Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

Arjun G. Yodh

Second Advisor

Daniel J. Licht

Abstract

Adequate oxygen and blood flow are vital for the developing pediatric brain. Herein, we apply quantitative diffuse optical techniques, frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), to non-invasively characterize cerebral oxygenation (StO2), blood flow (CBF), and oxygen metabolism (CMRO2) in pediatric animal models of hypoxic-ischemic injury.

In a neonatal swine model (n=8) of congenital cardiac defect repair, we performed a two-part study which validated non-invasive diffuse optical measurements and uncovered significant limitations in the guidance of deep hypothermia using temperature during cardiopulmonary bypass. First, non-invasive CMRO2 was validated against invasive methods over wide temperature ranges (18-37C). Non-invasive measurements of CBF (p<0.001) and CMRO2 (p<0.001) were significantly associated with invasive measurements. Furthermore, a significant hysteresis (p=0.001) of cerebral metabolic temperature-dependence during cooling versus rewarming with respect to NPT is “fixed” with the use of ICT (p>0.5).

Second, we compared non-invasively measured cerebral metabolic parameters between cohorts who underwent deep hypothermia with or without circulatory arrest (DHCA; n=8). Cerebral metabolic temperature-dependence with respect to ICT in DHCA animals demonstrated significantly diminished temperature sensitivity during rewarming (p<0.001; i.e., following reperfusion) compared to during cooling. Direct non-invasive CMRO2 measurement is an improved surrogate of cerebral status over temperature and enables individualized management of deep hypothermia and circulatory arrest.

In another study of asphyxia-induced pediatric cardiac arrest and cardiopulmonary resuscitation (CPR), non-invasive measures of StO2, oxy-hemoglobin concentration ([HbO2]) and total hemoglobin concentration (THC) at 10-minutes of CPR were significantly associated with return of spontaneous circulation (ROSC). The absolute change in [HbO2] from 1-minute of CPR ([HbO2]CPR) was the optimal predictor of ROSC, with a mean (SD) AUC of 0.91 (0.07) across the first 10 minutes of CPR, evaluated at 1-minute intervals. Furthermore, separate high sensitivity and specificity threshold for ROSC were established.

These results show, in several contexts, that non-invasive FD-DOS/DCS neuromonitoring provides unique physiological information about the developing pediatric brain that enables individualized identification of critical neurological risk periods and real-time guidance of clinical care.

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