Quantitation of Insult and Injury to the Preterm Brain

早产儿大脑损伤和损伤的定量

• 批准号: 7188834
• 负责人: ADRE Jacques DU PLESSIS
• 金额: $ 12.42万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7188834
• 关键词: Address; Age; Area; Award; Baroreflex; Blood; Blood Circulation; Blood Pressure; Brain; Brain Injuries; Cephalic; Cerebral hemisphere; Cerebrum; Clinical Trials; Collaborations; Contralateral; Data; Databases; Development; Diagnosis; Diffusion; Disruption; Educational process of instructing; Exposure to; Failure; Fiber; Frequencies; Future; Goals; Growth; Hemoglobin; Homeostasis; Hour; Hypoxia; Impairment; Infant; Injury; Lesion; Life; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Mentors; Modeling; Multiparametric Analysis; Near-Infrared Spectroscopy; Neonatal; Neurology; Newborn Infant; Outcome; Perfusion; Phase; Predisposing Factor; Pregnancy; Premature Infant; Prevention; Process; Research; Research Personnel; Research Project Grants; Risk; Severities; Specialist; Supratentorial; Systems Analysis; Techniques; Testing; Time; Tissues; Training; Training Programs; Ultrasonography; Urination; Week; Work; base; career; cerebrovascular; day; hemodynamics; indexing; innovation; interest; intraventricular hemorrhage; neuroprotection; patient oriented research; postnatal; pressure; response; skills; tool

DESCRIPTION (provided by applicant): Career development goals: To develop a model training program for mentoring and promoting patient-oriented research focused on injury to the immature brain and its prevention. Research goals: To develop in premature infants at risk for brain injury quantitative functional measures of cerebrovascular impairment and insult, and quantitative structural measures of the response to brain injury. Research project: This project combines two Specific Aims from ongoing research projects with the goal of training young researchers in quantitation of cerebral insult and outcome in neonatal neurology. The project will test two major hypotheses: 1) Transfer function analysis of continuously measured changes in blood pressure and cerebral perfusion (using near infrared spectroscopy; NIRS) will identify significant periods of pressure-passive cerebral perfusion preceding germinal matrix-intraventricular hemorrhage (GM-IVH) in premature infants; and that a multiparametric analysis will identify systemic hemodynamic factors that predispose to unstable cerebral hemodynamics. Time-locked continuous recording of systemic and cerebral hemodynamic changes over the first 5 days (i.e., risk period for GM-IVH) combined with brief 4-hourly truncated cranial ultrasound studies will be used to explore hemodynamic antecedents of GM-IVH. 2) Quantitative MRI measures in ex-preterm infants with either cerebral or cerebellar injury will demonstrate remote regional disturbances in development of projection areas of the contralateral cerebellar or cerebral hemispheres. Using a large existing MRI database and ongoing study recruitment, we will measure regional volumetric brain growth (by parcellated 3D-MRI) in remote projection areas, measure connectivity (diffusion tensor-based fiber tractography) between regions of injury and expected projection areas. Together these goals address a major void in neonatal neurology research, i.e., an inability to identify precise hemodynamic insults leading to injury, here specifically GM-IVH, and a lack of measurable regional structural responses of the immature brain to injury. This proposal seeks to develop these tools, and the specialists in their use, urgently needed for future clinical trials of neuroprotection. The aims of this mentoring award will be met by providing the candidate with the time to develop in trainees an understanding of brain injury mechanisms in the newborn, teaching them the basic skills of patient-oriented research in the newborn, and cultivating the necessary analytic skills for their own independent research and future collaborations in clinical trials of neuroprotection.

描述（由申请人提供）：职业发展目标：制定模型培训计划，用于指导和促进针对患者的研究，重点是对未成熟大脑及其预防的伤害。研究目标：在脑损伤脑损伤损伤和侮辱的脑损伤定量功能测量中发展的早产婴儿，以及对脑损伤反应的定量结构测量。研究项目：该项目结合了正在进行的研究项目的两个具体目标，目的是培训年轻研究人员对新生儿神经病学中脑损伤和结果的定量。该项目将检验两个主要的假设：1）在血压和脑灌注的连续测量变化（使用近红外光谱； NIRS）的连续测量变化的转移功能分析将确定较大的压力性脑灌注，先前是生发性基质基质基质 - 触发性 - 触发性脑部出血（GM-IVH），在中早产辅助师中；并且多参数分析将确定易于脑血液动力学不稳定的全身血液动力学因素。在最初5天（即GM-IVH的风险周期）以及短暂的4小时截断的颅骨超声研究中，全身性和脑血液动力学变化的时间锁定连续记录将用于探索GM-IVH的血液动力学前体。 2）脑或小脑损伤的前先驱婴儿的定量MRI度量将在对侧小脑或大脑半球的投射区域发展中表现出遥远的区域干扰。使用大量现有的MRI数据库和正在进行的研究招募，我们将在远程投影区域测量区域体积大脑的生长（通过3D-MRI），衡量损伤区域和预期投影区域之间的连通性（基于扩散张量的基于张量的纤维拖拉术）。这些目标共同解决了新生神经病学研究中的主要空隙，即无法识别导致损伤的精确血液动力学损伤，特别是GM-IVH，以及缺乏未成熟大脑对损伤的可测量的区域结构反应。该建议旨在开发这些工具以及专家使用的专家，迫切需要对神经保护的临床试验。通过为候选人提供对新生儿中脑损伤机制的理解，教给他们新生儿中面向患者的研究的基本技能，并培养其独立研究和未来在神经保护临床试验中的未来合作的必要分析技能的基本技能，从而使他们有时间在受训者中了解这一指导奖的目标。