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: 10187662
• 负责人: ALLEN W SONG
• 金额: $ 35.22万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187662
• 关键词: 3-Dimensional; Affect; Algorithms; Allogenic; Autologous; Behavioral; Birth; Blood Banks; Brain; Brain Diseases; Cell Therapy; Cells; Cerebral Palsy; Child; Childhood; Clinical; Cognitive; Collaborations; Computer software; Development; Diffusion Magnetic Resonance Imaging; Dose; Ensure; Foundations; Hematopoietic stem cells; Image; Immunity; Impaired cognition; Impairment; Individual; Injury; Innovative Therapy; Intervention; Investigation; Live Birth; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Methodology; Morphologic artifacts; Motion; Motor; Motor Pathways; Myelin; Noise; North Carolina; Pathology; Pathway interactions; Patients; Performance; Predisposition; Public Health; Recovery of Function; Research; Research Personnel; Resolution; Risk; Severities; Signal Transduction; Solid; System; Technology; The Sun; Time; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; base; brain repair; childhood motor disorders; clinical practice; connectome; disability; dosage; effective therapy; functional improvement; functional outcomes; image guided; improved; in utero; innovation; magnetic field; motor disorder; myelination; neuromechanism; next generation; novel; operation; perinatal injury; programs; radio frequency; reconstruction; repaired; restoration; stem cell therapy; stem cells; success; tool; white matter

Abstract: Cerebral palsy (CP) is the most prevalent motor disorder of childhood with complications in other cognitive impairments, affecting 3 out of every 1,000 children. Largely due to in utero or perinatal injuries to the developing brain, CP results in white matter pathology including impairments to the motor pathway. Diffusion MRI (e.g. diffusion tensor imaging, or DTI) can help characterize these white matter impairments, as well as any potential connectivity improvement during treatment. Over the past five years, we have applied high-fidelity diffusion MRI in pediatric CP patients during autologous umbilical cord blood (UCB) stem cell therapies, and developed an understanding of the impact and benefit autologous UCB stem cells have on improving functional outcome and brain connectivity in pediatric CP patients. Specifically, we have found strong evidences in relevant brain networks that: 1) brain connectivity impairments account for the motor and cognitive abnormalities in children with CP at the pre-treatment baseline, 2) brain connectivity increases have a direct impact on functional and behavioral improvements during UCB stem cell therapy, 3) brain connectivity increases beyond that of typical development trajectory have a direct correlation with stem cell dosage above a potential threshold of 1.98 x 107 cells/kg, and 4) the severity of baseline connectivity abnormalities predicts the risk of further decline and the benefit of cell therapy. It was also found that the brain connectivity increase may be associated with improved myelination during cell therapy, through additional preliminary investigations using quantitative susceptibility mapping (QSM). Advancing from this solid foundation, we propose this renewal application to further develop ultrahigh resolution diffusion MRI and connectivity imaging methodologies to study the positive effect of allogenic stem cells derived from UCB (stored at the North Carolina Cord Blood Bank), which can both reach the necessary high dosage (as opposed to the limited autologous UCB stem cells) and be applied to more CP patients (rather than just the ones with UCB saved at birth). Specifically, we propose to: 1) achieve unprecedented magnetic field homogeneity based on our recent innovation on simultaneous RF reception and Bo shimming technology to enable the highest possible spatial resolution and fidelity, 2) achieve multi-band multi-shot 3D diffusion MRI acquisition with ultrahigh submillimeter spatial resolution, optimized SNR and high throughput, and 3) acquire and analyze ultrahigh resolution diffusion MRI and brain connectome maps, as well as DTI-guided myelin-sensitive QSM along white matter pathways and throughout the brain connectome, in pediatric CP patients during the course of innovative therapies using UCB-derived allogenic stem cells. It is expected that our continued and concerted efforts will greatly advance our understanding of the neural mechanisms on both connectivity impairments in children with CP at the baseline and on the impact of stem cell therapy on connectivity restorations, ultimately providing compelling evidence to help plan the best treatment options.

抽象的： 脑瘫 (CP) 是儿童期最常见的运动障碍，并伴有其他认知障碍 每 1,000 名儿童中就有 3 名受到影响。很大程度上是由于子宫内或围产期损伤 发育中的大脑，CP 会导致白质病变，包括运动通路损伤。 扩散 MRI（例如扩散张量成像或 DTI）可以帮助表征这些白质损伤， 以及治疗期间任何潜在的连接改善。过去五年，我们申请了 小儿脑瘫患者自体脐带血 (UCB) 干细胞移植过程中的高保真扩散 MRI 疗法，并了解自体 UCB 干细胞对患者的影响和益处 改善儿科脑瘫患者的功能结果和大脑连接。具体来说，我们发现 相关大脑网络的有力证据表明：1）大脑连接障碍导致运动 CP 儿童在治疗前基线时出现认知异常，2) 大脑连接性增加 对 UCB 干细胞治疗期间的功能和行为改善有直接影响，3) 大脑 连接性的增加超出了典型的发育轨迹，与干细胞直接相关 剂量高于 1.98 x 107 个细胞/千克的潜在阈值，以及 4) 基线连接的严重程度 异常预示着进一步衰退的风险和细胞疗法的益处。还发现， 大脑连通性的增加可能与细胞治疗期间髓鞘形成的改善有关，通过 使用定量磁力图（QSM）进行额外的初步研究。从此出发 坚实的基础，我们提出这个更新应用，以进一步发展超高分辨率扩散磁共振成像 和连接成像方法来研究来自 UCB 的同种异体干细胞的积极作用 （储存在北卡罗来纳州脐带血库），两者都可以达到必要的高剂量（而不是 有限的自体 UCB 干细胞）并应用于更多的 CP 患者（而不仅仅是患有 CP 的患者） UCB 在出生时保存）。具体来说，我们建议：1）实现前所未有的基于磁场均匀性 关于我们最近在同步射频接收和 Bo 匀场技术方面的创新，以实现最高 可能的空间分辨率和保真度，2) 实现多波段多镜头 3D 扩散 MRI 采集 超高亚毫米空间分辨率、优化的信噪比和高吞吐量，以及 3) 采集和分析 超高分辨率扩散 MRI 和脑连接图，以及 DTI 引导的髓磷脂敏感 QSM 在儿科 CP 患者中，沿着白质通路和整个大脑连接组 使用UCB衍生的同种异体干细胞的创新疗法的过程。预计我们将继续并 共同努力将极大地增进我们对两种连接的神经机制的理解 脑瘫儿童基线损伤以及干细胞治疗对连通性的影响 修复，最终提供令人信服的证据来帮助规划最佳治疗方案。

项目成果

Column-based cortical depth analysis of the diffusion anisotropy and radiality in submillimeter whole-brain diffusion tensor imaging of the human cortical gray matter in vivo.

• DOI: 10.1016/j.neuroimage.2023.119993
• 发表时间: 2023-04-15
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Ma, Yixin;Bruce, Iain P.;Yeh, Chun-Hung;Petrella, Jeffrey R.;Song, Allen W.;Truong, Trong-Kha
• 通讯作者: Truong, Trong-Kha

Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial.

• DOI: 10.1002/sctm.17-0102
• 发表时间: 2017-12
• 期刊: Stem cells translational medicine
• 影响因子: 6
• 作者: Sun JM;Song AW;Case LE;Mikati MA;Gustafson KE;Simmons R;Goldstein R;Petry J;McLaughlin C;Waters-Pick B;Chen LW;Wease S;Blackwell B;Worley G;Troy J;Kurtzberg J
• 通讯作者: Kurtzberg J

Recent Advances in Radio-Frequency Coil Technologies: Flexible, Wireless, and Integrated Coil Arrays.

• DOI: 10.1002/jmri.27865
• 发表时间: 2022-04
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Darnell, Dean;Truong, Trong-Kha;Song, Allen W.
• 通讯作者: Song, Allen W.

Simultaneous and inherent correction of B0 and eddy-current induced distortions in high-resolution diffusion MRI using reversed polarity gradients and multiplexed sensitivity encoding (RPG-MUSE).

使用反向极性梯度和多路复用灵敏度编码 (RPG-MUSE) 对高分辨率扩散 MRI 中的 B0 和涡流引起的畸变进行同步和固有校正。

• DOI: 10.1016/j.neuroimage.2018.09.055
• 发表时间: 2018
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Bruce,IainP;Petty,Christopher;Song,AllenW
• 通讯作者: Song,AllenW