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

干细胞治疗中脑瘫儿童的高保真扩散 MRI

• 批准号: 8289889
• 负责人: ALLEN W SONG
• 金额: $ 34.13万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289889
• 关键词: Address; Affect; Algorithms; Area; Behavior; Brain; Brain Stem; Brain region; Cells; Cerebral Palsy; Cerebrum; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Collaborations; Complex; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Fiber; Foundations; Functional Magnetic Resonance Imaging; Hemiplegia; Human; Image; Impairment; Individual; Infusion procedures; Injury; Internal Capsule; Investigation; Lateral; Live Birth; Maps; Measures; Methodology; Morphologic artifacts; Motion; Motivation; Motor; Motor Pathways; Neuroanatomy; Neuronal Plasticity; Neurons; Neurosciences; Pathology; Patients; Perinatal; Physiologic pulse; Placebo Effect; Process; Recovery; Research Personnel; Resolution; Solutions; Spectrum Analysis; Stem cells; Structure; Techniques; Three-Dimensional Imaging; Time; Translations; Treatment Effectiveness; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Vulnerable Populations; Weight; awake; base; behavior measurement; brain disorder diagnosis; childhood motor disorders; clinical application; design; diffusion anisotropy; improved; improved functioning; in utero; indexing; innovation; magnetic field; millimeter; motion sensitivity; patient population; programs; reconstruction; relating to nervous system; repaired; statistics; stem; stem cell therapy; translational neuroscience; treatment planning; water diffusion; white matter; white matter change

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.

描述（由申请人提供）：扩散张量成像（DTI）的最新出现通过水扩散特征提供了一种新的对比机制，以研究人脑中的白质发育和完整性及其对神经元功能的影响。鉴于其独特的敏感性，DTI I最有价值，最合适的应用之一是对儿童发育的调查，因为儿童中许多令人衰弱的疾病源自白质的异常和伤害。例如，脑瘫（CP）是由于子宫或围产期损伤导致的，是童年时期最普遍的运动障碍，每1000例活生生中有2至3个。其定义明确的白色MATTR病理学将受益于DTI提供的专有的白质特征。然而，当前的DTI实践缺乏足够的空间分解性和随后的定量一致性，无法表征CP中复杂的电动途径及其在治疗过程中的恢复的损害。这种不足的原因有许多贡献因素，其中最主要的是实现高空间分辨率的技术局限性，DTI脉冲序列中固有的系统扭曲固有的张力和张力估计中的错误以及由于对全球和局部动力的敏感性增加而导致大量扩散梯度使体重增加的病人的敏感性更大。这些缺点尤其是在诸如儿童之类的脆弱人群中加剧。 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.具体而言，我们建议：1）实现更好地描绘复杂的白质纤维结构所需的高空间分辨率，2）实现高空间保真度，以改善张量的估计和与神经术的共同注册，3）大大提高运动敏感性，以提高运动疗法的运动疗法，并在儿童脑中的恢复性和培养性方面提高培养性，4）4）恢复型脑部的恢复性，4）在UCB干细胞疗法期间儿童的功能。我们预计我们的创新采集方法将大大提高空间可分胜性和定量性 DTI措施的一致性，这可以提高我们对干细胞疗法的有希望影响的理解，并帮助设计CP儿童的最佳治疗计划。我们的新方法也很可能会在整个基本和临床神经科学中发现更广泛的应用。 公共卫生相关性：对水扩散特征敏感，扩散张量成像（DTI）为研究人员和临床医生提供了研究白质微结构，发育和病理学的新维度。但是，大脑连通性的最终图通常缺乏足够的空间共振性和随后的定量一致性，从而导致对白质变化的评估不足和临床意义较低的指标，无法诊断脑部疾病并研究潜在的疾病机制。我们在这里提出了一种综合的DTI采集方法，该方法解决了空间分辨率，空间保真度和运动敏感性的三个紧迫局限性，这阻碍了我们在发展中的大脑中的研究。此外，我们将在高分辨率DTI中应用新的采集方法来绘制脑瘫（CP）儿童的复杂大脑连通性，利用我们正在进行的努力，使用CP儿童的脐带血液（UCB）输注使用创新和有希望的干细胞疗法。我们预计我们的项目将提供强大的技术基础，以更好地表征CP中复杂电动途径的连通性障碍，并评估其在干细胞疗法期间的恢复。 DTI的空间可分胜性大大提高也将在翻译神经科学中更广泛的适用性。