Multimodality Magnetic Resonance Imaging Of Brain Metabolites And Neural Functional Networks In Patients With Acute Carbon Monoxide Poisoning

Purpose:Magnetic Resonance Spectroscopy(MRS),Glutamate Chemical Exchange Saturation Transfer imaging(Glu CEST)and resting functional MRI(r-f MRI)was used in this study to assess the changes of metabolites,dynamic Functional Network Connectivity(d FNC)and brain network topology between subjects with acute CO poisoning and healthy volunteers.In order to further explore the imaging changes of brain injury in the early stage of acute CO poisoning,the remodeling process of brain network in patients with CO poisoning and the changes of metabolites in micromolecules were explored,providing an objective and effective basis for clinical evaluation and prognosis prediction of patients with acute CO poisoning.Material and Method:A total of 29 clinically diagnosed acute CO poisoning patients and 29 healthy controls were collected.Meanwhile,they were divided according to age into adult CO poisoning group and control group,and children CO poisoning group and control group.All the participants received routine MRI examination,MRS examination,Glu CEST,f MRI and Mini-mental State Examina Scale(MMSE)within 3 days after admission,and were followed up by using Hamilton Anxiety Scale(HAMA)within 3 months of discharge.1.MRS:MRS data were processed by LCModel software,and choline(Cho),Glutamate(Glu),Gamma-aminobutyric acid(GABA)and Glutamin(Gln)of bilateral frontal lobes,globus pallidus,occipital lobe and thalamus were collected respectively.The correlation between the absolute concentration of each MRS metabolites and clinical indicators was analyzed.2.Glu CEST:Glu CEST % values of bilateral globus pallidus,thalamus,knee of corpus callosum,frontal lobe,occipital lobe,cuneus and cingulate gyrus were collected after processing Glu CEST raw data with Matlab software.The correlation between Glu concentration and clinical indicators in each region of interest was analyzed.3.The f MRI analysis was divided into two parts: graph theory and dynamic brain network functional connection(d FNC).A.The original f MRI data of graph theory were preprocessed by GRETNA software to construct the brain functional network.The global and regional network indicators of the brain network are calculated respectively.The global parameters include small-world parameters(clustering coefficient Cp,normalized clustering coefficient γ,normalized characteristic path length λ,characteristic path length Lp,small-world attribute index σ)and network efficiency parameters(local efficiency Eloc and global efficiency Eglob).Node characteristics are evaluated by node network parameters such as node degree,node centrality and node efficiency.When significant differences in network indicators were found between groups,correlation analysis was conducted between these indicators and clinical indicators of the CO poisoning group.B.The original f MRI data of dynamic functional connection were preprocessed by RESTplus software and then GIFT software was used to establish the internal connection network.According to the corresponding anatomical location and their functional characteristics,51 internal networks of all subjects were independently divided into the following 7 functional networks: basal ganglia network BG;Auditory network AUD;Sensorimotor network SM;Visual network VIS;Cognitive executive network CEN;Default network DMN;Network cerebellum CB.All d FNC windows for each subject were divided into four states based on their similarity to the four cluster centers.Three different metrics were used to evaluated the time and intensity characteristics of dynamic functional connectivity state,including the mean dwell time,fractional window,and the number of transitions.The correlation analysis was conducted between dynamic functional network connectivity indicators and clinical indicators in the acute CO poisoning group.Results:There was no significant difference in age and gender between the acute CO poisoning group and the control group.Compared with the healthy control group,the MMSE score of CO poisoning group was lower,and the difference was statistically significant(p <0.01).There was no statistical difference in HAMA scores during follow-up between the control group and acute CO poisoning group.1.MRS:Compared with control group,the Gln concentrations in the globus pallidus,thalamus and occipital lobe of acute CO poisoning patients were increased(p <0.01).The Glu concentrations in globus pallidus of CO poisoning group patients were also increased.(p <0.05).Compared with adult healthy volunteers,the GABA concentrations in globus pallidus of adult acute CO poisoning group was decreased(p <0.01),while the Gln,Glu and Cho in globus pallidus were increased(p <0.05).The Gln concentrations in thalamus and occipital lobe of aldult CO poisoning patients were increased(p <0.05).Compared with the children healthy volunteers,the Gln concentrations of thalamus was increased and Cho concentrations of occipital lobe in children CO poisoning group was decreased(p <0.05).The Glu concentrations in the globus pallidus of adults with CO poisoning was increased and negatively correlated with COHb%,while there was no statistical difference the concentrations of other metabolites with clinical indicators.2.Glu CEST:The GLUCEST% values in CO poisoning group were generally increased compared with control group.The GLUCEST% values in globus pallidus,occipital lobe,genu of the corpus callosum,cingulate gyrus and cuneus of acute CO poisoning patients were increased(p <0.05).Compared with the adult healthy volunteers,GLUCEST % values in globus pallidus,thalamus,occipital lobe,cingulate gyrus and cuneus were increased in adult acute CO poisoning group(p <0.05).Compared with the children control group,GLUCEST % values in multiple ROIs in the children CO poisoning group was increased,but no statistical difference was found.In the correlation analysis of GLUCEST % value of each ROIs in CO poisoning group and subgroup with corresponding coma time,COHb concentration,MMSE score and HAMA score,the GLUCEST % values in thalamus and genu of the corpus callosum of CO poisoning group was negatively correlated with MMSE score(p <0.05),when there was no statistical difference in other groups.3.Graph theory analyse:The brain function networks of the CO poisoning group and the healthy control group have a higher clustering coefficient(γ> 1),but have almost the same characteristic paths as the random network Length(λ≈1),which indicates that the two groups have a typical small-world topology(σ> 1).However,the two-sample T-test showed significant differences in small-world attributes and network efficiency between groups(p <0.05).Compared with the control group,CO group has lower clustering coefficient Cp,normalized clustering coefficient γ and small world σ.The characteristic path length Lp and the normalized characteristic path length λ have no significant difference between the groups.In terms of network efficiency,CO group showed a significantly reduced local efficiency Eloc compared to the control group.There is no significant difference in global efficiency Eglob.In subgroup analysis,the small-world attributes and network efficiency of adults and children CO poisoning were consistent with those of the CO poisoning group.Compared with control group,the CO group showed lower nodal centrality and node efficiency in the right angular gyrus(AG.R),and higher nodal degree and nodal efficiency in the right Temporal Occipital Fusiform Cortex(TOF.R)and bilateral Occipital Fusiform Gyrus(OF).There are two significantly altered circuits in patients with acute monoxide poisoning.One neural circuit included 9 nodes and 8 edges(p < 0.05,FDR corrected),and all the edges showed decreased functional connection strength.The other neural circuit included 27 nodes and 38 edges(p < 0.05,FDR corrected),and all the edges showed increased functional connection strength..4.Dynamic functional Network connectivity:All d FNC states of all subjects were divided into one of the four states according to their similarity to the four cluster centers.State I(14% d FNC)was characterized by connections between SMN,CEN,and DMN networks with positive and negative couplings,and significant positive correlation within SMN and AUD networks.In State II,which accounts about 15% of all windows,SMN was positively correlated with VIS and CEN,while DMN was negatively correlated with AUD,VIS,and SMN.State 3(16% d FNC)is similar to State I,but the connectivity within and between networks is weaker than that in State I.In State IV,which accounts about 55% of all windows,FNC between all functional networks was very sparse.Compared to the control group,patients with acute CO poisoning had significantly increased mean dwell time and fractional windows in State II(p < 0.01).In the acute CO poisoning group,we found a positive association between the duration of coma and the mean dwell time of State II.In addition,the fraction window of State II was positively correlated with coma time.The subgroup analysis results revealed that State II of children patients had significantly higher fraction and mean dwell time than control group(p < 0.01).However,State IV of children patients had a significantly lower fraction and mean dwell time than HC group(p <0.01),and children patients with acute CO poisoning make more transitions than children control group.Conclusion:1 Changes in intracranial metabolites,including Cho,Glu,Gln and GABA,may occur in patients with acute CO poisoning at the early stage.Basal ganglia,especially globus pallidus,may be the most easily involved brain region after acute CO poisoning and could be used as the basis for the early diagnosis of acute CO poisoning.2 Glu CEST is more sensitive than MRS in detecting the changes of intracranial glutamate.The changes of GLUCEST% in thalamus and genu of the corpus callosum may be related to clinical conditions,and could be used as an auxiliary method for evaluation of brain injury after acute CO poisoning.3 Early brain functional network topological characteristics(small-world attributes and network efficiency),node indicators and brain functional network will changed after acute CO poisoning.The local efficiency and brain functional connectivity may be potential biomarkers for monitoring disease progression and severity of carbon monoxide poisoning.4 Acute CO poisoning has an impact on the state of functional connectivity network of the brain,and the duration of coma after CO poisoning has a greater impact on the state of functional connectivity.5 Acute CO poisoning has different effects on intracranial metabolites and brain functional network between adult and children.