My work in the Department of Neurology at Children's Hospital Boston comprises research, patient care, and resident/medical student education. My research addresses questions of brain and cognitive development in children. Initially, I concentrated upon development of a human fetal glial cell culture system to study the effects of growth factors upon human oligodendrocyte development. Subsequent work led to description of the steps in oligodendrocyte development in fetal human brain tissue culture and slices. Next, I focused on cell cycle mechanisms that govern neuronal proliferation in cerebral cortex, specifically a key regulator of the cyclin-cyclin dependent kinase complex, p27kip1. Work with a p27kip1 knockout mouse revealed that p27kip1 serves as an important determinant of the final number of neurons produced in the murine brain during prenatal development.
Due to the development of quantitative imaging tools permitting in vivo and non-invasive study of brain and cognitive/behavioral development in children, I shifted my investigative toolset to neuroimaging. Currently, we use advanced MRI techniques such as functional magnetic resonance imaging (fMRI), volumetric imaging, and diffusion tensor imaging for non-invasive investigation of the developing brain in children. One line of research in the lab has addressed the development of mnemonic capability in childhood. We have conducted developmental studies using fMRI designed to compare verbal memory encoding in children and adults. This has led to the identification of neural activation patterns that differentiate children below the age of 13 years from adults who demonstrate equivalent behavioral performance on the mnemonic task. A second line of research has employed quantitative volumetric MR imaging to investigate the hypothesis that long-term evidence can be found in the adolescent brain of prenatal drug exposure to cocaine, alcohol, cigarettes or marijuana. We found that reductions in gray matter volume and total brain volume are associated with individual exposures to cocaine, cigarettes and alcohol. Moreover, a strong inverse relationship exists between total- and cortical gray matter volumes and the number of types of prenatal exposures. Third, we have studied teenagers surgically treated for transposition of the great arteries (TGA) or Tetralogy of Fallot (TOF) as infants with quantitative volumetric MR imaging, fMRI and diffusion tensor imaging (DTI). This NIH funded work in which we collaborated with the Department of Cardiology at Children’s Hospital Boston has revealed significantly reduced cortical and subcortical volumes of tissue among children with TOF or TGA as compared to controls at the age of 15 years. In addition, both the TOF and TGA groups have demonstrated deficits as adolescents in executive and visual-spatial processing on cognitive testing that were first evident earlier in childhood. Using fMRI and diffusion tensor imaging methods, we have found differences in neural activation and white matter microstructure among adolescent control, TOF and TGA children. We are in the midst of reporting these results. Currently, we are actively engaged in the data analysis phase of our NIH funded project, Brain Structure and Function in Adolescents after the Fontan Operation (RO1 HL096825, Newburger and Rivkin, Co-PIs).
We served as one of the seven Pediatric Study Centers in the NIH Study of Normal Brain Development to generate the first analyzed normative, correlated neurobehavioral-neuroimaging database for children. We completed data acquisition for this landmark project having assembled data from over 300 sessions with children at each of which MRI, neurobehavioral and neurologic data were collected. Finally, we are significantly involved in three multicenter studies in pediatric stroke. In the first, we are active participants in the International Pediatric Stroke Study which recruits pediatric patients with stroke, extracts their clinical data and submits it to an international registry for the purpose of clinical research on this group of disorders. Second, our center participated in the NIH funded multicenter study, the Vascular Effects of Infection in Pediatric Stroke and we are active participants in work to gain NIH support for its follow-up proposal. Third, my lab served as the Imaging Core in the recently NIH funded and multicenter trial, Thrombolysis in Pediatric Stroke (in which we will also participated as a recruiting center). Once again our research group will serve as the Imaging Core for the multicenter NIH proposal to study tPA treatment of childrn with stroke
My clinical activity continues to include out-patient care of children with stroke and other cerebrovascular disorders that fills one and one half days each week. In addition, I have served as the attending physician on the In-Patient General Neurology, Intensive Care Neurology, and Neurologist of the Week services for 8-10 weeks per year. The focus of my clinical activity fixes upon children with cerebrovascular disorders and stroke. I organize and direct the first dedicated Cerebrovascular Disorders and Stroke service at Boston Children’s Hospital. This multidisciplinary service provides clinical care to these important patients; it provides in-patient care to affected patients on the Neurology In-patient Service, consultation to patients who may have suffered stroke on other in-patient services, and follow-up care for all in-patients diagnosed with stroke at Children’s Hospital Boston. We expect to study this patient group extensively with multi-modal MR neuroimaging for the purpose of elucidating aspects of adaptive neuroplasticity and improved care of children with this disorder. Finally, we initiated a clinical fMRI service that provides clinical studies for evaluation of eloquent cortex in children who are surgical candidates for treatment of epilepsy or brain malformation. The resulting fMRI activation maps are used for surgical planning. These clinical studies yield data that are analyzed for both clinical and research purposes.
In the administrative/education domain, I serve as the Intensive Care Neurology Service director for the Department of Neurology at Boston Children's Hospital. In this role since 2012, I have dealt with matters of neurologic care of patients in the 6 intensive care units covered by our program. The position provides frequent interaction with the leadership and staff of the neonatal-, cardiac- and medical-surgical intensive care units we serve. We continue to develop protocols for specific disorders so that standardized neurocritical care can be provided to patients and the resulting clinical data can be utilized for improvement of care delivered. I serve on two principal hospital committees. I continue to serve as a member of the Executive Board of the Department of Neurology. In addition, I co-chair the hospital’s Pharmacy and Therapeutics Committee; this committee oversees all matters related to pharmacologic and medical treatment of patients at Boston Children’s Hospital.
Resident and medical student education constitute the majority of my teaching effort. I teach in the Residents Core Curriculum in the Department of Neurology. This weekly lecture series in pediatric neurology comprises the didactic core for our pediatric neurology trainees. I teach units on neuroimaging, neuro-metabolic disorders, and stroke and cerebrovascular diseases in childhood. In addition, as attending physician on the Neurology In-patient and Critical Care Neurology services, I provide instruction to pediatrics residents, adult and pediatric neurology residents, and medical students daily during the several weeks I serve in this capacity each year. I have also participated in our department's resident advisor program. In this capacity, I have provided counsel to trainees as they have plied their respective 3 year courses of training.