Functional Diffuse Optical Measurements of Psychomotor Function in Neonates with Hypoplastic Left Heart Syndrome (HLHS)

University Of Pennsylvania, Philadelphia PA

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Abstract

Non-invasive, functional neuroimaging is needed to assess the role of psychomotor function in feeding dysfunction present in over 50% of neonates with hypoplastic left heart syndrome (HLHS) at discharge1. While feeding dysfunction often causes immediate and debilitating consequences in growth and quality-of-life, the lack of quantitative tools to discern whether potential underlying neurologic deficits are psychomotor, reflexive, or more peripheral in origin prevents targeted management before compounding long-term effects manifest at school age. Non-invasive techniques of near-infrared diffuse optical spectroscopy (NIRS/DOS) for cerebral tissue oxygenation (StO2) and diffuse correlation spectroscopy (DCS) for cerebral blood flow (CBF), provide the opportunity for portable bedside assessment of neonatal psychomotor function by measuring cortical hemodynamic response during motor function. This proposal aims to quantify the maturation of neonatal psychomotor function during feeding by combining real-time functional DOS/DCS (fDCS) metabolic imaging with mechanical quantification of oro-buccal motor behavior. High-frequency (200Hz) mechanical transduction will enable precise temporal correlation of elicited motor function with fDCS measures of cortical response. This work incorporates a novel implementation of advanced ?two-layer? DCS techniques to improve the cerebral specificity of CBF quantification by separating extra-cerebral tissue contributions. Using pediatric patient-specific measurements of extra-cerebral (EC) tissue thickness and optical properties we will address uncertainties in previous implementations due to population-derived assumptions. Retrospective analysis of concurrent, pre-operative cerebral perfusion measurements (DOS/DCS/MRI) in a large cohort of HLHS subjects (n=96) during hypercapnic challenge will permit optimization by maximizing correlation of measured hypercapnia CBF response with arterial spin-labeling (ASL) MRI (Aim 1). Immature white matter underlying the sensorimotor cortex is particularly susceptible to neonatal hypoxic- ischemic insult. Applying improved DCS techniques, we will conduct a prospective longitudinal study in HLHS neonates to understand the impact of white matter injury and developing psychomotor function in the vulnerable sensorimotor cortex on feeding behavior (Aim 2). Our clinical study will extend a larger Augmented Physiologic Monitoring study (IRB: 11-008191) that combines high-resolution anatomical MRI with longitudinal diffuse optical monitoring to study the etiology and timing of a common form of diffuse white matter injury, periventricular leukomalacia (PVL) in neonates with severe congenital heart disease (CHD). We will assess the correlation of post-operative PVL volume underlying the sensorimotor cortex with achievement of independent oral feeding at discharge. Consistent with learning-related attenuation of the sensorimotor oxy- hemoglobin response in adults, we hypothesize that HLHS neonates with better feeding behavior at discharge will exhibit attenuation of sensorimotor CBF response with time during post-operative recovery.