Investigation of Cerebral Hemodynamics and Oxygenation Relationships Under Sedation in Children: ICHOR USC

Project Summary
The broad objective of this research is to use neuroimaging to understand the hemodynamic responses
to anesthesia and sedation. Anesthesia and sedation, commonly used in pediatric patients, cause
profound and rapid changes in cerebral blood flow and metabolism. Under normal conditions in
adults, these changes are tightly coupled to one another to protect the brain from hypoxia and
ischemia. However, the extent to which flow and metabolism are coupled during anesthesia and
sedation in pediatric patients is unknown. The aims of this project are (1) to quantify the
hemodynamic and metabolic responses to anesthesia in infants, and (2) to compare those responses
during the administration of specific anesthetics in infants with differing disease states that may
make them more vulnerable to the uncoupling of flow from metabolism. If our hypotheses are borne
out and infants are particularly vulnerable to this uncoupling, our findings will lead to future
studies to assess hemodynamic responses as potential biomarkers that predict and mediate adverse
outcomes in infants exposed to anesthesia. Therefore, this project is relevant to the NHLBI's
strategic objective to identify factors that account for individual differences in pathobiology and
treatment response.
This project requires an opportunity for making simultaneous flow and metabolism measurements in
anesthetized infants. Clinical MR imaging provides this opportunity. Therefore, we will enroll into
a Naturalistic Cohort Study 120 infants younger than 1 year of age who require a clinical MRI scan,
half receiving anesthesia and half not. Enrolled infants will be imaged with MRI sequences that
measure cerebral blood flow and metabolism. In addition, we will enroll 30 additional infants of
the same age into a Pilot Randomized Comparator Trial (RCT), in which the infants will be
randomized to receive either propofol or sevoflurane anesthesia. Randomization will dramatically
reduce potential confounding of diseases and anesthetic agents present in the naturalistic study.
Learning to design RCTs (Goal 1) is addressed with didactics and a practicum to advance my
translational research skills. This project requires my learning how anesthetics and sedatives
alter hemodynamics and fluid dynamics (Goal 2) and how the known and putative mechanisms of
neurotoxicity and flow-metabolism uncoupling affect the developing brain (Goal 3). This project and
my research career will help infants who require anesthesia or sedation. It creates a paradigm in
which the hemodynamic response to anesthesia can be explored safely in pediatric critical care
patients. It requires the combination of MRI and image processing know-how - skills that I already
have - with a deeper understanding of the pathophysiological consequences of altered hemodynamic
responses to anesthesia in infants. It also requires that I develop an improved ability to design
research projects that fit within a rigorous and narrow clinical opportunity - skills that I will
gain with this K25 support.

Grant Number: 5K25HL153954-05
NIH Institute/Center: NIH
Principal Investigator: Matthew Borzage