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

 描述(由申请人提供)：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。外科重建是分阶段进行的，最终导致最后一个阶段--丰坦手术。 这些儿童的神经发育(ND)缺陷比普通人群和其他形式的CHD更严重。最终ND结局的一个组成部分是脑血流量(CBF)；来自我们在SV的实验室以及文献中的初步数据表明，CBF与ND和认知功能有关。由于各种手术和先天性心脏病引起的血流改变，这些儿童特别有可能发生脑血流量改变。例如，在手术的第一阶段，建立了主动脉到肺的分流；这种从体循环进入低阻肺循环的途径允许生理上的“径流”，潜在地从大脑“窃取”血液。脑部异常，可以在SV患者中看到，也与ND有关。迫切需要了解CBF和大脑异常，因为它与儿童时期的ND有关；这一快速发育阶段可能对最终的认知功能特别重要，这不仅具有社会/人文影响，而且还具有经济影响。此外，这最终可能导致管理上的改进，如手术时机和识别有不良ND结局风险的儿童，以实施早期干预。这是一项前瞻性的单中心研究，是我们在SV患者中几乎完成的NIH RO1 CBF研究的更新，试图以我们最初的患者队列为基础，将脑解剖、血流动力学和脑氧代谢(CMRO2)与ND结果联系起来。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)来可视化大脑解剖结构。利用磁感应强度测量的磁共振成像将评估CMRO2，这是一项由合作研究人员开发的新技术。这种MRI能力的结合为在一项研究中进行全面的大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研究中的患者接受MRI和ND，从而确定CBF和脑异常与ND结果的关系，并将原始NIH拨款和当前提案中的数据关联起来。这也将允许确定脑血流和脑异常是如何随着时间的推移在SV患者中演变的。将招募更多的SV患者和正常对照来丰富人口。这项研究还将确定CMRO2与脑损害和ND预后的关系。这项研究的影响对优化SV患者的ND具有重要意义。如果要改善ND，必须获得有关脑解剖、血流动力学和新陈代谢影响的关键信息。更新将通过有效地利用我们多学科团队的专业知识来填补关键的知识空白。这项研究的发现将提供关键的数据，为未来关于改善SV的ND结局的介入试验提供信息。

 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.