Novel Approaches for Magnetic Resonance Imaging of Neonatal Lung Structure and Function

磁共振成像（MRI）提供了安全、重复测量成人肺结构和功能区域变化的能力。将MRI扩展到儿童可以潜在地减少肺部疾病的终身负担，但尚未得到充分的探索。这在一定程度上是由于使用传统MRI技术从肺部获得的低MRI信号的图像质量较差。由于孩子的自然运动（例如：运动），这种情况会进一步减少。呼吸或血液流动)或自发的(例如：在执行扫描所需的相对较长的时间内，烦躁不安)。我的研究计划的总体目标是开发新的快速和强大的MRI方法来绘制儿童（从胎儿到青少年，包括婴儿）的肺结构和功能。该研究计划的短期目标是：(i)开发和测试新型加速质子MRI图像采集硬件和软件，以提高新生儿肺部MRI的速度和质量；（ii）优化和验证自由呼吸MRI方法，以捕获和量化与呼吸相关的MRI信号变化。（iii）开发新的吸入惰性气体MRI方法，以便简单安全地绘制通风图。这些肺部MRI方法将在动物和儿童（包括通气新生儿）中进行测试。这些目标将由几名学员（1名博士后、1名博士生和2名硕士生）完成，他们将利用多伦多大学医学物理和生物物理培训项目的多学科研究和研究生培训环境，以及病童医院的核磁共振、儿科放射学、重症监护、呼吸学和新生儿学环境。*******本提案中所描述的新生儿肺部MRI方法的发展将为基础和应用知识的产生提供重要的机会。这些工具将使新的机制洞察和假设检验相关的健康肺生理和病理生理在新生儿，以及跟踪疾病进展和对治疗的反应以前是不可能的。具体来说，该研究将使MRI首次用于检测和跟踪早产儿肺部疾病的解剖和功能后果。在儿童健康研究环境中进行这些先进的MRI技术的能力是一个前所未有的机会，将加拿大成像科学家定位在儿科研究这一重要领域的前沿。由于许多临床MRI平台将能够采用该研究计划开发的硬件和软件工具，因此将这些知识转化为学术和医疗保健机构的研究人员的途径是强大的，这为生物医学领域的培训和商业化提供了额外的机会。******

Magnetic Resonance Imaging (MRI) provides the ability to safely and repeatedly measure regional changes in lung structure and function in adults. The extension of MRI to children can potentially reduce the life-long burden of lung disease but has not yet been fully explored. This is in part due to poor image quality from the low MRI signals available from the lung using conventional MRI technology. This is further diminished by motion of the child, either natural (eg. breathing or blood flow) or spontaneous (eg. restlessness), during the relatively long time required to perform a scan. The overall objective of my research program is to develop new rapid and robust MRI methods for mapping of lung structure and function in children (from fetus through to adolescent, including infants). The short-term objectives of the proposed research program are: (i) to develop and test novel accelerated proton MRI image acquisition hardware and software to improve the speed and quality of neonatal lung MRI, (ii) to optimize and validate free-breathing MRI approaches to capture and quantify MRI signal changes associated with breathing (ie. ventilation) and blood flow and (iii) to develop new inhaled inert gas MRI approaches to simply and safely enable mapping of ventilation. These lung MRI methods will be tested in both animals and children, including ventilated neonates. These objectives will be accomplished by several trainees (1 post-doctoral fellow, 1 PhD student and 2 MSc students), leveraging the multidisciplinary research and graduate training environment within the medical physics and biophysics training program at the University of Toronto and the MRI, pediatric radiology, critical care, respirology and neonatology environment at the Hospital for Sick Children.*******The development of neonatal lung MRI approaches as described in this proposal will provide significant opportunities for knowledge generation, both basic and applied. These tools will enable new mechanistic insight and hypothesis testing related to healthy lung physiology and pathophysiology in neonates as well as tracking of disease progression and response to therapy not previously possible. Specifically, the proposed research will enable MRI to be used to detect and follow both the anatomical and functional consequences of lung disease of prematurity for the first time. The ability to conduct these advanced MRI techniques in a children's health research setting is an unprecedented opportunity to position Canadian imaging scientists at the forefront of this important area of pediatric research. The pathway for translation of this knowledge to researchers in the academic and health-care settings is strong since many clinical MRI platforms will be able to adopt the hardware and software tools developed by this research program, providing additional opportunity for training and commercialization within the biomedical sector.******