Imaging Neonatal Hypoxic Ischemic Injury

Abstract Hypoxic ischemic (HI) insult damages both white matter and grey matter in infants and causes significant mortality and morbidity. To investigate the pathological mechanisms of neonatal HI injury and find satisfactory treatments, animal models of neonatal HI injury have been established and widely used. In this project, novel in vivo magnetic resonance imaging techniques that target tissue microstructure and water exchange between intra- and extra-cellular spaces will be developed to examine the progression of HI injury and the effects of therapeutic hypothermia in a neonatal mouse model. In aim 1, we will develop diffusion MRI (dMRI) based techniques to measure microstructural changes and water exchange and validated the techniques using histology. We will use these techniques to characterize the extent and severity of cell death and to predict tissue survival in edema regions. In aim 2, we will further validate the dMRI techniques developed in aim 1 using maps of metabolites and lipids generated using mass spectrometry imaging. In aim 3, the techniques developed in the first two aims will be applied to characterize HI injury in mice treated with hypothermia to study its effects and elucidate its neuroprotective mechanisms. We expect the project to extend our knowledge on the relationships between HI pathology and diagnostic markers in this mouse model and shed light on the mechanisms of HI injury and therapeutic hypothermia. This information and techniques developed in this project will be useful to design effective strategies for intervention and to monitor treatment response in studies using this or similar models.