Study Of Brain Multi-modal Magnetic Resonance Imaging Of Hyperbilirubinemia Of Neonates

Background and purpose:In the past,clinical diagnosis of bilirubin encephalopathy mainly rely on laboratory tests and clinical manifestations.It is generally believed that the bilateral,symmetrical increased T1 WI signal in the globus pallidus and subthalamic nucleus on magnetic resonance imaging(MRI),in the first day to several weeks after the onset of acute bilirubin encephalopathy in newborns.Because of the presence of myelin in these structures,frequently showing increased T1-signal in these regions,it may give false-positive findings in newborn infants.It is well known that the conventional magnetic resonance imaging of bilirubin encephalopathy is mainly dependent on the experience of a magnetic resonance imaging doctor.Subjectivity,lack of objective quantitative or semi quantitative analysis,which inevitably lead to some bias.Moreover,different types of machines and different sequences will have an impact on the diagnosis of acute bilirubin encephalopathy.Therefore,we only study the MRI manifestation of the neonatal hyperbilirubinemia,due to premature infant brain development is not mature,and it has large differences in different ages of preterm infants.The objective of this study was to establish an objective diagnostic criteria for magnetic resonance imaging,and to understand the relationship between T1 high signal and total serum bilirubin and the relation of neonatal assessment of behavioral and neurological(NBNA)scores.The advanced imaging techniques of MRI continue to offer promise both as a means of establishing an early biomarker of injury and as a tool to better understand the pathogenesis of bilirubin-induced neurologic damage and the adverseneurodevelopmental outcome of infants with Chronic bilirubin encephalopathy(CBE).With the development of MRI technology,advanced magnetic resonance imaging such as diffusion weighted imaging(DWI),diffusion tensor imaging(DTI),Diffusion Tensor Tractography(DTT),Susceptibility Weighted Imaging(SWI)were developed on the basis of conventional magnetic resonance imaging(MRI)。These may provide new insights into the pathogenesis of bilirubin induced brain injury,and provide the basis for the diagnosis of long-term disability in children with chronic bilirubin encephalopathy.At present,in the study of hyperbilirubinemia,there are more research works had been done on magnetic resonance spectroscopy(MRS),but the results were different;and little researchs on diffusion tensor imaging(DTI);almost no research on Magnetic susceptibility weighted imaging(SWI).Thus,much work remains to be done regarding advanced imaging techniques on MRI in neonates with bilirubin encephalopathy in regards to diagnosis,prognosis,and furthering our understanding about the pathogenesis of bilirubin neurotoxicity.So,we studied the multi-modal MRI which including diffusion weighted imaging,diffusion tensor imaging,magnetic resonance spectroscopy,magnetic susceptibility weighted imaging in neonatal hyperbilirubinemia,in order to further understand the brain metabolites of term newborns with hyperbilirubinemia,the changes of water diffusion movement in brain,and wheather have bleeding injury changes,in order to further understanding the pathophysiology of the bilirubin toxicity caused by cell injury or death.In addition to diffusivity and cytotoxic edema,diffusion tensor imaging(DTI)with tractography may be useful for elucidating long-term changes along specific anatomical pathways.The subcortical regions most affected in CBE globus pallidus,subthalamic nucleus,substantia nigra,dentate nucleus(cerebellum),and hippocampus—are interconnected with each other as well as other cortical and subcortical brain regions via numerous white matter pathways(e.g.,cortico-ponto-cerebello-thalamo-cortical pathway and cortico-striato-thalamo-cortical pathways),and it is not known how these pathways are affected in the long-term in infants or children with CBE.DTI and tractography could be used to delineate long-term changes involving specific white matter pathways,further elucidating theneural basis of long-term disability in infants and children with CBE.Therefore,We shall study DTI of full-term neonates with severe hyperbilirubinemia whose serum bilirubin level is more than 20mg/dl,and measure the value of DCav,FA,ISO in motor cortex,subcortical regions,globus pallidus,thalamus,substantia nigra,pontine nuclei and dentate nucleus.The values will be statistical analysised to confirm wheather there have differences between the acute bilirubin encephalopathy group and normal control group,so as to provide evidence for the presence of specific neural pathways in the neonatal bilirubin encephalopathy.In view of this,the study is divided into three parts to carry on the research of neonatal hyperbilirubinemia.In the first part,we will study MRI and MRS appearances of full-term neonatal hyperbilirubinemia and contrast analysis with clinical.The second part,we will study Diffusion tensor imaging and Magnetic susceptibility imaging of basal ganglia in full-term neonatal hyperbilirubinemia.The third part,we will study the effect on dentate nucleus-thalamus-cortex pathways with full-term neonatal acute bilirubin encephalopathy on MR Diffusion Tensor Imaging.Part 1 Study of brain MRI and MRS on full-term neonates with hyperbilirubinemia and contrast analysis with clinicalObjective : To investigate the MRI and ~1H-MRS findings of Neonatal Hyperbilirubinemia,and the correlation between MRI findings and total serum bilirubin level and NBNA score of neonates.Methods:According to serum bilirubin level(serum total bilirubin level ≥205μmol/L)a total of 73 mature newborns with hyperbilirubinemia(study group)were divided into 3 groups,which included mild elevation group,moderate elevation group,severe elevation group.Other 29 healthy full-term neonates(serum total bilirubin level <205μmol/L)were collected as normal control group.Cerebral MRI was performed in all neonates.Additional ~1H-MRS examination was employed in 13 neonates of the study group as well as in 10 healthy neonates of the control group.To study the relationship of MRI findings with total bilirubin level and the average signal values of globus pallidus for MRI T1 WI,and to evaluate MR spectroscopy in diagnosing neonatal hyperbilirubinemia.In the case of hyperbilirubinemia will follow MRI T1 WI Signal increased with the signal normal divided into 2 groups,to measure the NBNA score of 2 groups,to compare of two groups of neonates with hyperbilirubinemia NBNA score if there was statistical significance.Results:1 The increased MRI T1 WI signal of globus pallidus in the neonates of the study group,T2 WI and DWI no abnormal signal.2 For moderate to severe elevated group(serum total bilirubin level ≥ 342μmol/L),there was statistical significance compared with normal control group.The globus pallidus average signal values is 1088 ± 239.65,median value is 1008,unilateral 5% confidence interval the lower limit value is 799.3 There was no significant difference between the normal control group and thelesion group on the difference between the bilateral globus pallidus and frontal white matter signal values.4 Globus pallidus average signal value is linear positive correlation with the different levels of bilirubin.5 Compared with the normal control group,~1H-MRS examination indicated that in the study group the ratios of NAA/Cr,Cho/Cr and Cho/NAA were not statistically significant.But the ratios of m I/Cr and Glx/Cr were increased,and they were statistically significant.6 Lesion group were divided into 2 groups,including 27 cases of visual observation of globus pallidus increased T1 WI signal,measuring the average signal value above 799,as the higher group,NBNA score was 34.62±3.15 36 cases of globus pallidus were normal and the average signal value was less than 799,which was set as the normal group.The NBNA score was 37.03±0.77.The P value of the two groups was statistically significant difference between the two groups.Conclusion:On MRI T1 WI the signal of globus pallidus was increased with the increase of serum bilirubin level,and they were with relevant relations.Especially when serum total bilirubin level≥342μmol/L,the average signal value of the globus pallidus was more than 799,indicating that signal was increased.And the globus pallidus increased signal,can be used as one of the clinical diagnosis and it indicted that brain damage may be present.The difference of globus pallidus and ipsilateral frontal white matter signal measured by MRI T1 WI is not as sensitive as that of globus pallidus.The ratio of m I/Cr and Glx/Cr on ~1H-MRS were increased in neunatal hyperbilirubinemia,and increasing of the metabolites of m I and Glx suggested that cell injury may be exist.Part 2 Study of Diffusion tensor imaging and Magnetic susceptibility imaging of basal ganglia in full-term neonates with hyperbilirubinemiaObjective : To investigate the conventional magnetic resonance imaging,diffusion tensor imaging and magnetic susceptibility imaging in diagnosis of neonatal hyperbilirubinemia.Methods:According to serum total bilirubin level 15 cases of full-term newborns with mild elevated group,10 cases of moderate to severe elevated group,and 10 cases of the normal control group,were performed conventional MRI and DTI,SWI in all neonates.On three groups of globus pallidusand posterior limb of internal capsule FA and DCav value for statistical analysis.The lesions were divided into the signal rise group and the normal group according to the magnetic resonance signal,and the two group of globus pallidus,posterior limb of the internal capsule FA and DCav value for statistical analysis.To observe whether SWI had abnormal hemorrhage.Results:1 There was no statistical significance the FAand DCav values of the bilateral globus pallidus in the lesion groupcompared with the normal control group,there was statistical significance FA and DCav values of the bilateral posterior limb of internal capsule compared with the normal control group,the P values were 0.014 and 0.047.2 There was no statistical significance between globus signal rise group and the normal groupof globus pallidus,posterior limb of the internal capsule FA and DCav value.3 In 3 cases of conventional MRI,the punctate lesions were found in the posterior horn of lateral ventricle.No abnormal high signal was found in all cases on DWI.4 In all cases,there was no hemorrhage in SWI.Conclusion:SWI showed that brain injury had no bleeding foci in neonatal hyperbilirubinemia.When the serum total bilirubin level ≥342 mol/L,the posterior limb of the internal capsule DCav decreased,FA increased,suggesting that cell edema,the disease may recover,can prompt clinical treatment as soon as possible,to reduce the occurrence of sequelae.Part 3 Study value about brain nerve conduction pathway of full-term neonatal acute bilirubin encephalopathy on Diffusion Tensor ImagingObjective: The serum bilirubin level is more than 20mg/dl,which is clinically diagnosed with acute bilirubin encephalopathy.We collected full-term newborns of increased T1 weighting imaging(T1WI)signal on conventional magnetic resonance imaging(MRI),and then performed quantitative analysis research applying diffusion tensor imaging(DTI).This study intended to explore the influence of hyperbilirubinemia(HB)on dentate nucleus-thalamus-cortex pathways,further provide more evidence for existence of specific neural pathways in bilirubin toxicity effects of newborn acute bilirubin encephalopathy.Methods: We collected 30 full-term newborns of blood bilirubin more than20mg/dl as the experimental group and 10 normal full-term newborns as the control group.All participants were performed applying with conventional MRI and DTI.The DTI data of two groups newborns were processed by ADW4.4 functool software.Then we respectively measured DCav、FA and ISO values in ROIS of bilateral frontal lobe precentral gyrus cortex、frontal white matter、lateral ventricle body besides white matter、globus pallidus、posterior limb of internal capsule、thalamus、hippocampus、locus ruber、pons nuclei、medulla oblongata and dentate nucleus.By comparing the above values between the experimental group and control group,we observed that whether there is statistical significance between the two group.Results:1 Compared with the control group,the DCav and ISO values in the bilateral frontal lobe precentral gyrus cortex 、 posterior limb of internal capsule 、 dentate nucleus were decreased;on the contrary,the FA in the above brain areas was enhanced.The differences were respectively statistically significant and P<0.05.2 Compared with the normal control group,the ISO value in the bilateralsplenium of corpus callosum、globus pallidus、locus ruber、hippocampus、pons nuclei was decreased,with statistical significance(P<0.05).However,the DCav and FA values in the above brain areas have no statistical significance(P>0.05).3 The DCav、ISO and FA values in the bilateral frontal white matter、lateral ventricle body besides white matter、thalamus、hypothalamus、medulla oblongata between the two groups has no statistical significance(P>0.05).Conclusion: Our results in this study suggest that there exists transduction pathway of motor cortex-posterior limb of internal capsule-hippocampus-locus ruber-pons nuclei-cerebellar dentate nucleus.The pathway is mostly consistent with the cortex-pons-cerebellum-thalamus-cortex pathway,which was suggested by Wisnowski.The transduction pathway among cerebrum、thalamus、hippocampus、pons、cerebellar dentate nucleus and cortex reveals that bilirubin neurotoxicity may extend the specific neural pathway in the acute bilirubin encephalopathy.Therefore,the abnormal ADC 、 FA and ISO values in acute bilirubin encephalopathy demonstrates the cortico-ponto-cerebello-thalamo-cortical pathway mode and expand easily infringed brain areas by bilirubin toxicity to specific neuroanatomy pathways.Furthermore,this DTI study provides reliable evidences for the pathophysiological mechanisms of the bilirubin encephalopathy with noninvasive methods.