弥散张量成像在早产儿脑白质损伤神经发育评价中的应用

脑白质损伤是早产儿最常见的脑损伤形式,是造成神经和智力损伤以及后期脑性瘫痪的主要原因.影像学检查在脑白质损伤的早期诊断及后期随访中发挥着重要的作用.其中核磁共振因为其安全准确的特点已成为目前应用最普遍的影像学检查.有别于传统的核磁共振技术,弥散张量成像可以在活体内观察和定量分析脑白质纤维束,现已成为评价脑白质损伤的有力工具.该文对弥散张量成像在早产儿脑白质损伤神经发育评价中的应用进行综述.     

早产儿感染与神经发育的远期预后

早产儿感染或炎症反应与神经发育的不良预后的关系日渐阐明,发育脑尤其是脑白质对细胞毒素和缺氧的易损性增加了认知和行为发育异常的风险.绒毛膜羊膜炎、脓毒血症和坏死性小肠结肠炎相关的感染或炎症与早产儿不良神经发育结果及生长密切相关,感染与脑损伤(包括脑室内出血和脑白质软化)也有联系,早产儿炎症介质介导的损伤造成了脑损伤和脑发育不良的结局.加强理解早产儿感染及炎症反应与脑损伤的关系有利于改善神经发育预后.     

早产儿感染与神经发育的远期预后

早产儿感染或炎症反应与神经发育的不良预后的关系日渐阐明,发育脑尤其是脑白质对细胞毒素和缺氧的易损性增加了认知和行为发育异常的风险.绒毛膜羊膜炎、脓毒血症和坏死性小肠结肠炎相关的感染或炎症与早产儿不良神经发育结果及生长密切相关,感染与脑损伤(包括脑室内出血和脑白质软化)也有联系,早产儿炎症介质介导的损伤造成了脑损伤和脑发育不良的结局.加强理解早产儿感染及炎症反应与脑损伤的关系有利于改善神经发育预后.     

应用弥散张量成像评价支气管肺发育不良早产儿脑白质发育的研究

目的 应用磁共振弥散张量成像（DTI）的各项异性分数（FA）和表观弥散系数（ADC）评价支气管肺发育不良（BPD）早产儿的脑白质发育。方法 以2016年8月至2019年4月生后24 h内收住NICU的出生胎龄≤32周、出生体重<1 500 g,且出院前完成头颅MRI及DTI检查的96例早产儿为研究对象。根据出院诊断分为BPD组（n=48）和非BPD组（n=48）,比较两组DTI相同感兴趣区的FA值和ADC值。结果 两组早产儿脑室周围-脑室内出血、脑室周围白质软化、局灶性脑白质损伤等发生率差异无统计学意义（P > 0.05）。BPD组早产儿内囊后肢、胼胝体压部、枕叶白质、小脑、大脑脚的FA值低于非BPD组（P < 0.05）,各ADC值高于非BPD组（P < 0.05）。与非BPD组相比,BPD组早产儿呼吸暂停次数更多、肺炎发生率和机械通气比例更高、辅助通气时间更长（P < 0.05）。结论 BPD对早产儿脑白质发育具有潜在影响,可导致脑白质发育延迟,因此,需关注该类患儿的神经功能。     

应用弥散张量成像评价支气管肺发育不良早产儿脑白质发育的研究

目的 应用磁共振弥散张量成像（DTI）的各项异性分数（FA）和表观弥散系数（ADC）评价支气管肺发育不良（BPD）早产儿的脑白质发育。方法 以2016年8月至2019年4月生后24 h内收住NICU的出生胎龄≤32周、出生体重<1 500 g，且出院前完成头颅MRI及DTI检查的96例早产儿为研究对象。根据出院诊断分为BPD组（n=48）和非BPD组（n=48），比较两组DTI相同感兴趣区的FA值和ADC值。结果 两组早产儿脑室周围-脑室内出血、脑室周围白质软化、局灶性脑白质损伤等发生率差异无统计学意义（P > 0.05）。BPD组早产儿内囊后肢、胼胝体压部、枕叶白质、小脑、大脑脚的FA值低于非BPD组（P < 0.05），各ADC值高于非BPD组（P < 0.05）。与非BPD组相比，BPD组早产儿呼吸暂停次数更多、肺炎发生率和机械通气比例更高、辅助通气时间更长（P < 0.05）。结论 BPD对早产儿脑白质发育具有潜在影响，可导致脑白质发育延迟，因此，需关注该类患儿的神经功能。     

围生期宫内感染与新生儿脑白质损伤

自从1962年Banker等命名脑室周围白质软化(periven-tricular leukomalacia,PVL)以来,新生儿脑白质损伤(white mat-ter damage,WMD)也越来越受到人们重视。WMD被认为是一组多相的、普遍的脑白质异常病变,多见于早产儿。Leviton等[1]认为WMD可被分为4种类型:1.脑白质出血性梗死;2.PVL;3.弥散性星形胶质化;4.弥散的凋亡现象。近年来随着我国围生医学及新生儿重症监护技术的飞速进展,早产儿的成活率越来越高,但脑性瘫痪(脑瘫)仍是成活早产儿的严重后遗症,给社会和家庭带来了巨大的负担。目前,WMD被认为是导致围生期死亡的重要病因,同时…     

问:早产儿头颅CT的脑白质密度值低于多少才有意义,如何诊断?仅依靠头颅CT能否诊断新生儿缺氧缺血性脑病?

答:不同胎龄新生儿的头颅CT存在与发育相关的低密度现象,早产儿(尤其是胎龄＜32周者)由于:(1)脑含水量高;(2)脑髓质化不完全;(3)缺乏髓鞘形成,因而脑白质低密度是一个正常发育过程,而非脑水肿及脑软化表现.因此,对早产儿不能轻易去评估脑白质低密度就是脑损害.目前存在的诊断误区是一些儿科和影像医师单凭早产儿脑白质低密度,不结合临床即轻易诊断重度缺氧缺血性脑病(HIE),这是不妥的.     

早期应用重组人促红细胞生成素对早产儿脑白质发育的影响

目的 应用磁共振弥散张量成像（DTI）的部分各项异性参数（FA）评价早期应用重组人促红细胞生成素（rhEPO）对早产儿脑白质发育的影响。方法 以81例胎龄≤ 32周、出生体重 < 1 500 g、生后24 h内住院的早产儿为研究对象,随机分为两组：rhEPO组（42例）使用rhEPO治疗,对照组（39例）使用等体积的生理盐水注射。2组均于纠正胎龄35~37周行头部MRI、DWI、DTI检查,并测定相同感兴趣区的部分各项异性参数（FA）。结果 两组早产儿颅内出血、脑室周围白质软化、局灶性脑白质损伤、广泛性脑白质损伤等发生率的差异无统计学意义（P > 0.05）。rhEPO组早产儿内囊后肢、胼胝体压部、额叶白质、枕叶白质FA值高于对照组（P < 0.05）,2组早产儿顶叶白质、丘脑、豆状核、尾状核FA值的差异无统计学意义（P > 0.05）。结论 早期应用重组人红细胞生成素对早产儿脑白质发育有神经保护作用。     

线粒体功能障碍与早产儿脑白质损伤的研究进展

早产儿脑白质损伤病因复杂,可导致长期的神经认知行为缺陷,目前尚无特效的治疗手段。越来越多的研究表明,线粒体功能障碍在早产儿脑白质损伤发病过程中起重要作用,可能是脑白质发育障碍的常见亚细胞机制,涉及氧化应激、ATP合成减少、钙稳态失衡。文章将对线粒体在脑神经发育过程中的作用和造成其功能障碍的机制作一综述,希望能够通过保护线粒体功能对早产儿脑白质损伤进行及早干预,为改善存活早产儿神经发育结局提供参考。     

NBNA评分联合磁共振弥散张量成像在早产儿脑白质发育评价中的作用及相关性分析

目的 探讨早产儿磁共振弥散张量成像中的各向异性分数（fractional anisotropy,FA）与新生儿行为神经测定（Neonatal Behavioral Neurological Assessment,NBNA）评分的相关性,从影像学角度评价FA在早产儿脑白质发育中的诊断价值。 方法 前瞻性选择2016年10月至2020年1月生后24 h内入住郑州大学第三附属医院新生儿重症监护室的98例早产儿为研究对象,根据NBNA结果分为异常组（<37分,51例）与正常组（≥37分,47例）,采集两组早产儿10个感兴趣区的FA值,比较两组间的差异,并分析FA值及脐动脉血气pH值与NBNA结果的相关性。 结果 异常组内囊后肢FA值、脐动脉血pH值低于正常组（P<0.05）。内囊后肢FA值、脐动脉血pH与NBNA评分呈正相关（分别r_s=0.584、0.604,P<0.001）;内囊后肢FA值与脐动脉血pH呈正相关（r_s=0.426,P<0.05）。 结论 早产儿内囊后肢的FA值能定量反映脑白质发育情况,其与NBNA评分具有相关性,二者结合能够更准确、更客观评价早产儿脑白质发育情况。 引用格式:     

Diffusion tensor imaging of brain development

Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.     

Connecting the developing preterm brain

White matter injury and abnormal maturation are thought to be major contributors to the neurodevelopmental disabilities observed in children and adolescents who were born preterm. Early detection of abnormal white matter maturation is important in the design of preventive, protective, and rehabilitative strategies for the management of the preterm infant. Diffusion Tensor Imaging (DTI) allows non-invasive, in vivo visualization and quantification of white matter tracts and has become a valuable tool in assessing white matter maturation in children born preterm. We will review the use of DTI to study white matter maturation and injury in the preterm brain.     

Appearances of diffuse excessive high signal intensity (DEHSI) on MR imaging following preterm birth

Background  

Diffuse damage to the periventricular white matter has recently been suggested to be a cause of the cognitive deficits seen following preterm birth. It is unclear whether this form of injury can be visualised on MR imaging, but one group has described diffuse excessive high signal intensity (DEHSI) as a possible form of diffuse white matter injury. This finding is dependant on window imaging and the subjective assessment of the reviewer, but little data have been published on the degree of subjectivity on its appearance among raters.     

Diffuse axonal injury in periventricular leukomalacia as determined by apoptotic marker fractin

Periventricular leukomalacia (PVL), the major substrate of neurologic deficits in premature infants, is associated with reduced white matter volume. Using immunomarkers of axonal pathology [beta-amyloid precursor protein (beta-APP) and apoptotic marker fractin], we tested the hypothesis that widespread (diffuse) axonal injury occurs in the gliotic white matter beyond the foci of necrosis in PVL, thus contributing to the white matter volume reduction. In a cohort of 17 control cases and 13 PVL cases with lesions of different chronological ages, diffuse axonal damage in PVL was detected by fractin in white matter sites surrounding and distant from acute and organizing foci of necrosis. Using beta-APP, axonal spheroids were detected within necrotic foci in the acute and organizing (subacute) stages, a finding consistent with others. Interestingly, GAP-43 expression was also detected in spheroids in the necrotic foci, suggesting attempts at axonal regeneration. Thirty-one percent of the PVL cases had thalamic damage and 15% neuronal injury in the cerebral cortex overlying PVL. We conclude that diffuse axonal injury, as determined by apoptotic marker fractin, occurs in PVL and that its cause likely includes primary ischemia and trophic degeneration secondary to corticothalamic neuronal damage.     

Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques

Periventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and less prominent, more diffuse cerebral white matter injury. The early detection of the latter, diffuse component of PVL is not consistently possible with conventional brain imaging techniques. We demonstrate the early detection of the diffuse component of PVL by diffusion-weighted magnetic resonance imaging (DWI). In a premature infant with no definite cerebral abnormality detectable by cranial ultrasonography or conventional magnetic resonance imaging, DWI showed a striking bilateral decrease in water diffusion in cerebral white matter. The DWI abnormality (ie, decreased apparent diffusion coefficient) was similar to that observed with acute cerebral ischemic lesions in adults. At 10 weeks of age, conventional magnetic resonance imaging and ultrasonography showed striking changes consistent with PVL, including the presence of small cysts. The observations indicate the importance of DWI in the early identification of the diffuse component of PVL and also perhaps the role of ischemia in the pathogenesis of the lesion.     

Periventricular leukomalacia: overview and recent findings.

Periventricular leukomalacia (PVL), the main substrate for cerebral palsy, is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The classic neuropathology of PVL has given rise to several hypotheses about the pathogenesis, largely relating to hypoxia-ischemia and reperfusion in the sick premature infant. These include free radical injury, cytokine toxicity (especially given the epidemiologic association of PVL with maternofetal infection), and excitotoxicity. Among the recent findings directly in human postmortem tissue is that immunocytochemical markers of lipid peroxidation (hydroxy-nonenal and malondialdehyde) and protein nitration (nitrotyrosine) are significantly increased in PVL. Premyelinating oligodendrocytes, which predominate in periventricular regions during the window of vulnerability to PVL (24 to 34 postconceptional weeks), are the targets of this free radical injury, and suffer cell death. Susceptibility can be attributed, at least in part, to a relative deficiency of superoxide dismutases in the preterm white matter, including premyelinating oligodendrocytes. Several cytokines, including interferon-gamma (known to be directly toxic to immature oligodendroglia in vitro), as well as tumor necrosis factor-alpha and interleukins 2 and 6, have been demonstrated in PVL. Microglia, which express toll-like receptors to bacterial products such as lipopolysaccharide, are increased in PVL white matter and may contribute to the injury. Preliminary work suggests a role for glutamate receptors and glutamate transporters in PVL, as has been seen in experimental animals. These findings pave the way for eventual therapeutic or preventive strategies for PVL.     

Cortical Dysgenesis in a Variant of Phenylketonuria (Dihydropteridine Reductase Deficiency)

The neuropathology of a 2 1/2-year-old patient with dihydropteridine reductase deficiency showed diffuse demyelination throughout white matter and spongy vacuolation in the long tracts of the brain stem. These changes are characteristic neuropathologic observations in untreated phenylketonuria. In addition, extensive neuronal loss, calcification and abnormal vascular proliferation were noted in the cerebral cortex, white matter, basal ganglia, and thalamus. Golgi studies demonstrated an abnormal orientation of neurons together with abnormalities of dendrites and dendritic spines. The pathogenesis of the vascular abnormalities in this condition is unknown, although folate deficiency may be involved. The secondary deficiency of serotonin and dopamine occurring during neuronal growth and differentiation may also affect the terminal stages of neuronal maturation.     

脑白质损伤防治新标靶——神经血管单元

围生期脑白质损伤是导致早产儿神经系统发育受损甚至远期后遗症最常见的脑损伤形式.其发病机制复杂,目前尚缺乏有效的防治手段.近年来,神经血管单元作为神经系统结构和功能的整体,逐渐在神经科学领域引起关注.该文就脑白质中神经血管单元的组分及相互作用,脑白质损伤的病理生理、预防和治疗等方面的研究进展作一综述.