Cerebral Anatomy, Hemodynamics and Metabolism In Single Ventricles: Relationship to Neurodevelopment

 描述（由申请方提供）：在美国，单心室（SV）病变是先天性心脏病（CHD）发病率和死亡率的主要原因。手术重建是分阶段进行的，最终导致最后阶段-Fontan手术。 这些儿童比一般人群和其他形式的CHD有更大的神经发育（ND）缺陷。最终ND结果的一个组成部分是脑血流量（CBF）;我们SV实验室以及文献中的初步数据表明，CBF与ND和认知功能相关。由于各种手术和先天性心脏病引起的血流改变，这些儿童特别容易发生CBF改变。例如，在手术的第一阶段，建立了主动脉到肺动脉的分流;这种从体循环进入低阻力肺循环的途径允许“径流”生理学，潜在地从大脑“窃取”血液。在SV患者中可见的脑异常也与ND有关。有迫切需要了解CBF和大脑异常，因为它涉及到ND在儿童期;这个快速生长阶段可能是特别重要的最终认知功能，不仅有社会/人文的影响，但经济的一个以及。此外，它可能最终导致管理的修改，如手术时机和识别儿童的风险，为不良ND结果实施早期干预。这是一项前瞻性、单中心研究，作为我们在SV患者中几乎完成的NIH RO 1 CBF研究的更新，并试图将脑解剖结构、血流动力学和脑氧代谢（CMRO 2）与ND结局联系起来，使用我们的原始患者队列作为基础。本研究将利用磁共振成像（MRI）测量血流，并通过相位对比MRI、动脉自旋标记和解剖成像（如T1加权序列）可视化大脑解剖结构。利用磁共振成像（一名合作研究者新开发的技术）的MRI将评估CMRO 2。这种MRI功能的组合为一项研究中的全面脑评估提供了独特的机会;通过将其与ND测试相结合，本研究将通过召回我们最初的NIH CBF研究中的患者进行MRI和ND，与原始NIH资助和当前提案的数据相关联，确定CBF和脑异常与ND结局的关系。这也将允许确定SV患者的CBF和脑异常如何随时间演变。将招募额外的SV患者和正常对照以丰富人群。本研究还将确定CMRO 2与脑病变和ND结局之间的关系。本研究的影响对于优化SV患者的ND非常重要。如果要改善ND，必须获得有关脑解剖、血流动力学和代谢对ND影响的关键信息。更新将通过有效利用我们多学科团队的专业知识来填补关键的知识空白。这项研究的结果将提供关键数据，为未来改善SV中ND结局的干预性试验提供信息。

 DESCRIPTION (provided by applicant): Single ventricle (SV) lesions are the leading cause of morbidity and mortality from congenital heart disease (CHD) in the United States. The surgical reconstruction is performed in stages ultimately leading to the final stage - the Fontan operation. These children have greater neurodevelopmental (ND) deficits than the general population and other forms of CHD. One component to ultimate ND outcome is cerebral blood flow (CBF); preliminary data from our lab in SV as well as in the literature suggests that CBF is related to ND and cognitive function. These children are especially at risk for altered CBF because of the altered blood flow caused by the various surgeries and congenital heart lesion. For example, in the first stage of surgery, an aortic to pulmonary shunt is created; this access to the low resistance pulmonary circulation from the systemic circulation allows for a "runoff" physiology, potentially "stealing" blood away from the brain. Brain abnormalities, which can be seen in SV patients, have also been linked to ND. There is a pressing need to understand CBF and brain abnormalities as it relates to ND in childhood; this rapid growth stage may be especially important to ultimate cognitive function which not only has a social/humanistic impact but an economic one as well. In addition, it may ultimately lead to modifications in management such as timing of surgery and identifying children at risk for poor ND outcome to implement early interventions. This is a prospective, single center study submitted as a renewal of our nearly completed NIH RO1 CBF study in SV patients and seeks to relate cerebral anatomy, hemodynamics and cerebral oxygen metabolism (CMRO2) to ND outcome, using our original patient cohort as a basis. This study will utilize magnetic resonance imaging (MRI) to measure blood flow and visualize cerebral anatomy by phase contrast MRI, arterial spin labeling, and anatomic imaging such as T1 weighted sequences. MRI utilizing susceptometry, a newly developed technique by one of the co-investigators, will assess CMRO2. This combination of MRI capabilities offers a unique opportunity for a comprehensive cerebral assessment in one study; by combining this with ND testing, this study will determine the relationship of CBF and brain abnormalities to ND outcomes by recalling patients from our original NIH CBF study to undergo an MRI and ND, correlating with data from the original NIH grant and the current proposal. This will also allow for determining how CBF and brain abnormalities evolve in SV patients over time. Additional SV patients and normal controls will be recruited to enrich the population. This study will also determine the relationship between CMRO2 with brain lesions and ND outcome. The impact of this study is important to optimize ND in SV patients. Critical information on the effect of cerebral anatomy, hemodynamics and metabolism on ND must be obtained if it is to improve. The renewal will fill key knowledge gaps by efficiently capitalizing n the expertise of our multidisciplinary team. The findings from this study will provide critical dat that will inform a future interventional trial on improving ND outcomes in SV.