Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.
Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.
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DOI：
10.3390/metabo12090882
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发表时间：
2022-09-19
期刊：
影响因子：
4.1
通讯作者：
Panigrahy A
中科院分区：
文献类型：
--
作者：
Schmithorst VJ;Adams PS;Badaly D;Lee VK;Wallace J;Beluk N;Votava-Smith JK;Weinberg JG;Beers SR;Detterich J;Wood JC;Lo CW;Panigrahy A
我们使用非侵入性MRI神经血管功能（pnvf）代理评估血管系统提供基线代谢需求的能力，比较儿童和年轻成人先天性心脏病（CHD）患者与正常参考，并将代理与神经认知结果和一氧化氮生物利用度相关。在一项前瞻性单中心研究中，成功地获得了24例CHD患者（年龄= 15.4 ± 4.06岁）和63例正常对照者（年龄= 14.1 ± 3.49岁）的静息态血氧水平依赖（BOLD）和动脉自旋标记（ASL）MRI扫描。Pnvf在体素基础上计算为根据静息状态BOLD采集估计的功能连接强度（FCS）与根据ASL采集估计的局部脑血流量（rCBF）之比的负值。Pnvf用于预测潮气末二氧化碳（PETCO 2）水平，并与BOLD数据估计的水平进行比较。通过鼻测量获得一氧化氮利用率（nNO）。在体素基础上比较CHD患者和正常参考者的Pnvf，并通过NIH神经功能缺损评估Pnvf与一氧化氮可用性和神经认知结果的相关性。使用理论建模，Pnvf显示出对PETCO 2的高度预测性。发现CHD患者的默认模式网络（DMN，包括腹内侧前额叶皮层和后扣带回/楔前叶）、显著性网络（SN，包括前扣带回和背侧前扣带回）和中央执行网络（CEN，包括后顶叶和背外侧前额叶皮层）区域的Pnvf显著降低，在单心室患者中观察到类似的发现。这些脑区以及海马中的Pnvf与神经认知结果呈正相关。同样，Pnvf和一氧化氮的可用性之间的正相关性被发现在额叶DMN和CEN区域，特别是在皮层下区域（壳核）强的相关性。CHD患者Pnvf的降低是由nNO介导的。中介分析进一步支持这些区域的Pnvf降低是CHD患者神经认知结局较差的基础，并与一氧化氮生物利用度相关。神经血管功能受损，可以通过联合动脉自旋标记和BOLD MR成像进行无创评估，是一氧化氮生物利用度依赖性因素，与儿童和年轻成人CHD的不良神经认知结局有关。
We use a non-invasive MRI proxy of neurovascular function (pnvf) to assess the ability of the vasculature to supply baseline metabolic demand, to compare pediatric and young adult congenital heart disease (CHD) patients to normal referents and relate the proxy to neurocognitive outcomes and nitric oxide bioavailability. In a prospective single-center study, resting-state blood-oxygen-level-dependent (BOLD) and arterial spin labeling (ASL) MRI scans were successfully obtained from 24 CHD patients (age = 15.4 ± 4.06 years) and 63 normal referents (age = 14.1 ± 3.49) years. Pnvf was computed on a voxelwise basis as the negative of the ratio of functional connectivity strength (FCS) estimated from the resting-state BOLD acquisition to regional cerebral blood flow (rCBF) as estimated from the ASL acquisition. Pnvf was used to predict end-tidal CO2 (PETCO2) levels and compared to those estimated from the BOLD data. Nitric oxide availability was obtained via nasal measurements (nNO). Pnvf was compared on a voxelwise basis between CHD patients and normal referents and correlated with nitric oxide availability and neurocognitive outcomes as assessed via the NIH Toolbox. Pnvf was shown as highly predictive of PETCO2 using theoretical modeling. Pnvf was found to be significantly reduced in CHD patients in default mode network (DMN, comprising the ventromedial prefrontal cortex and posterior cingulate/precuneus), salience network (SN, comprising the insula and dorsal anterior cingulate), and central executive network (CEN, comprising posterior parietal and dorsolateral prefrontal cortex) regions with similar findings noted in single cardiac ventricle patients. Positive correlations of Pnvf in these brain regions, as well as the hippocampus, were found with neurocognitive outcomes. Similarly, positive correlations between Pnvf and nitric oxide availability were found in frontal DMN and CEN regions, with particularly strong correlations in subcortical regions (putamen). Reduced Pnvf in CHD patients was found to be mediated by nNO. Mediation analyses further supported that reduced Pnvf in these regions underlies worse neurocognitive outcome in CHD patients and is associated with nitric oxide bioavailability. Impaired neuro-vascular function, which may be non-invasively estimated via combined arterial-spin label and BOLD MR imaging, is a nitric oxide bioavailability dependent factor implicated in adverse neurocognitive outcomes in pediatric and young adult CHD.
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影响因子：
1.9
作者：
Dellenbach, Myriam;Zimprich, Daniel
通讯作者：
Zimprich, Daniel
影响因子：
5.7
作者：
Germuska M;Chandler HL;Stickland RC;Foster C;Fasano F;Okell TW;Steventon J;Tomassini V;Murphy K;Wise RG
通讯作者：
Wise RG
影响因子：
4
作者：
Facal, David;Valladares-Rodriguez, Sonia;Juncos-Rabadan, Onesimo
通讯作者：
Juncos-Rabadan, Onesimo
影响因子：
3.3
作者：
Boland, Markus;Stirnberg, Ruediger;Stoecker, Tony
通讯作者：
Stoecker, Tony
影响因子：
5.7
作者：
Germuska, M.;Wise, R. G.
通讯作者：
Wise, R. G.