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

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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.