多体素磁共振波谱成像在早产儿脑发育研究中的价值探讨
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摘要
目的通过多体素氢质子磁共振波谱成像(~1H-MRS)探讨围产期高危因素对早产儿脑组织代谢的影响及代谢产物对神经系统发育落后的预测价值。方法对60例早产儿在36周<矫正胎龄≤37周行头颅MRI及~1H-MRS检查,并于出生后40周行Gesell发育量表检测,最终46例早产儿被纳入研究并分为四组:围产期正常组12例、缺氧窘迫组10例、感染组12例、缺氧窘迫伴感染组12例,分别测定基底节及丘脑(BGT)、两侧脑室周围白质(WM)的N-乙酰天门冬氨酸(NAA)/肌酸复合物(Cr)、胆碱复合物(Cho)/Cr、乳酸(Lac)/Cr比值,四组组间数据行单因素方差分析;对NAA/Cr、Cho/Cr、Lac/Cr及发育商(DQ)分别作Spearman相关分析,当P<0.05,对各参数与DQ作线性回归分析;利用受试者工作特征(ROC)曲线计算各代谢产物对神经系统发育落后的预测能力。结果围产期正常组分别与缺氧窘迫组、缺氧窘迫伴感染组比较,感染组与缺氧窘迫伴感染组比较,在BGT及WM区域,NAA/Cr、Cho/Cr、Lac/Cr差异均有统计学意义(P<0.01);围产期正常组与感染组比较,缺氧窘迫组与缺氧窘迫伴感染组比较,仅在WM区域,Cho/Cr差异有统计学意义(P<0.05);各代谢物之间及与DQ之间有强相关性,BGT区域NAA/Cr、Cho/Cr与DQ的回归方程决定系数较高(0.6742、0.5649),并且对神经系统发育落后预测能力最强,曲线下面积(AUC)分别为0.940、0.955。结论围产期缺氧直接影响髓鞘化进程及神经元的完整性;围产期感染仅对脑白质区神经纤维髓鞘化进程有影响;BGT区NAA/Cr、Cho/Cr比值的联合应用可以较准确预测早产儿神经系统发育落后。
Objective To investigate the influence of perinatal risk factors for metabolite levels in brain of preterm neonates by using multi-voxel magnetic resonance spectroscopy and its predictive value for nervous system developmental delay. Methods A total of 60 preterm neonates at term-equivalent age underwent MRI examination,the MRI examinations including multi-voxel ~1H-MRS and other conventional plain sequences were performed using MAGNETOM Skyra(Siemens Healthcare,Erlangen,Germany),and the Gesell examination was performed at 40 weeks after birth. 46 preterm infants were finally enrolled in this study and were divided into four groups:Group1( n = 12,perinatal normal),Group2( n = 10,perinatal asphyxia),Group3( n = 12,perinatal infection) and Group4( n = 12,perinatal asphyxia and infection). NAA/Cr、Cho/Cr、Lac/Cr ratios were collected from voxels located in the basal ganglia and thalami( BGT) and periventricular white matter( WM). Metabolic values were analyzed by one-way ANOVA across four groups,the correlations between each metabolite and development quotient( DQ) were analyzed by linear regression analysis and evaluate the predictive value for nervous system developmental delay by using receiver operating characteristic curve( ROC). Results Both in BGT and WM regions,the differences of all metabolic values including NAA/Cr,Cho/Cr and Lac/Cr ratios were statistically significant between Group1 and Group2,between Group1 and Group4,between Group3 and Group4. Only in WM region,the difference of Cho/Cr ratio was statistically significant between Group1 and Group3,between Group2 and Group4. The analysis of spearman's correlation demonstrated that DQ had significant correlations with each metabolite in BGT and WM,the determination coefficient between NAA/Cr and DQ,between Cho/Cr and DQ in BGT are higher in regression equation,which are0. 6742 and 0. 5649 respectively. The area under curve( AUC) is 0. 940 and 0. 955 respectively. Conclusion Perinatal asphyxia directly affects the process of myelination and disrupts neuronal and axonal integrity. Perinatal infection only affects the process of myelination in periventricular white matter; The combination of NAA/Cr and Cho/Cr ratios measured in BGT is predictive of neurodevelopmental delay in preterm neonates.
Objective To investigate the influence of perinatal risk factors for metabolite levels in brain of preterm neonates by using multi-voxel magnetic resonance spectroscopy and its predictive value for nervous system developmental delay. Methods A total of 60 preterm neonates at term-equivalent age underwent MRI examination,the MRI examinations including multi-voxel ~1H-MRS and other conventional plain sequences were performed using MAGNETOM Skyra(Siemens Healthcare,Erlangen,Germany),and the Gesell examination was performed at 40 weeks after birth. 46 preterm infants were finally enrolled in this study and were divided into four groups:Group1( n = 12,perinatal normal),Group2( n = 10,perinatal asphyxia),Group3( n = 12,perinatal infection) and Group4( n = 12,perinatal asphyxia and infection). NAA/Cr、Cho/Cr、Lac/Cr ratios were collected from voxels located in the basal ganglia and thalami( BGT) and periventricular white matter( WM). Metabolic values were analyzed by one-way ANOVA across four groups,the correlations between each metabolite and development quotient( DQ) were analyzed by linear regression analysis and evaluate the predictive value for nervous system developmental delay by using receiver operating characteristic curve( ROC). Results Both in BGT and WM regions,the differences of all metabolic values including NAA/Cr,Cho/Cr and Lac/Cr ratios were statistically significant between Group1 and Group2,between Group1 and Group4,between Group3 and Group4. Only in WM region,the difference of Cho/Cr ratio was statistically significant between Group1 and Group3,between Group2 and Group4. The analysis of spearman's correlation demonstrated that DQ had significant correlations with each metabolite in BGT and WM,the determination coefficient between NAA/Cr and DQ,between Cho/Cr and DQ in BGT are higher in regression equation,which are0. 6742 and 0. 5649 respectively. The area under curve( AUC) is 0. 940 and 0. 955 respectively. Conclusion Perinatal asphyxia directly affects the process of myelination and disrupts neuronal and axonal integrity. Perinatal infection only affects the process of myelination in periventricular white matter; The combination of NAA/Cr and Cho/Cr ratios measured in BGT is predictive of neurodevelopmental delay in preterm neonates.
引文
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7 Salmaso N,Jablonska B,Scafidi J,et al.Neurobiology of premature brain injury[J].Nat Neurosci,2014,17:341- 346.
8 Buser JR,Maire J,Riddle A,et al.Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants[J].Ann Neurol,2012,71:93-109.
9 Guo L,Wang D,Bo G,et al.Early identification of hypoxic-ischemic encephalopathy by combination of magnetic resonance (MR) imaging and proton MR spectroscopy[J].Exp Ther Med,2016,12:2835-2842.
10 Hyodo R,Sato Y,Ito M,et al.Magnetic resonance spectroscopy in preterm infants:association with neurodevelopmental outcomes[J].Arch Dis Child Fetal Neonatal Ed,2018,103:F238-F244.
11 Gasparovic C,Caprihan A,Yeo RA,et al.The long-term effect of erythropoiesis stimulating agents given to preterm infants:a proton magnetic resonance spectroscopy study on neurometabolites in early childhood[J].Pediatr Radiol,2018,48:374-382.
12 Taylor MJ,Vandewouw MM,Young JM,et al.Magnetic resonance spectroscopy in very preterm-born children at 4 years of age:developmental course from birth and outcomes[J].Neuroradiology,2018,60:1063-1073.
13 Akasaka M,Kamei A,Araya N,et al.Assessing Temporal Brain Metabolite Changes in Preterm Infants Using Multivoxel Magnetic Resonance Spectroscopy[J].Magn Reson Med Sci,2016,15:187-192.
2 Duerden EG,Taylor MJ,Miller SP.Brain development in infants born preterm:looking beyond injury[J].Semin Pediatr Neurol,2013,20:65-74.
3 Parikh NA.Advanced neuroimaging and its role in predicting neurodevelopmental outcomes in very preterm infants[J].Semin Perinatol,2016,40:530-541.
4 林传家,李寄平,张秀玲,等.婴幼儿发育检查手册[M].北京:北京市儿童保健所,1986.
5 Kendall GS,Melbourne A,Johnson S,et al.White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants[J].Radiology,2014,271:230-238.
6 Tocchio S,Kline-Fath B,Kanal E,et al.MRI evaluation and safety in the developing brain[J].Semin Perinatol,2015,39:73-104.
7 Salmaso N,Jablonska B,Scafidi J,et al.Neurobiology of premature brain injury[J].Nat Neurosci,2014,17:341- 346.
8 Buser JR,Maire J,Riddle A,et al.Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants[J].Ann Neurol,2012,71:93-109.
9 Guo L,Wang D,Bo G,et al.Early identification of hypoxic-ischemic encephalopathy by combination of magnetic resonance (MR) imaging and proton MR spectroscopy[J].Exp Ther Med,2016,12:2835-2842.
10 Hyodo R,Sato Y,Ito M,et al.Magnetic resonance spectroscopy in preterm infants:association with neurodevelopmental outcomes[J].Arch Dis Child Fetal Neonatal Ed,2018,103:F238-F244.
11 Gasparovic C,Caprihan A,Yeo RA,et al.The long-term effect of erythropoiesis stimulating agents given to preterm infants:a proton magnetic resonance spectroscopy study on neurometabolites in early childhood[J].Pediatr Radiol,2018,48:374-382.
12 Taylor MJ,Vandewouw MM,Young JM,et al.Magnetic resonance spectroscopy in very preterm-born children at 4 years of age:developmental course from birth and outcomes[J].Neuroradiology,2018,60:1063-1073.
13 Akasaka M,Kamei A,Araya N,et al.Assessing Temporal Brain Metabolite Changes in Preterm Infants Using Multivoxel Magnetic Resonance Spectroscopy[J].Magn Reson Med Sci,2016,15:187-192.