Advanced Diffusion MRI Applied in Hypoxic-ischemic Neonates

项目总结/摘要 由感染、氧化应激或围产期窒息引起的神经炎症导致缺氧缺血 早产儿脑白质和灰质（WM，GM）损伤 潜在的不可修复的组织损伤，导致终身的神经负担，如脑瘫。习惯性 治疗通常被延迟，直到婴儿发育里程碑失败。共识小组建议， 结合早期神经影像学和发育测试，以便更早地转诊治疗， 这些风险。因此，该领域必须探索更灵敏和更准确的定量方法。 新生儿大脑发育中的脑损伤。一种实用的、非侵入性的显微结构研究技术 脑组织的变化是弥散MRI（dMRI）。F31提案的主要目标是确定， 在足月HIE和早产儿中，无论定量参数是否来自新的先进的 dMRI技术与疾病严重程度相关并预测长期结果。这将得到一个 针对扩散物理学和MRI的教学和实践培训的研究培训计划（导师：詹森）， 新生儿神经发育（导师：Jenkins）和放射学评估（导师：Chatterjee）。项目 通过神经科学、新生儿学和放射学之间的持续合作， 部门，以及其作为Jenkins博士团队中正在进行的方案的一部分的状态，并得到 MUSC生物医学成像中心（CBI）。AIM 1和AIM 2将使用 在50例足月新生儿和23例早产儿中进行弥散峰度成像（DKI）。此外 到DKI，将利用另一种称为纤维球成像（FBI）的技术收集前瞻性dMRI数据， 正在进行的临床影像学方案在30个足月HIE新生儿和23个早产儿。这些dMRI方法将是 比较并结合以预测短期（0 - 3个月）和长期（12和18 - 24个月）发育 常规收集的结果作为标准治疗。更复杂的dMRI分析方法，自动化 纤维定量（AFQ），将在AIM 3中进行研究，以创建受试者特定的白色物质（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，我将学习 扩散以及如何用MRI成像脑水扩散，由量子力学和E & M支持， 我会学习的其次，我将学习神经发育的生理学，缺血性脑血管病的病理生理学， 损伤的脑实质，以及先进的成像生物标志物，包括dMRI的临床重要性， 包括足月新生儿缺氧缺血性脑病和早产儿最后，获得翻译中使用的统计方法的经验， 研究将为我提供适当测试假设驱动研究的知识。与这些 研究和培训机会，以及领先的临床医生和研究人员，他们正在推进临床 通过磁共振成像实践，我的目标是成为一个熟练的翻译磁共振物理学家和独立的调查。

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.