Clinical Research Of Magnetic Resonance Multi-Modal Imaging Technology In Neonates With Hypoxic Ischemic Encephalopathy

Objective:By 3.0T MRI,collecting the data of T1 WI,T2WI,DTI and rs-fMRI of different degree of hypoxic ischemic encephalopathy,then analyzed the data: 1.to study the correlation about conventional MRI findings and clinical data and neurological prognosis of HIE neonates.2.To assess the neurodevelopment results on infants with HIE by using DTI technology including FA value,ADC value,voxel number and the diffusion tensor tractography(DTT)3.To compare the functional properties of resting state networks in different degrees of HIE,by useing functional MRI probabilistic tractography and graph theorySubjectsIt is a perspective study of children with 2013.01~2015.12 hospitalized at our Department.We select 46 term neonates with hypoxic ischemic encephalopathy having complete data: mild group(22 cases)and moderate group(24 cases).Diagnosis and inclusion criteria were in accordance with HIE diagnostic criteria and clinical classification of practical neonatal HIE,revised by Neonatology Group of the Chinese Pediatric Society of the Chinese Medical Association in Changsha,China in 2004.The disease was not stable at early stage,so MRI would be conducted at the ages of 8–14 days.There was no significant difference in gender,gestational age,mean weight or age on the day of examination among the three groups(P > 0.05),with comparability.All subjects were given 10% chloral hydrate 0.25–0.50 m L/kg by nasal feeding or enema,and subjected to scan after sleeping soundly.Methods:1.Using conventional magnetic resonance images(T1WI,T2WI)for analysis: scan parameters:Fov=180*180,Matrix=0.56*0.56*0.6mm,reconstruction=320,SENSES=2,slices=200 over contiguous=no,scan mode=3D,TFE factor=190,TR=shortest(11ms),TE= shortest(4.9ms),flip angle=8,NSA=1,Scan time=6min 34 s.Clinical data collection: To collect the clinical data by access to electronic medical records.Follow-up data collection: To do CDCC checkout in double blind test by two regular rehabilitation doctors.Tests were conducted in around age of one and MDI and PDI scores were record respectively.2.Using DTI method for analysis: Scans were performed on a 3.0 T MRI scanner with a head matrix coil.scan parameters:Fov=168*168,Matrix=1.5*1.5*2.0mm reconstruction=288,SENSE P=2,slices=50,slice gap=0,scan mode=MS,fast mode =EPI,TR=shortest(13114ms),TE=shortest(64ms),flip angle=30,Half scan=0.729,B=1000,direction resolution=33,NSA=2,Thickness= 2mm,Scan time=15min 45 s.The patient-specific image was segmented using the atlas' anatomical information.FA and ADC values in different areas of the specific patient images were calculated.b0,ADC,FA,and diffusion tensor tractography(DTT)diagrams were automatically generated with Neur03 D software.Twenty regions of interest(ROIs),including bilateral parietal cortex,deep white matter of the frontal lobe,anterior and posterior limbs of internal capsule,genu and splenium of corpus callosum,head of caudate nucleus,lenticular nucleus,thalamus,and pons,were selected in the b0 diagram.These ROIs were generated automatically,and were normalized with a neonatal model.Data were input into the software for automatic generation of ADC and FA values.3.Using DTI method for analysis:From January 2013 to December 2015,we recruited 22 full-term neonates with mild asphyxia(mild group)and 24 full-term neonates with severe asphyxia(severe group).Patient baseline data are listed in Table 1.Diagnosis and inclusion criteria were in accordance with HIE diagnostic criteria and clinical classification of practical neonatal HIE,revised by Neonatology Group of the Chinese Pediatric Society of the Chinese Medical Association in Changsha [12](The Subspecialty Group of Neonatology Pediatric Society Chinese Medical Association,2005).MRI exam would be conducted at the ages of 8–14 days because they are typically not sufficiently clinically stable to tolerate an MRI study at the first week after birth.Patients with any of the following entities would be excluded from the study: genetic metabolic diseases,central nervous system infection,congenital malformation of the brain,and chromosomal abnormality.There was no significant difference in gender,gestational age,mean weight or age on the day of examination among the two groups(P > 0.05),with comparability.Scans were performed on a 3.0 T MRI scanner(Philips Achieva,Philips Inc.,Rotterdam,the Netherlands).All Infants were given 10% chloral hydrate 0.25–0.50 m L/kg by nasal feeding or enema,and to scan after sleeping soundly.Heart and respiratory rates were continuously monitored by scanner automatically.A NICU staff member and one of families of the subject staid at the scanner room throughout the study.Images were collected using the following sequences: a turbo-spin echo T1-weighted sequence(T1W):TR9.3ms,TE4.4ms,FOV 180mm×180mm,Matrix 0.56×0.56×0.6mm3,Thickness 1.0mm,slices 200,slice gap 0,Scan time 6min 34s;a turbo-spin echo T2-weighted sequence(T2W): TR2651 ms,TE105ms,FOV180mm×180mm,Matrix1.5×1.5×1.6mm3,Thickness 4.5mm,slices 65,slice gap 0,Scan time 1min45s;rs-fMRI data were collected utilizing a gradient echo,echo-planar image(EPI)sequence: TR 1500 ms,TE(shortest)27ms,FOV 168*168,Matrix 2.4×2.4×3mm,reconstruction 256,slices 30,slice gap 0,flip angle 80,dyn scans 210,Scan time 5min 19 s.Total time 13 min 38s.Results1.The results of studying the correlation about conventional MRI findings and clinical data and neurological prognosis of HIE neonates:(1)There are significant differences in the incidence of abnormal both in PDI and MDI,the abnormal MRI rate and the abnormal rate of basal ganglia/thalamus(?~2=4.354,6.998 and 5.938,P<0.05).(2)According to the results of the MRI examination they are divided into basal ganglia/thalamus abnormal group(13 example)and other abnormal group(14).There were significant differences between the two groups compared with only MDI abnormal incidence and the incidence of abnormal both in PDI and MDI(?~2=3.935,6.694(P<0.05)There were also significant differences in 5 minutes Apgar score,umbilical cord blood PH value and the duration of convulsions(t= 2.012,3.132 and 2.225,P<0.05).(3)According to the CDCC score they are divided into sequela group(abnormal PDI and/or abnormal MDI 25 cases)and no sequela group(CDCC normal score 21 cases)and the clinical data of the two groups were statistically analyzed.There are significant differences in MRI abnormality rate and follow-up compliance(?~2=19.523,4.944,P<0.05),There are also significant differences in 5 minutes Apgar score,umbilical cord blood PH value and the duration of convulsions(t=2.135,3.004 and 3.124,P<0.05).2.The results of assessing the neurodevelopment results on infants with HIE by using DTI technology including FA value,ADC value,voxel number and DTT:(1)DTI parameters in normal,moderate HIE patients:(1)The ADC values in mild and moderate HIE patients have no significant difference(P > 0.05),FA values in the posterior limbs of the internal capsules and in the thalami showed statistically significant differences between the two HIE groups.(P < 0.05).(3)Voxel numbers in the superior longitudinal fasciculi,posterior limbs of the internal capsules and anterior limbs of the internal capsules showed statistically significant differences between the two HIE groups(P < 0.05).(2)DTT parameters in two group HIE patients:The tract numbers in the posterior limbs of the internal capsules,cingulate gyri,superior longitudinal fasciculi and inferior fronto-occipital fasciculi were significantly different between the two groups(P < 0.05).(3)Correlation between FA value and NBNA scores:All 10 cases of the control group had an NBNA score ? 35;the moderate HIE group included 3 cases scoring < 35,and 11 cases scoring ? 35;in the severe HIE group,all NBNA scores were < 35.F-test results showed that NBNA scores were significantly different among the three groups,with the severe HIE group having the lowest scores(P < 0.01).The correlation coefficient in the posterior limbs of the internal capsules was 0.646,higher than in other areas by Pearson relative analysis.The area under the ROC curve of FA values in the anterior limbs of the internal capsules was 0.779(P = 0.006),using NBNA scores ? 35 as a good outcome.FA values(? 0.395)in the posterior limbs of the internal capsules predicted a good outcome and the corresponding sensitivity and specificity was 70.2% and 79.5%,respectively.3.There was no significant difference in age,gender,gestational age and weight between the mild and moderate groups(p>0.05).One neurodevelopmental exam named Child Development Centre of China(CDCC)performed in all subjects at one-year old.CDCC contains intelligence development index(MDI)and the movement development index(PDI).Patients with severe HIE showed significantly higher rate of abnormal CDCC scores.Patients in moderate group with abnormal PDI score or MDI score are also more than in mild group.(1)Alterations in the global properties of functional networks in HIE patients.Both the two groups patients showed a small-world organization of functional networks characterized by ?>1 and ?? 1(Fig.1).However,compared with mild group,moderate HIE group exhibited decreased Eloc(p=0.0288)in the functional networks over a wide range of thresholds.Additionally,we also found low clustering coefficient(Cp)(P=0.0346)in moderate group(Table 2).There were no significant differences between the two groups in the other network metrics.(2)Alterations in the regional properties of functional networks.First,we identified the hub regions of the functional networks for each group.The nodes were considered brain hubs if their nodal efficiencies were at least 1 SD greater than the average nodal efficiency of the network.We found that the moderate group showed significantly fewer hub distributions(8 hubs)than mild groups(14 hubs).Further statistical analysis revealed that patients with moderate HIE had reduced nodal efficiency in the left rolandic operculum,left supramarginal gyrus,left and right temporal pole(superior temporal gyrus)and right temporal pole(middle temporal gyrus)Conclusion1.The degree of HIE is correlated with the prognosis of neurological development,but the children with mild HIE should not be ignored,especially those with abnormal neurological symptoms and MRI results.Conventional MRI has a certain value to predict the prognosis of neurological development in asphyxiated neonates,and if the injured sites are in basal ganglia/thalamus area,it is more likely lead to motor dysfunction.There are certain instruction value in prognosis referring to 5 mintes Apgar score,umbilical cord blood PH value and duration of convulsion.Furthermore,the early intervention in high-risk infants should be emphasized.2.FA values,voxel number,and number of fiber bundles in some ROIs quantitatively reflected white matter injury in neonates with HIE.The changes in DTI parameters were most obvious in the posterior limbs of the internal capsules,and may allow accurate and objective assessment of the degree of white matter injury in children with HIE.Among these parameters,the FA values in the posterior limbs of the internal capsules closely correlated with NBNA scores.DTI can be carried out in a single individual,so it has important clinical significance,and can accurately and objectively assess the prognosis.3.The present study shows disrupted topological organization of large-scale functional networks in moderate HIE patients.This may help us to further understand how disruptions of neuronal circuits underlie behavioral disturbances in moderate HIE patients.It may prodict the early brain development in children with moderate HIE and provides some guidance of early intervention in brain function.