Multimodal FMRI Study On The Assessment Of The Rehabilitation Effect Of Hyperbaric Oxygen On The Mild Traumatic Brain Injury

Objective: Hyperbaric oxygen(HBO)treatment has been widely used in nerve injury disease,gradually becoming an important adjuvant treatment method after brain trauma.However,due to lack of effective imaging markers for the clinical diagnosis,patients with mild traumatic brain injury(mTBI),the rehabilitation effect of HBO therapy on the brain function and structure is still unclear.This paper is aimed to investigate the changes in neural activity using amplitude of low frequency fluctuation(ALFF)based resting state BOLD-fMRI technology,the changes of diffusion tensor of whole brain white matter fiber skeleton using Tract-based spatial statistics(TBSS)technology,the improvement of cerebral blood flow(CBF)using 3D-ASL technology after HBO rehabilitation treatment.Combining multimodal image data,the present study is aimed to provide a potential imaging biomarkers for the evaluation for the effect of HBO rehabilitation treatment.Materials and methods: The present study has recruited in 40 patients with mTBI(21 cases of male,female 19 cases,average age 35±8.5 years)hospitalized in the PLA 180 hospital during the period of September 2012 to September 2016.Male and female participants were randomly divided into hyperbaric oxygen group(HBO group)andmTBIgroup without hyperbaric oxygen treatment.HBO group included 20 participants,with 11 male cases,9 female cases,average age 34.0±4.98.MTBI group included 20 participants,with 10 male cases,10 female cases,average age 36.2±8.97.Additionally,22 healthy volunteers of normal controls(NC group)were recruited with demographic data,such as sex,right-handed,age and level of education matched with patients with mTBI,including 10 male cases and12 female cases,average age 32.3±6.6 years old.Using Siemens Skyra 3.0 T superconducting MRI scanner,we performed all routine scan sequences,such as T1 WI,T2WI and T2-FLAIR,to eliminate the head organic disease patients.And then we collected BOLD resting state fMRI and DTI and 3 d-ASL images,respectively calculating BOLD functional images,DTI images and CBF images.Toolboxes including SPM8 / REST1.8,FSL 4.1.7 and ASLtbx were involved in the original image preprocessing,and calculations of whole brain ALFF value,white skeleton FA/MD and whole brain CBF value of each group.Using one way analysis of variance,,this paper compares images in three groups and analyzes brain regions with significant group effect.Furthermore,the brain regions with significant group effect were picked as regions of interest(ROI)saving as masks.The ALFF,CBF values of each group in the masks were extracted for between-group comparisons.Using SPSS19 software,ALFF and CBF values were compared.Results:(1)Results about resting-state ALFF: ALFF in regions including right medial prefrontal cortex,insula and parietal lobe showed significant groups differences.Specifically,these regions were included: the left middle/inferior temporal gyrus,right middle/superior temporal gyrus,right insula and surrounding subcortical structure,the medial prefrontal cortex,the right medial superior frontal gyrus,right inferior/superior parietal lobe,precuneus,left supplementary motor area(paracentral lobular).Post hoc pairwise comparison showed that ALFF values in these ROIs of mTBI group have significant differences with NC group,while ALFF values of HBO group after hyperbaric oxygen therapy in the medial prefrontal cortex and the supplementary motor area and right parietal lobe were significantly improved,showing no significant difference compared with NC group,but significantly higher than the untreated mTBI group.And ALFF values in the right temporal lobe,insula,medial superior frontal gyrus and left temporal lobe showed no significant difference between HBO group andmTBI group,but significantly lower than normal group.(2)Results about TBSS analysis: Compared with NC group,the FA values in the mTBI group,were significantly decreased under the joint in front of the corpus callosum,bilateral longitudinal fasciculus,right longitudinal fasciculus.Whereas the MD valuesshowed higher in the whole brain white matter,mainly focused in the left corpus callosum,the rear part of the corpus callosum,bilateral corticospinal tract,white matter in the right frontal lobe,etc.Compared with NC group,FA values in the HBO group after hyperbaric oxygen therapy showed no significantly reduced,reflecting improved rehabilitation effect.The MD value in some areas still showed higher,mainly focused in bilateral internal capsule,corpus callosum,pons,at the back of the white matter,etc.but the abnormal area was significantly reduced compared with mTBI group.(3)Results about resting state CBF: CBF values in the three groupswithsignificant positively effectswere mainly located in parietal-occipital cortex,including the bilateral parietal lobe,precuneus,posterior cingulate cortex,supramarginal gyrus,and the fusiform gyrus,as well as in the anterior cingulate cortex.While significant negative effects of brain regions,were mainly in the fronto-parietal area,temporal lobe and the midbrain regions,including bilateral dorsolateral frontal in inferior frontal gyrus,bilateral medial frontal cortex,bilateral parahippocampal gyrus and the amygdala,the left putamen and caudate nucleus,the midbrain,the right lingual gyrus,right inferior occipital gyrus,bilateral inferior parietal lobe and left precentral/postcentralgyrus.Post hoc comparisons showed that the HBO group had significantly improved CBF in the bilateral superior parietal lobe,anterior cingulate cortex and posterior cingulate cortex,significantly differed from mTBI group,but still significantly differed with NC group.CBF values in themTBI group after HBO treatment got significant recoveryin the dorsolateral prefrontal and inferior parietallobe,significantly higher than the mTBI group,and no significant difference from the NC group.In the medial prefrontal cortex,midbrain,lingual gyrus,the inferior occipital gyrus,CBF values in the HBO group were still significantly lower than that of NC group,but no significant difference with the mTBI group.(4)Results about multimodal imaging correlation analysis: The CBF and ALFF values of the HBO group showed significant positive correlation in the frontal dorsolateral prefrontal(r = 0.658,P = 0.658),and the medial prefrontal(r = 0.72,P = 0.72).But no correlations were found in other areas.DTI parameters were found no significant correlation with the CBF and ALFF.Conclusion: The present study showed that the hyperbaric oxygen therapy has a positive rehabilitation effect on the brain function and structure.The HBO showed regional selective rehabilitation for improving the parameters of ALFF,FA/MD and CBF,with promoting effect on part of the brain regions,while no obvious improvement for other brain regions.Multimodal imaging correlation analysis results showed that the promoting effect of HBO therapy provided more influence on complex cognitive task oriented dorsolateral frontal,the medial prefrontal cortex and other brain function recovery through neural tissue repair and neuron activity plasticity and other process.