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）：最近出现的扩散张量成像（DTI）通过水扩散特性提供了一种新的对比机制，以研究人脑白质的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 最有价值和最合适的应用之一是研究儿童发育中的大脑，因为儿童中的许多衰弱疾病都源于白质异常和损伤。例如，脑瘫 (CP) 是由子宫内或围产期运动通路损伤引起的，是儿童期最常见的运动障碍，每 1,000 名活产儿中就有 2 至 3 人受到影响。其明确的白质病理学将受益于 DTI 提供的独特白质表征。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治疗期间的恢复。造成这种不足的因素有很多，其中最主要的是实现高空间分辨率的技术限制、DTI 脉冲序列固有的系统失真（会在张量估计中引入失真和误差）以及由于到大的扩散权重梯度，这进一步使患者群体的实际应用变得复杂。这些缺点尤其在儿童等弱势群体中更加严重。在本提案中，我们的目标是通过开发创新的采集解决方案来解决当前的这些限制，以实现急需的空间分辨率和保真度，并随后应用我们的创新 DTI 采集方法，利用我们强大的合作伙伴关系，更好地表征 CP 儿童的大脑连接拥有长期成功的临床计划，通过脐带血（UCB）输注使用创新且有前景的干细胞疗法。具体来说，我们建议：1）实现更好地描绘复杂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估计和与神经解剖学的共同配准，3）实现大大降低的运动灵敏度以提高实用性在儿科患者群体中，4) 获取并开发 CP 中的儿科大脑连接图，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。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能力 DTI 测量的一致性，可以提高我们对干细胞治疗前景的认识，并有助于为 CP 儿童设计最佳治疗方案。我们的新方法也有可能在基础和临床神经科学领域得到更广泛的应用。 公共健康相关性：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研究白质微观结构、发育和病理学的新维度。然而，所得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，导致对白质变化的评估不充分，以及诊断大脑疾病和研究潜在疾病机制的临床意义较小的指标。我们在这里提出了一种集成的 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方面的三个紧迫限制，这些限制阻碍了我们对发育中大脑的研究。此外，我们将利用高分辨率 DTI 中的新采集方法来绘制脑瘫 (CP) 儿童复杂的大脑连接图，利用我们通过脐带血 (UCB) 进行创新且有前景的干细胞疗法的持续努力CP 儿童输注。我们预计我们的项目将提供坚实的技术基础，以更好地表征脑瘫复杂运动通路中的连接障碍，并评估其在干细胞治疗期间的恢复情况。 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应用。