DESCRIPTION (provided by applicant): My goal is to become a uniquely qualified, highly productive, independent biomedical investigator of abusive head trauma (AHT) in children. Specifically, I am interested in studying lesion evolution in children and modeling this type of injury in piglets to develop age- and injury-specific treatments that will translate to effective therapies for infants and children. Successful interventions to lessen the burden of morbidity and mortality after injury require understanding the pathophysiological cascades that lead to the extensive injury patterns observed. Currently, the pathophysiology of AHT in children is poorly understood, though clues exist from clinical, radiologic, biomechanical, and pathologic observations. I will initially focus on investigating the age-dependent pathophysiology after injuries and insults characteristic of AHT in our unique immature large- animal model. Though I have considerable basic neuroscience experience and have studied accidental pediatric head trauma in Dr. Duhaime's translational lab, it has only been through recent increasing clinical exposure that I have become aware of this pervasive and understudied public health problem that garners more controversy than data and answers. In order to accurately model AHT in my future independent career, I request additional multidisciplinary training in clinical abusive head trauma through coursework at Harvard Medical School, national and international meetings, a forensic pathology observership, and training by Drs. Duhaime, Newton, and McGuone who are clinicians treating and studying children with AHT. Focused training in what is known about this injury (clinical presentation, injury evolution, and outcome metrics via MRI or autopsy) will allow me to more accurately model, characterize, and interpret this complex injury in our piglets and to translate this to the pathophysiology in children. As one important component, subclinical and clinical seizures are common after AHT and are highly likely to contribute to the pathophysiological cascades due to unique features of the developing brain. In order to study the potential role of seizures in exacerbating damage after AHT, I request training from Dr. Staley who is a world leader in electrographic seizure detection, ion transport, and basic pathophysiology of cytotoxic cerebral edema in the immature brain. I will gain additional in- depth knowledge of developmental differences in the immature brain through coursework at Harvard University. In vivo imaging is a powerful tool to study injured children and observe the parallel injury in our model. Therefore, I seek training through coursework at MIT and the Martinos Center for Bioimaging and with Dr. Hunter who is a world authority in the use of MRI to study head injury in children. With my previous experience in the field of accidental pediatric brain trauma, my team of mentors and collaborators, and the educational opportunities at MGH/ ...