High-Speed Motion-Corrected Pediatric Neuroimaging with MRI

描述(由申请人提供)：拟议的工作旨在通过开发和临床评估新的MRI脉冲序列，提高在没有镇静和麻醉的情况下获得的儿童和胎儿神经成像MRI数据的质量。镇静和麻醉占儿童神经成像MRI研究费用的很大比例，并增加了患者的风险和扫描所需的时间。虽然一些临床神经成像研究在没有镇静的情况下进行了尝试，但成功并不一致，由此产生的图像质量通常被认为是边缘的。在研究环境中，MRI经常不能用于研究儿童，因为镇静的风险在伦理上是不合理的；这限制了MRI在研究发育和儿科疾病方面的使用。在胎儿MRI中，运动会导致数据退化和扫描时间延长。该提案的研究目标提供了一系列开发和测试阶段，旨在产生高速运动校正的MRI脉冲序列来解决这些问题。创建建议序列的第一步是在选择的临床MRI序列中添加体积导航仪，这些序列已经过量身定制，以从现代高通道计数线圈阵列中获得最大的时间节约。嵌入在这些序列中的导航器将用于跟踪扫描过程中受试者头部的运动，并实时自动更新扫描仪的成像坐标。此外，检测到因被摄体运动而退化的扫描部分将被自动重新采集。该项目的第二阶段包括开发新颖的高速图像配准软件，该软件将提高运动跟踪的精度。这些第一阶段的开发工作将主要在阿蒂努拉·A·马蒂诺斯生物医学成像中心进行，利用其工程资源、7台大口径核磁共振扫描仪以及在核磁共振物理、脉冲序列编程和医学图像分析算法方面的大量合作人员。在开发阶段，将在波士顿儿童医院(BCH)的临床MRI系统上与儿科志愿者一起进行额外的试点测试。作为第三阶段，当序列开发完成后，我们建议使用BCH的临床试验来验证这些工具，目的是证明在没有镇静的情况下扫描的儿科受试者在质量和效率方面的改进。这项临床试验将利用放射科的儿童生活、护理、放射学技术、放射科医生和研究支持人员，以及BCH的胎儿新生儿神经成像和发育科学中心。该项目还将继续进行一项试点研究，通过开发特定于胎儿的高速运动校正序列，将这项技术应用于胎儿神经成像--这一群体的独特之处在于，竞争对手基于光学和探头的运动校正系统无法应用，这使得使用导航序列特别有吸引力。总之，这些步骤将推进候选人的长期职业目标，即成为一名独立研究人员，专注于开发新的核磁共振技术，并将进展转化为临床和神经科学研究实践。在此期间的开发工作将有助于巩固Tisdall博士在脉冲序列编程和核磁共振物理方面的知识。这也将使他有机会在配准和分割等医学图像分析技术方面进行更深入的研究。这些技术技能将对他未来的研究生涯目标有所帮助。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，该提案的临床试验部分将提供对这些内容的宝贵接触 任务，同时与更资深的研究人员合作。最后，这项研究收集的结果将有助于指导蒂斯德尔博士未来的工作，为解决临床影像问题提出新的理论进展。除了该提案的重要研究部分外，Tisdall博士还将在最初的两年指导职业发展阶段，将25%的时间用于选定的任务，以帮助他成为医学成像领域的一名成功的独立研究人员。在此期间，Tisdall博士将在哈佛医学院和麻省理工学院参加神经解剖学和疾病以及临床试验设计方面的课程，并在马萨诸塞州综合医院和BCH参加职业发展研讨会。他还将在波士顿儿童医院进行为期4周的临床体验，在那里他将跟踪Ellen Grant医生，并观察MRI扫描过程和图像读取。这些直接培训部分旨在拓宽Tisdall博士在临床和研究神经成像实践、临床护理的提供以及临床研究的开发和管理方面的知识。Tisdall博士还将通过每周与Bruce Fischl博士和Andr‘van der Kouwe博士会面，以及每月与Martinos中心的Lawrence Wald博士会面，获得关于研究、学术和职业发展主题的定期指导和反馈。他还将在BCH与Ellen Grant博士每两周举行一次会议。每六个月，Fischl博士和Grant博士都会评估Tisdall博士的研究和职业发展进展，并与他会面提供反馈。通过这两年的指导开发，蒂斯德尔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.