Applied Value Of FA Value In Full-term Neonatal Hypoxic-ischemic Encephalopathy With Magntic Resonance Diffusion Tensor Imaging

1、Background and Objection1.1 BackgroundHypoxic-ischemic encephalopathy(HIE) refers to partly or completely asphyxia, cerebral blood flow reduction or interruption which leads to fetal or neonatal brain damage resulted from the various kinds of perinatal asphyxia, is one of the important reasons for neonatal acute death or chronic neurological damage. Kurinczuk reported that HIE occured in 1.3-1.7per 1000 live birth in developed country, the developing country was higher.Mild cases can be healed, the severe cases can lead to children with low intelligence, retardation, cerebral palsy, epilepsy, and even death. The long term life quality of children is seriously affected, which brings heavy burden to family and society. Before two-year-old, the brain of children is flexible and in the high-speed development state, if positive clinical interventions conducted during this period can reduce the incidence of neurological sequelae and disability. Therefore, early diagnosis of HIE and accurately determine the scope and extent of damage in children is very important, At the same time, an accurate assessment of the influence which HIE impacts on white matter development also attracted wide attention.At present, clinical diagnosis of HIE is primarily based on whether children with asphyxia and neurological symptoms after birth. The clinicians often use Apgar scores to determine whether neonatal with asphyxia,but most scholars raise doubts, because Apgar scores will be affected by a number of factors outside of asphyxia, such as:gestational age, neonatal maturity, drugs and other factors, as compared to the normal full-term neonatals, normal premature newborns have lower muscular tension,weaker primitive reflexes, and the analgesia also has influence on Apgar scores121. Considered a low Apgar score is not equivalent to asphyxia. The conventional Apgar score had the low sensitivity(81%) and low specificity (81%). The scholar reviewed 88 cases of HIE and found that the Apgar score of 30 cases of HIE caused by intrauterine asphyxia was normal,not reduce.A group of foreign research data showed that the Apgar scores of about 21 percent HIE neonatals did not significantly reduce. Therefore, Apgar score did not completely reflect the extent and severity of asphyxia.On the other hand, there is a therapeutic time window in the process of HIE brain injury, the time window in human neonatals are 6 hours. And at this time,the neurological symptoms of HIE neonatals may not occur, therefore, it is subjective and lagging that diagnose HIE based on clinical manifestations.Neonatal hypoxic-ischemic encephalopathy is a serious complication of asphyxia, different severity, the prognosis is quite different.Studies have shown that within 3 years old, the incidence of poor prognosis in neonatal with moderate HIE was 32 percent, almost 100 percent in severe HIE, dose not occur in neonatal with mild HIE. Study had also pointed out, children with mild HIE will have better prognosis, severe HIE may occur high mortality and severe neurological malformations, while larger differences prognosis in children with moderate HIE,vary normal nervous system development to severe cerebral palsy,developmental delay and epilepsy. However, there also reported that mild HIE may occur motor function disorders. The current prognosis method mainly based on clinical manifestations, laboratory tests and imaging findings, there is no uniform quantitative criteria. For HIE, whether the disease affected the development of white matter and myelination is an important basis to determine whether there is movement and mental retardation and other adverse sequelae. How to take advantage of imaging methods early found the brain damage caused by HIE and assess white matter myelination in children has been a hot neonatal imaging study,and also has important clinical implications.With the rapid development of medical imaging technology, and its increasing applications in the neonatal brain disease, the ultrasound has many advantages, such as:easy, non-invasive, lower inspection costs and can be more clearly show the structure of the ventricular morphology and its surroundings. Color Doppler ultrasound can provide cerebral blood flow indicators to assess clinical efficacy, However, due to the influence of newborn’s skull, ultrasound is much inferior than CT and MR in showing lesions in the edge of brain and intracranial brain hemorrhage.CT examination is fast, simple, has a unique advantage to show the location and extent of intracranial hemorrhage, But in the early process of HIE may only showed cerebral edema, low-density areas in the brain parenchyma, due to neonatal brain have high water content, density is lower than normal adults, the low-density caused by brain edema lack contrast with normal low-density surrounding white matter, therefore,CT may lead to misdiagnosis and has certain limitations in the early diagnosis of HIE. In addition, due to radiation damage, CT has more limited its application in terms of neonatal brain.MRI with its advantages of multi-perspective, multi-parameter, no radiation occupies an important position in the diagnosis of neonatal brain disease, it can clearly show brain damage caused by HIE and the type of injury, HIE early brain injury can be divided into three types: ① focal cortical damage, including the damage of watershed area; ② basal ganglia, thalamus and cortex centers injury;③ diffuse brain injury; late mainly shown focal or multifocal cerebral softening, delayed myelination, external hydrocephalus, brain atrophy and poor development of the corpus callosum. However, conventional MRI with a certain lag in early show HIE brain damage, in the first few hours or a few days of HIE brain injury, the conventional MRI has often no positive findings.With the disappearance of cerebral edema, conventional MRI which conducted 2-4 weeks after birth can predict neonatal outcome. The study shows that the predominant pattern of injury, which is established on conventional MRI by the second week of life, is more strongly associated with neurodevelopmental outcome than the severity of injury in any one region However, prognosis HIE based on conventional MRI is limited in the initial days of life until the predominant pattern of injury is fully apparent and does not provide a quantitative standard.DWI (diffusion weighted imaging) detect the water molecules diffusion motion to react the change the microstructure, but the change of the image signal on DWI were not only representative the diffusion motion of water molecules, but also affected by other factors, such as:arterial pulse, respiration and blood flow and this factors will cause a change in the signal, so the signal in the image detected by DWI through the change of the organization’s signal is not a real change in the diffusion coefficient,is the apparent diffusion coefficient (ADC), through the changes of ADC values can quantitatively assess the speed of water diffusion, movement. Many studys show that DWI play an important role in the early diagnosis of HIE, it can have positive findings within 24 hours after hypoxic-ischemic injury. But there are "paeudonormalization" phenomenon, namely after hypoxic-ischemic injury, ADC value early reduce then rising back to normal levels. During this period, ADC values do not reflect brain damage. At the same time,there are defects of DWI, such-as: false negative and underestimate the extent of damage. Visible, DWI has certain limitations in the early diagnosis of HIE.MR diffusion tensor imaging (DTI) is a new imaging technology which can in vivo display white matter fiber bundle orientation and integrity that developed on the basis of DWI. DWI can only reflect diffusing on the direction of diffusion gradient field, DTI apply more than 6 diffusion gradient field direction, can be more accurately reflected the water molecules diffuse situation in the space. The water molecules have same movement in all directions in the free water, this phenomenon called isotropic. Due to the cell membrane and myelin coating, water molecules diffuse much faster in the certain directions than in other directions which called anisotropy. Through its characteristic parameters, DTI can reflect the anisotropic of water molecules diffusion. Most studies show that, DTI is more sensitive than conventional MRI in the early diagnosis of HIE, and also can quantitatively assess the condition of HIE newborns. Studies have shown that^15’, ischemia and hypoxia occurred within 24h, FA values decrease in white matter fiber tracts. Animal experiments also show that, DTI may confirm the diagnosis of acute and hyperacute hypoxic-ischemic brain damage.Takeda et al researchers found that in the process of white matter fiber tracts myelination, the diffusion anisotropy changes earliest, indicating that the DTI can provide important basis for early detecting the brain injury of HIE. DTI can assess the white matter development status and evaluate the prognosis of HIE children. Nora Tusor and other scholars using the technology of Tract-based spatial statistics (TBSS) calculated DTI characteristic parameter (FA values), showed that FA values and developmental quotient were positively correlated. It shown that FA values of white matter fiber were related to early prognosis of HIE neonatals. Measure the FA values can early predict the prognosis of HIE neonatals. Meanwhile, in the follow-up review stage, FA values can objectively response the effect of hypoxic-ischemic events in HIE white matter myelination and assess the white matter development status.1.2 research purposesThis study was a retrospective analysis which analyze imaging and neurological score in nearly four years of full-term neonates with HIE in Southern medical university affiliated Shenzhen Maternity Maternity& Child Healthcare Hospital. We did this study to explore the applied value of DTI important parameter (FA value) in early diagnosis of full-term neonates with HIE; In early prognosis assessment, seek an cut-off point FA values to provide a quantitative index for clinicians assessing prognosis early. To explore the application of FA values in the followed up of term neonates with HIE.2. Materials and Methods2.1 research objectCollected 50 cases from April 2010 to December 2014 who were born in our hospital and conducted MRI magnetic resonance scanning routine sequence and DTI sequences. After HIE children six months old, conducted Bayley Scales of Infant Development (BSID) score in our hospital Child Health Division. gestational age 37-42 weeks; HIE diagnostic criteria refers to "neonatal hypoxic-ischemic encephalopathy diagnostic criteria " formulated by Chinese Medical Sciences branch of neonatology group in 2005. At the same time set up 25 cases of normal newborns as the control group, the control group inclusion criteria, gestational age 37-42W; no significant perinatal asphyxia and fetal distress performance; 1 and 5min Apgar score were= 8 points; umbilical arterial PH= 7.00; cranial MRI showed no abnormalities; no central nervous system infection and congenital malformations; no significant metabolic disorders and chromosomal disorders; no neurological symptoms and signs; neurobehavioral assessments meet the appropriate age children behave. In the late stages of track review, collected 23 full-term neonates with HIE who were reconducted cranial MRI of aforementioned 50 HIE neonates. the review time control in 3-6 months, according to the age distribution of case group,set up 23 normal infants as controls. Group inclusion criteria: ① full-term newborns;② no central nervous system disease, no history of seizures, perinatal asphyxia, congenital malformations and heritage metabolic diseases, mother has no history of drug abuse during pregnancy. ③ age distribution as same as the children in the experimental group.2.2 experimental methodsThe first time DTI examination:A total of 50 term newborns were diagnosised with HIE. According to the clinical diagnosis, all cases were divided into mild, moderate and severe groups, while 25 newborns who have normal central nervous system were selected as a control group. All of the subjects were conducted conventional magnetic resonance scanning sequence and DTI sequence, selected the frontal white matter, internal capsule limb, lenticular nucleus, corpus callosum, cerebral peduncle and semi-oval center as ROIs (region of interest ROI), FA values were calculated in every regions of interest and compared between groups. All patients underwent BSID assess the prognosis after six months, according to the prognosis the cases were divided into good prognosis and poor prognosis groups. Compared the FA values which was obtained within one week in each region of interest between the good prognosis and poor prognosis.ROC curve were applied to analysis the diagnostic performance of each region of interest, got the FA value cut-off point, the sensitivity and specificity.Review DTI:23 cases of HIE who were carried out review DTI in our hospital were divided into two groups, review mild HIE group and moderate-severe group, and set 23 Central Nervous System normal infants as controls, all subjects underwent conventional magnetic resonance and DTI sequence scanning, measured FA value of each region of interest. Compared the FA values between groups.3. Results3.1 FA values in frontal white matter、posterior limb of internal capsule^ splenium of copus callosum、cerebral peduncle centrum semiovale were different and the difference was statistically significant (P<0.05); FA values in lenticular nucleus between the two groups showed no significant difference (P> 0.05); In Pairwise comparisons, FA values in part ROIs were different and the difference was statistically significant (P<0.05); In comparisons between brain parenchyma was no abnormal results in conventional MR of HIE group and control group, the FA value in frontal white matter、posterior limb of internal capsule and splenium of copus callosum were different and the difference was statistically significant (P<0.05).3.2 In addition to the lenticular nucleus, FA value in each region of interest between relatively good prognosis and poor prognosis group during the first DTI scan were different and the difference was statistically significant (P<0.05); In addition to the lenticular nucleus, each region of interest has the strong ability of assessing the prognosis, when taken the cut-off point FA value of posterior limb of internal capsule≥0.432, the sensitivity was 94.7%, specificity was 84.6%, area under the curve was 0.943, Youden index was 79.3%;3.3 In the review stage of HIE, except lenticular nucleus, FA values in each region of interest of the review moderate-severe group were reduced compared with the control group and the review mild group, and the difference was statistically significant (P<0.05); FA values in internal capsule limb and splenium of copus callosum of review mild group were reduced compared with the control group, and the difference was statistically significant (P<0.05)4. Conclusion4.1 Compared with conventional MRI, DTI may early, objectively evaluate the extent of brain damage in neonatals with HIE, FA values can provide a basis for early diagnosis of HIE, assess the severity and provide guidance for clinical treatment.4.2 FA values can early assess the prognosis of HIE, the prognosis of efficiency of the internal capsule limb was higher, can be used as a reference index for the clinical assessment of prognosis.DTI technique has important prognostic value in newboras with HIE.4.3 The characteristic parameter of DTI (FA values) can objectively response the influence that hypoxic-ischemic injury impacted on the development of white matter fiber tracts, assess the situation and development of white matter in neonatals with HIE during the review stage.