Prognostic MRS in neonatal encephalopathy: closer to generalizability.
Prognostic MRS in neonatal encephalopathy: closer to generalizability.
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DOI：
10.1038/s41390-021-01803-0
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Waddell J
中科院分区：
文献类型：
--
作者：
Waddell J
在最新一期的儿科研究中，Barta 等人。 1 在题为“新生儿缺氧缺血性脑病中质子磁共振波谱的预测性能和代谢动力学”的手稿中展示了从患有缺氧缺血性脑病（HIE）的婴儿在生命的前两周获得的深部灰质的 1H MRS 数据。在出生后的前 2 周对代谢物 N-乙酰天门冬氨酸 (NAA)、肌酸 (Cr) 和肌醇 (mI) 进行定量，并计算 NAA/Cr 和 mI/NAA 比率，以确定这些比率是否是 18-26 个月龄结果的有用预测因子。婴儿接受低温治疗。使用 MRS 进行可靠的结果预测的效用很高，可以提高临床试验的效率，因为它是非侵入性的，可以预测一系列损伤后时间间隔的长期结果。然而，分析的大脑区域、孕龄、数据采集时的产后年龄以及围绕数据采集的技术细节的差异使得跨研究建立可靠的预后指标变得困难。 HIE 是一种多相脑损伤，其特征是大脑中急性和长期的代谢失调。氧气和血流的急剧丧失会破坏线粒体功能，耗尽 ATP 和磷酸肌酸，从而减少通常为基本细胞功能提供代谢支持的磷酸盐的供应。 2, 3 血流损失和缺氧会导致无氧代谢的最终产物乳酸积聚，因为它无法被血流分解代谢或清除。 4 这种乳酸的急性峰值可以在复苏过程中迅速清除，通常在数小时内恢复到正常水平，但在生命的最初几天可能会出现持续较高的脑乳酸水平，并且很可能表明严重损伤和预后不良。 5 在涉及基底神经节或丘脑损伤的中度至重度 HIE 病例中，局部脑乳酸水平在数天至数周内持续升高。 5、6 NAA 是由神经元线粒体中的乙酰辅酶 A 合成的，在健康发育的大脑中，NAA 逐渐增加（参见参考文献 4、7）。当发育性脑损伤后 NAA 仍然较低时，结果通常很差。 8 HIE 仔猪模型中的 Lac/NAA 比率与损伤后 48 小时内基底神经节和丘脑的细胞死亡和小胶质细胞活化呈强正相关。 9 该比率是否在以后的时间点和不同的损伤表现（例如分水岭区域）中仍具有预测作用尚不清楚，但为 MRS 和特定代谢物比率的潜在机制解析提供了重要的见解。 mI 在早期发育阶段非常高，随着孕龄和产后年龄的增长而降低。 7、 10 mI 是一种渗透剂，也是肌醇合成脂质的前体，可调节膜动力学。 11 巴塔等人。 1 发现，在出生后 14 天内获取数据时，NAA/Cr 和 mI/NAA 比率都可以预测结果。在表现出良好结局的婴儿中，胎龄也会影响这些代谢物比率，与健康新生儿类似，随着发育的进展，NAA/Cr 比率增加，而 mI/NAA 比率下降。 10 对于那些面临不良结果的人来说，这种关系并不明显。晚孕龄婴儿的 NAA 和 Cr 均较高，但低于成人中观察到的水平。 10 作者的结论是，当 HIE 不太严重时，可以观察到这些比率的典型发育进程，而更严重的损伤会破坏这种发育进程。 NAA/Cr 的比率并不总是 HIE 结果的明确预测因子。 12 柴崎等人。 12 没有找到...
In the current issue of Pediatric Research, Barta et al. 1 present 1H MRS data of deep gray matter acquired from infants suffering hypoxic–ischemic encephalopathy (HIE) across the first 2 weeks of life in the manuscript entitled “Predictive performance and metabolite dynamics of proton MR spectroscopy in neonatal hypoxic-ischemic encephalopathy.” Metabolites N-acetyl-aspartate (NAA), creatine (Cr), and myo inositol (mI) were quantified in the first 2 weeks of life, and the NAA/Cr and mI/NAA ratios were calculated to determine whether these ratios are useful predictors of outcome at 18–26 months of age. Infants were treated with therapeutic hypothermia. The utility of a reliable predictor of outcome using MRS is high, increasing efficiency of clinical trials, since it is non-invasive and can predict long-term outcomes across a range of post-injury intervals. However, differences in brain region (s) analyzed, gestational age, postnatal age at the time of data acquisition, and technical details surrounding data acquisition have made establishment of a reliable prognostic indicator across studies elusive. HIE is a multi-phase brain injury characterized by acute and protracted metabolic dysregulation in brain. Acute loss of oxygen and blood flow disrupts mitochondrial function, depleting both ATP and phosphocreatine, reducing supply of phosphates that normally provide metabolic support for basic cellular functions. 2, 3 Loss of blood flow and hypoxia cause the end product of anaerobic metabolism, lactate, to accumulate as it cannot be catabolized or cleared by blood flow. 4 This acute spike in lactate can be quickly cleared during resuscitation and typically resolves to normal levels within hours, but persistently high cerebral lactate can occur over the initial days of life, and is very likely to indicate severe injury and poor outcome. 5 In cases of moderate to severe HIE that involve injury of the basal ganglia or thalamus, local cerebral lactate levels remains elevated for days to weeks. 5, 6 NAA is synthesized from acetyl-CoA in neuronal mitochondria, and in the healthy developing brain, NAA gradually increases (reviewed in refs. 4, 7). When NAA remains low after developmental brain injury, outcomes are typically poor. 8 The Lac/NAA ratio in a piglet model of HIE was strongly positively correlated with cell death and microglial activation in the basal ganglia and thalamus in the first 48 h after injury. 9 Whether this ratio remains predictive at later timepoints and in different manifestations of injury (eg, watershed regions) is unclear, but provides an important insight into the potential mechanistic resolution of MRS and specific metabolite ratios. mI is very high in early development, decreasing with both gestational and postnatal age. 7, 10 mI is an osmolyte and a precursor for lipid synthesis from inositol, regulating membrane dynamics. 11 Barta et al. 1 found that both the NAA/Cr and mI/NAA ratios can predict outcomes when data are acquired within the first 14 days of life. In infants that exhibit good outcome, gestational age also contributes to these metabolite ratios, similar to healthy newborn infants, where the NAA/Cr ratio increases, while the mI/NAA ratio decreases as development progresses. 10 No such relationship was evident in those facing a poor outcome. Both NAA and Cr are higher in infants born at later gestational ages, but lower than levels observed in the adult. 10 The authors conclude that when HIE is less severe, the typical developmental progression of these ratios can be observed, while more severe injury disrupts this developmental progression. The ratio of NAA/Cr is not always a clear predictor of outcome in HIE. 12 Shibasaki et al. 12 did not find …
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