3-6 months.False discovery rate(FDR)was used for correction,and P < 0.05 after correction was defined as statistically significant.The calculated brain region map will be mapped to the standard template,by Mango and Brainnet review software.Based on the software Rest 1.8,the FC intensity value of the characteristic brain regions and posterior cingulate cortex(PCC),called the Z value,were extracted.The software SPSS 23.0 was applied for continuous and dichotomous data analysis.In addition,the diagnostic potency of FC intensity value and copeptin for prognostic analysis in patient with severe TBI is expressed by the receiver operating characteristic curve(ROC)and the area under curve(AUC).Results: According to the inclusive,exclusive and matching criteria,the 20 patients were included in the experimental groups(severe TBI groups),and the age distribution was 18-79 years old(median 62.5).In the healthy controls,15 cases were included in the analysis,and the age distribution was 26-73 years old(median 61).Baseline data between groups: age,years of education,gender,right-handed situation and past history were not statistically significant(P > 0.05).The findings of the study indicated that: 1)Compared with healthy controls,FC in patients with severe TBI had different degrees of increased [PCC as the region of interest(ROI)] or weakened [with PCC or dorsolateral prefrontal cortex(DLPFC)as ROI];2)Compared with the coma patients after 3-6months,the FC of the awakening groups after 3-6 months had different degrees of enhancement(PCC or DLPFC as ROI);3)Compared with the death groups after 3-6months,the FC of the coma patients after 3-6 months had different degrees of enhancement(PCC or DLPFC as ROI);4)The FC intensity of the central anterior gyrus,PCC,and upper frontal gyrus and copeptin were complementary to achieve a good prediction of the prognosis(wake up,coma and death)of patients with severe TBI after3-6 months.The FC intensity of copeptin combined with the central anterior gyrus had the strongest ability to predict the waking of severe TBI patients after 3-6 months,and its AUC was 0.958.The FC intensity of PCC had the obvious ability to assess the coma after 3-6 months of severe TBI patients,with an AUC value of 0.820.Moreover,the combination of PCC’s FC intensity and copeptin were the best protocol to predict the death of severe TBI patients after 3-6 months,and the titer was 0.847.Conclusions: In severe TBI patients with different prognosis,there are differences in the early(7-28 days)brain region FC.The discovery of this difference provides a theoretical basis for future intervention studies on characteristic FC altered brain regions,which could be used as a potential target for wake-up treatment.In addition,the copeptin combined with FC intensity in characteristic DMN brain regions have significant clinical application value in the early assessment of the prognosis of patients with severe TBI.However,the conclusions are limited by sample size and single-center and their validity needs further clarification.