Advanced Diffusion MRI Applied in Hypoxic-ischemic Neonates

项目摘要/摘要 感染、氧化应激或围产期窒息引起的神经炎症导致缺氧缺血 足月儿脑病(HIE)与早产儿白质、灰质损伤 潜在的不可修复的组织损伤，招致终生的神经负担，如脑瘫。康复训练 治疗经常被推迟，直到婴儿未能达到发育里程碑。协商一致的小组建议 结合早期神经成像和发育测试进行早期转诊治疗，可能会缓解 这些风险。因此，该领域探索更灵敏和准确的量化方法至关重要。 发育中的新生儿大脑中的脑损伤。一种实用的非侵入性微结构研究技术 脑组织的变化是弥散磁共振成像(DMRI)。这份F31提案的主要目标是确定， 在足月缺氧缺血性脑病和早产儿中，无论定量参数是否来自新的晚期 DMRI技术与疾病严重程度相关，并预测长期结果。这将由一个 针对扩散物理和磁共振成像教学和实践培训的研究培训计划(导师：Jensen)， 新生儿神经发育(导师：詹金斯)和放射学评估(导师：查特吉)。项目 通过神经科学、新生医学和放射学之间的持续合作，增强了可行性 部门，以及它作为詹金斯博士团队正在进行的方案的一部分的地位，并得到 南加州大学生物医学成像中心(CBI)。AIM 1和AIM 2将使用 对50例足月HIE和23例早产儿进行了弥散峰度成像(DKI)检查。此外 对于DKI，将使用另一种称为纤维球成像(FBI)的技术来收集预期的dMRI数据 30例足月HIE新生儿和23例早产儿正在进行的临床影像检查。这些dMRI方法将是 比较和结合预测短期(0-3个月)和长期(12-24个月)发育 结果通常被收集为标准护理。更复杂的dMRI分析方法，自动化 将在AIM 3中研究纤维量化(AFQ)，以创建特定于受试者的白质(WM)束轮廓。 有了这些研究目标，我将实现三个相互关联的培训目标。首先，我将在物理学方面进行培训 扩散以及脑水扩散是如何用磁共振成像的，由量子力学和EM&M支持 我会学习的。第二，我将学习神经发育的生理学，缺血的病理生理学。 脑实质损伤，以及包括磁共振成像在内的先进成像生物标记物的临床重要性 足月缺氧缺血性脑病和早产儿。最后，获得在翻译中使用的统计方法的经验 研究将为我提供适当检验假设驱动研究的知识。有了这些 研究和培训机会与领先的临床医生和研究人员一起推进临床 通过磁共振成像练习，我的目标是成为一名熟练的翻译MR物理学家和独立调查员。

PROJECT SUMMARY/ABSTRACT Neuroinflammation caused by infection, oxidative stress or perinatal asphyxia leads to hypoxic ischemic encephalopathy (HIE) in term infants and white and gray matter (WM, GM) injury in preterm infants with potentially irreparable tissue damage, incurring life-long neurological burdens such as cerebral palsy. Habilitative therapies are often delayed until infants fail developmental milestones. A consensus panel recommended combined early neuroimaging and developmental testing for earlier referrals to therapy, potentially mitigating these risks. Therefore, it is essential the field explores methods for more sensitive and accurate quantification of brain injury in the developing neonatal brain. A practical and non-invasive technique to study microstructural tissue changes in the brain is diffusion MRI (dMRI). The primary goal of this F31 proposal is to determine, in term HIE and preterm infants, whether or not quantitative parameters derived from novel advanced dMRI techniques correlate to disease severity and predict long-term outcome. This will be supported by a research training plan targeted at didactic and hands-on training in diffusion physics and MRI (mentor: Jensen), neonatal neurodevelopment (mentor: Jenkins) and radiological assessment (mentor: Chatterjee). Project feasibility is enhanced through on-going collaborations among the Neuroscience, Neonatology and Radiology divisions, as well as its status as part of an on-going protocol within Dr. Jenkins’ team with assistance from the Center for Biomedical Imaging (CBI) at MUSC. AIM 1 and AIM 2 will analyze existing dMRI data using a technique known as diffusional kurtosis imaging (DKI) acquired in 50 term HIE and 23 preterm infants. In addition to DKI, prospective dMRI data will be collected utilizing another technique known as fiber ball imaging (FBI) in ongoing clinical imaging protocols in 30 term HIE neonates and 23 preterm infants. These dMRI methods will be compared and combined to predict short-term (0-3 month) and long-term (12 and 18-24 month) developmental outcomes routinely collected as standard-of-care. A more sophisticated dMRI analysis approach, automated fiber quantification (AFQ), will be investigated in AIM 3 to create subject specific white matter (WM) tract profiles. With these research aims, I will fulfill three, interconnected training goals. First, I will train in the physics of diffusion and how brain water diffusion is imaged with MRI, supported by the quantum mechanics and E&M that I will study. Second, I will learn about the physiology of neurodevelopment, the pathophysiology of ischemic injury to the brain parenchyma, and the clinical importance of advanced imaging biomarkers, including dMRI, in both term HIE and preterm infants. Finally, gaining experience in the statistical methods used in translational research will provide me with the knowledge to appropriately test hypothesis driven research. With these research and training opportunities alongside leading clinicians and researchers who are advancing clinical practice through MR imaging, I aim to become an adept translational MR physicist and independent investigator.