High-Speed Motion-Corrected Pediatric Neuroimaging with MRI

描述（由申请人提供）：拟定工作旨在通过开发和临床评价新型MRI脉冲序列，提高在无镇静和麻醉的情况下采集的儿科和胎儿神经成像MRI数据的质量。镇静和麻醉在儿科神经影像MRI研究的成本中占很大比例，并且增加了患者的风险和扫描所需的时间。尽管一些临床神经影像学研究尝试不使用镇静剂，但成功并不一致，并且所得图像质量通常被认为是边缘的。在研究环境中，MRI通常不适用于研究儿童，因为镇静的风险在伦理上是不合理的;这限制了MRI用于研究发育和儿科疾病。在胎儿MRI中，运动会导致数据降级和扫描时间延长。本提案的研究目的是提供一系列开发和测试阶段，旨在产生高速运动校正MRI脉冲序列，以解决这些问题。创建建议序列的第一步是将体积导航器添加到临床MRI序列的选择中，这些序列经过定制，可从现代高通道数线圈阵列中获得最大的时间节省。这些序列中嵌入的导航器将用于跟踪扫描过程中受试者头部的运动，并真实的实时自动更新扫描仪的成像坐标。此外，将自动重新获取被检测到因受试者运动而降级的扫描部分。该项目的第二阶段包括开发新的高速图像配准软件，以提高运动跟踪的准确性。这些开发工作的第一阶段将主要在Athinoula A进行。Martinos生物医学成像中心，利用其工程资源，7大口径MRI扫描仪，以及MRI物理，脉冲序列编程和医学图像分析算法的大量合作者。在开发阶段，将在波士顿儿童医院（BCH）的临床MRI系统上对儿科志愿者进行额外的初步测试。作为第三阶段，当序列开发完成时，我们建议使用BCH的临床试验来验证这些工具，目的是证明在无镇静扫描的儿科受试者中质量和效率的提高。这项临床试验将利用儿童生活，护理，放射技术，放射科医生和放射科研究支持人员以及BCH的胎儿新生儿神经成像和发育科学中心。该项目还将进行一项试点研究，通过开发胎儿特定的高速运动校正序列将该技术应用于胎儿神经成像-该人群是独特的，因为竞争的光学和基于探针的运动校正系统无法应用，使得导航序列的使用特别有吸引力。这些步骤将共同推进候选人的长期职业目标，即成为一名专注于开发新型MRI技术并将进展转化为临床和神经科学研究实践的独立研究人员。在此期间的开发工作将有助于巩固Tisdall博士的脉冲序列编程和MRI物理知识。这也将使他有机会更深入地研究医学图像分析技术，如配准和分割。这些技术技能将有助于他未来的研究事业目标。此外，设计和实施临床试验研究的过程对于Tisdall博士开发具有直接临床影响的技术的未来目标至关重要。因此，本提案的临床试验部分将提供宝贵的接触这些 与更资深的研究人员合作。最后，从研究中收集的结果将有助于指导Tisdall博士未来的工作，提出解决临床成像问题的新理论进展。除了该提案的重要研究部分外，还有一个为期两年的初始指导职业发展阶段，Tisdall博士将花费25%的时间完成选定的任务，以帮助他成为医学成像领域成功的独立研究人员。作为这一时期的一部分，Tisdall博士将参加哈佛医学院和麻省理工学院的神经解剖学和疾病以及临床试验设计课程，并参加马萨诸塞州总医院和BCH的职业发展研讨会。他还将在波士顿儿童医院进行为期4周的临床体验，在那里他将跟随埃伦·格兰特博士，观察MRI扫描和图像阅读。这些直接培训内容旨在拓宽Tisdall博士在临床和研究神经影像学实践、临床护理提供以及临床研究开发和管理方面的知识。Tisdall博士还将通过与布鲁斯菲舍尔博士和安德烈货车德库韦博士的每周会议，以及与马蒂诺斯中心的劳伦斯沃尔德博士的每月会议，定期接受有关研究、学术和职业发展主题的指导和反馈。他还将在BCH与艾伦·格兰特博士每两周举行一次会议。每六个月，Fischl博士和Grant博士将评估Tisdall博士的研究和职业发展进展，并与他会面提供反馈。通过这两年的指导发展，Tisdall博士将磨练他的技术技能，并大幅发展他的临床和研究设计知识，为他向独立的过渡做好准备。

DESCRIPTION (provided by applicant): The proposed work aims to improve the quality of pediatric and fetal neuroimaging MRI data acquired without sedation and anesthesia through the development and clinical evaluation of novel MRI pulse sequences. Sedation and anesthesia account for a significant percentage of the cost of pediatric neuroimaging MRI studies, and increase both the risk to the patient and the time required for a scan. Although some clinical neuroimaging studies are attempted without sedation, success is not consistent and the resulting image quality is often considered marginal. In the research setting, MRI is frequently not available to study children because the risks of sedation are not ethically justifiable; this limits the use of MRI for studying development and pediatric disease. In fetal MRI, motion results in degraded data and longer scan sessions. The research aims of this proposal provide a sequence of development and testing stages designed to produce high-speed motion-corrected MRI pulse sequences to address these issues. The first step in creating the proposed sequences is the addition of volumetric navigators to a selection of clinical MRI sequences that have been tailored to gain the maximum savings in time from modern high- channel-count coil arrays. The navigators embedded in these sequences will be used to track the motion of the subject's head during scanning and automatically update the scanner's imaging coordinates in real time. Additionally, portions of the scan that are detected to be degraded by subject motion will be automatically reacquired. The second stage of the project consists of developing novel high-speed image registration software that will improve the accuracy of the motion tracking. These first stages of development work will take place mostly at the Athinoula A. Martinos Center for Biomedical imaging, taking advantage of its engineering resources, 7 large-bore MRI scanners, and the large pool of collaborators in MRI physics, pulse sequence programming, and medical image analysis algorithms. Additional pilot testing during the development phase will be performed with pediatric volunteers on the clinical MRI systems at Boston Children's Hospital (BCH). As a third stage, when the sequence development is complete, we propose to validate the tools using a clinical trial at BCH, with the goal of demonstrating improvements in quality and efficiency in pediatric subjects scanned without sedation. This clinical trail will take advantage of the child life, nursing, radiology technologis, radiologist, and research support staff in Radiology and the Fetal Neonatal Neuroimaging & Developmental Science Center at BCH. The project will also proceed to a pilot study applying this technology to fetal neuroimaging via the development of a fetal-specific high-speed motion-corrected sequence - this population is unique in that competing optical- and probe-based motion-correction systems cannot be applied, making the use of navigated sequences particularly attractive. Together, these steps will advance the candidate's long-term career goal of becoming an independent researcher focused on developing novel MRI technology and translating advances into clinical and neuroscience research practice. The development work during this period will help solidify Dr. Tisdall's knowledge of pulse sequence programming and MRI physics. It will also give him the opportunity to study more deeply in medical image analysis techniques such as registration and segmentation. These technical skills will be of use to his future research career goals. Additionally, the process of designing and implementing a clinical trial study will be essential to Dr. Tisdall's future goal of developing technology with direct cliical impact. Thus, the clinical trial portion of this proposal will provide invaluable exposure to these tasks while collaborating with more senior researchers. Finally, the results gathered from the study will help direct future work by Dr. Tisdall, suggesting new theoretical advances to address clinical imaging issues. In addition to the significant research component of the proposal, there is also an initial two-year mentored career development phase in which Dr. Tisdall will spend a 25% of his time on tasks selected to help him become a successful independent researcher in medical imaging. As part of this period, Dr. Tisdall will attend courses in neuroanatomy and disease, and clinical trial design at Harvard Medical School and MIT, and participate in career development seminars at Massachusetts General Hospital and BCH. He will also have a 4-week clinical experience period at Children's Hospital Boston, where he will shadow Dr. Ellen Grant and observe both MRI scanning sessions and image reading. Together these direct training components are designed to broaden Dr. Tisdall's knowledge of clinical and research neuroimaging practices, the delivery of clinical care, and the development and management of clinical research. Dr. Tisdall will also receive regular mentorship and feedback on research, academic, and career development topics via weekly meetings with Drs. Bruce Fischl and Andr� van der Kouwe, and monthly meetings with Dr. Lawrence Wald at the Martinos Center. He will also have biweekly meetings with Dr. Ellen Grant at BCH. Every six months Drs. Fischl and Grant will evaluate Dr. Tisdall's research and career development progress, and meet with him to provide feedback. Through these two years of mentored development, Dr. Tisdall will hone his technical skills, and substantially develop his clinical and study-design knowledge, preparing his transition to independence.