The overall goal of this application is to assess the feasibility of a noninvasive approach to patient-specific determination and monitoring of intracranial pressure (ICP) in a pediatric patient population. The proposed research is an important first step towards making this cardinal 'cranial vital sign'available in a much broader pediatric patient population than is currently possible. The PI is an expert in biomedical engineering, especially the modeling and identification of physiological systems, with highly relevant prior research experience. He has assembled a first-class team consisting of Dr. Robert Tasker, Chair of Neurocritical Care, Dr. Shenandoah Robinson, pediatric neurosurgeon, and Dr. Kush Kapur, Senior Biostatistician, all at Boston Children's Hospital (BCH). The combined resources available at the Computational Physiology &Clinical Inference Group at the Massachusetts Institute of Technology and the Departments of Neurology, Anesthesiology, and Neurosurgery at BCH ensure optimal support for this research project. ICP is important to track in a variety of conditions affecting the brain. Its measurement, however, requires surgical penetration of the skull and placement of a pressure-sensitive probe in the brain parenchyma, or insertion of a catheter into the ventricular or extra- ventricular cerebrospinal fluid spaces. This invasiveness and the associated risks cause ICP measurements in current clinical practice to only be made in a small subset of patients whose diagnosis and treatment could benefit from knowing ICP. The gap is particularly apparent for pediatric patients, in whom TBI is the leading cause of death and disability, but where the threshold for invasive ICP monitoring is severe injury and coma, defined as Glasgow Coma Scale score less than 9. Consequently, ICP measurements are limited to specialized care facilities and are performed in only those patients for whom the risks of the procedures are outweighed by the overriding need to know ICP for diagnostic or therapeutic purposes. To support the development of a robust, accurate, and precise method for determining ICP entirely noninvasively in children, we will collect (and make available to the research community) ICP and noninvasive arterial blood pressure (nABP) and cerebral blood flow velocity (CBFV) waveform signals in pediatric patients undergoing invasive ICP measurements (Aim 1) for treatment of severe traumatic brain injury and placement of cerebral shunts for hydrocephalus. We will also adapt a previously developed approach to minimally invasive ICP determination in adults to the characteristics of the nABP and CBFV signals and the cerebrovascular dynamics in pediatric patients. Success with these aims will allow us to quantify the preliminary performance of an entirely noninvasive approach to continuous determination of absolute ICP in children and young adolescents, which will enable us to design prospective, multicenter validation studies. A prospectively validated approach to noninvasive determination of absolute ICP would significantly improve neurologic, neurosurgical, and neurocritical care in children.

Public Health Relevance

While intracranial pressure is an important physiologic variable to determine in children with traumatic brain injury and hydrocephalus, its measurement is very invasive, hence limiting access to this key 'cerebral vital sign.'Here, we assess the feasibility of patient-specific, continuous, and noninvasive determination of absolute intracranial pressure in pediatric patients. The results of this research will enable prospective, multicenter validation of noninvasive intracranial pressure determination in children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS084264-01A1
Application #
8702340
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Bellgowan, Patrick S F
Project Start
2014-07-15
Project End
2016-03-31
Budget Start
2014-07-15
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02142