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.
We propose to improve the quality of pediatric and fetal neuroimaging MRI data acquired without sedation and anesthesia. This will enable a reduction in the need for sedation and, in turn, the cost and risk of these studies and increase availability of MRI for fetal and pediatric imaging. This goal will be achieved using novel technology involving new sequences that are time-efficient and motion-resistant through the use of parallel acceleration, prospective motion-correction, and automatic data reacquisition.
