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

单心室的大脑解剖学、血流动力学和代谢：与神经发育的关系

• 批准号: 9100885
• 负责人: Mark A Fogel
• 金额: $ 63.26万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9100885
• 关键词: 9 year old; Affect; Age; Anatomy; Behavioral; Blood; Blood Circulation; Blood flow; Brain; Carbon Dioxide; Cause of Death; Cerebrovascular Circulation; Cerebrum; Child; Child health care; Childhood; Cognitive; Common Ventricle; Complex; Data; Diffusion; Disease; Early Intervention; Economics; Fontan Procedure; Future; General Population; Grant; Health; Heart; Hypercapnia; Image; Intervention Trial; Knowledge; Lead; Lesion; Link; Literature; Lung; Magnetic Resonance Imaging; Measures; Mental Retardation; Metabolism; Modification; Morbidity - disease rate; Neurodevelopmental Deficit; Operative Surgical Procedures; Outcome; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Palliative Surgery; Patients; Phase; Physiology; Population; Pulmonary Circulation; Pulmonary artery structure; Pump; Recruitment Activity; Reporting; Research Personnel; Resistance; Risk; Series; Shunt Device; Social Impacts; Societies; Special Education; Spin Labels; Staging; Stress; Superior vena cava structure; Techniques; Testing; Theft; Time; United States; United States National Institutes of Health; Ursidae Family; Venous; Venous Pressure level; Weight; base; behavior test; brain abnormalities; cerebral hemodynamics; cognitive function; cohort; congenital heart disorder; economic impact; hemodynamics; improved; intervention program; member; metabolic rate; mortality; multidisciplinary; neurodevelopment; operation; prospective; rapid growth; reconstruction; response; social

 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.

 描述（由适用提供）：单一通风（SV）病变是美国先天性心脏病（CHD）发病率和死亡率的主要原因。手术重建是在最终导致最终阶段的Fontan操作的阶段进行的。 这些儿童的神经发育（ND）比一般人群和其他形式的CHD定义更大。最终和最终结果的一个组成部分是脑血流（CBF）；来自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变引起的血液流动改变，这些儿童尤其有改变CBF的风险。例如，在手术的第一阶段，会产生主动脉到肺分流。从全身循环中获得低耐药性肺循环的通道允许“径流”生理学，可能会“偷走”血液从大脑中流离失所。在SV患者中可以看到脑异常，也已与ND有关。迫切需要了解CBF和脑部异常，因为它与童年时期有关。这个快速增长的阶段对于最终的认知功能可能尤其重要，不仅具有社会/人文影响，而且具有经济影响。此外，它最终可能会导致管理的修改，例如手术时间和确定ND不良结果的风险以实施早期干预措施的风险。这是一项前瞻性单中心研究，作为我们在SV患者中近乎完成的NIH RO1 CBF研究的续签，并试图使用我们的原始患者组成的基础，以将大脑解剖学，血液动力学和脑氧代谢（CMRO2）联系起来。这项研究将利用磁共振成像（MRI）来测量血流，并通过相对比MRI，动脉自旋标记和解剖成像（例如T1加权序列）来可视化脑解剖学。 MRI利用苏斯托术的MRI是一项共同研究器的新技术，将评估CMRO2。在一项研究中，MRI功能的这种结合为全面的脑评估提供了独特的机会。通过将其与ND测试相结合，这项研究将通过召回我们原始NIH CBF研究中的患者进行MRI和ND，确定CBF和脑异常与ND结局的关系，与原始NIH赠款和当前建议的数据相关。这也将允许确定随着时间的推移，SV患者的CBF和脑异常如何发展。将招募其他SV患者和正常对照，以丰富人口。这项研究还将确定CMRO2与脑损伤和ND结局之间的关系。这项研究的影响对于优化SV患者的ND很重要。有关脑解剖学，血液动力学和代谢对ND的影响的关键信息，必须获得改善。续订将通过有效地介绍我们多学科团队的专业知识来填补关键知识空白。这项研究的发现将提供关键的DAT，该数据将为以后的介入试验提供有关改善SV中ND结果的未来试验。