High Fidelity Diffusion MRI for Children with Cerebral Palsy in Stem Cell Therapy

描述（由申请人提供）：最近出现的扩散张量成像（DTI）提供了一种新的对比机制，通过水扩散特性来研究人脑中的白色物质发育和完整性及其对神经元功能的影响。由于其独特的敏感性，DTI最有价值和最合适的应用之一是研究儿童大脑发育，因为许多儿童衰弱性疾病都起源于白色物质异常和损伤。例如，脑性麻痹（CP）是由子宫内或围产期运动通路损伤引起的，是儿童期最普遍的运动障碍，每1，000名活产婴儿中就有2至3人受到影响。其明确的白色基质病理学将受益于DTI提供的唯一白色物质表征。然而，目前的DTI实践缺乏足够的空间分辨率和随后的定量一致性来表征CP中复杂运动通路的损伤及其在治疗期间的恢复。有许多因素导致这种不足，其中主要是实现高空间分辨率的技术限制，DTI脉冲序列中固有的系统失真，其在张量估计中引入失真和误差，以及由于大的扩散加权梯度而对全局和局部运动的灵敏度提高，其进一步使患者群体中的实际效用复杂化。这些缺陷在儿童等弱势群体中尤为严重。在这项提案中，我们的目标是通过开发创新的采集解决方案来解决目前的这些限制，以实现急需的空间分辨率和保真度，并随后应用我们创新的DTI采集方法来更好地表征CP儿童的大脑连接，利用我们与一个长期成功的临床项目的强大合作伙伴关系，通过脐带血（UCB）输注。具体而言，我们建议：1）实现更好地描绘复杂的白色物质纤维结构所需的高空间分辨率，2）实现高空间保真度以改善张量估计和与神经解剖学的共配准，3）实现大大降低的运动灵敏度以改善儿科患者群体中的实用性，四、获取和开发CP中的小儿脑连接图，以研究UCB干细胞治疗期间儿童运动通路和功能的损伤和恢复疗法我们预计，我们的创新采集方法将大大提高空间分辨率和定量 DTI测量的一致性，这可以提高我们对干细胞治疗前景的理解，并帮助设计CP儿童的最佳治疗方案。我们的新方法也可能在基础和临床神经科学中得到更广泛的应用。 公共卫生相关性：扩散张量成像（DTI）对水扩散特性敏感，为研究人员和临床医生提供了一个新的维度来研究白色物质的微观结构，发育和病理。然而，所得到的大脑连接图通常缺乏足够的空间分辨率和随后的定量一致性，导致对白色物质变化的评估不足，并且诊断大脑疾病和研究潜在疾病机制的临床意义不大。我们在这里提出了一个集成的DTI采集方法，解决了空间分辨率，空间保真度和运动灵敏度的三个紧迫的限制，阻碍了我们的调查在发展中的大脑。此外，我们将在高分辨率DTI中应用新的采集方法，以绘制脑瘫儿童（CP）的复杂大脑连接，利用我们正在进行的努力，通过脐带血（UCB）输注在脑瘫儿童中使用创新和有前途的干细胞治疗。我们预计，我们的项目将提供一个强大的技术基础，以更好地表征CP中复杂运动通路的连接障碍，并评估其在干细胞治疗期间的恢复。DTI空间分辨率的大幅提高也将在转化神经科学中找到更广泛的适用性。

DESCRIPTION (provided by applicant): The recent emergence of diffusion tensor imaging (DTI) provides a new contrast mechanism through water diffusion characteristics to investigate the white matter development and integrity in the human brain, and their impact on neuronal functions. Given its unique sensitivity, one of the most valuable and fitting applications of DTI i the investigation of developing brains in children, as many debilitating diseases in children are originated from white matter abnormalities and injuries. For example, Cerebral Palsy (CP), which results from in utero or perinatal injuries to motor pathways, is the most prevalent motor disorder of childhood, affecting 2 to 3 out of every 1,000 live births. Its well-defined white mattr pathology would benefit from the exclusive white matter characterization provided by DTI. However, the current DTI practice lacks sufficient spatial resolvability and subsequent quantitative consistency to characterize the impairment of the complex motor pathway in CP and its recovery during treatment. There are many contributing factors to this inadequacy, chief among them are the technical limitations in achieving high spatial resolution, the systematic distortions inherent in the DTI pulse sequences that introduce distortions and errors in tensor estimation, and the heightened sensitivity to global and local motions due to large diffusion weighting gradients that further complicate the practical utility in patient populations. These drawbacks are exacerbated especially in vulnerable populations such as children. In this proposal, we aim to address these current limitations by developing innovative acquisition solutions to achieve the much needed spatial resolution and fidelity, and to subsequently apply our innovative DTI acquisition methodology to better characterize the brain connectivity in children with CP, leveraging our strong partnership with a long-standing and successful clinical program using an innovative and promising stem cell therapy through umbilical cord blood (UCB) infusion. Specifically, we propose to: 1) achieve high spatial resolution necessary to better delineate complex white matter fiber structure, 2) achieve high spatial fidelity to improve tensor estimation and co-registration with neuroanatomy, 3) achieve greatly reduced motion sensitivity to improve practical utility in pediatric patient populations, 4) acquire and develop pediatric brain connectivity maps in CP to investigate the impairment and recovery of motor pathway and functions in children during UCB stem cell therapy. We anticipate that our innovative acquisition methodology will greatly increase the spatial resolvability and quantitative consistency of DTI measures, which can improve our understanding on the promising effects of stem cell therapy and help design the best treatment plan for children with CP. It is also likely that our new methodology will find broader application in basic and clinical neurosciences at large. PUBLIC HEALTH RELEVANCE: Sensitive to water diffusion characteristics, diffusion tensor imaging (DTI) provides researchers and clinicians a new dimension to study white matter microstructure, development and pathology. However, the resultant maps on brain connectivity often lacks sufficient spatial resolvability and subsequent quantitative consistency, leading to inadequate assessment of white matter changes and less clinically meaningful indices to diagnose brain disorders and investigate underlying disease mechanisms. We propose here an integrated DTI acquisition methodology that addresses three pressing limitations in spatial resolution, spatial fidelity, and motion sensitivity that hamper our investigation in developing brains. Further, we will apply the new acquisition methodology in high-resolution DTI to map the complex brain connectivity in children with Cerebral Palsy (CP), taking advantage of our ongoing effort using an innovative and promising stem cell therapy through umbilical cord blood (UCB) infusion in children with CP. We anticipate that our project will provide a robust technical foundation to better characterize the connectivity impairment in complex motor pathways in CP, and assess their recovery during stem cell therapy. The greatly improved spatial resolvability for DTI will also find broader applicability in translational neuroscience.