Cerebral Oxygen Metabolism in Neonates with Congenital Heart Disease Quantified by MRI and Optics

Abstract

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S v O 2 ) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO 2 in physiologic units. In addition, microvascular tissue oxygenation (StO 2 ) and indices of microvascular CBF (BFI) and CMRO 2 (CMRO 2i ) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO 2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O 2 /minute per 100 g, respectively. These CBF and CMRO 2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Keywords: cerebral blood flow; cerebral hemodynamics; diffuse optics; MRI; near-infrared spectroscopy; neonatal ischemia INTRODUCTION Congenital heart disease (CHD) affects B35,000 neonates each year in the United States. These patients suffer both short-and long-term neurologic sequelae. Periventricular leukomalacia is the most common cerebral injury found in this population. This type of injury is characterized by focal necrosis in the periventricular white matter, and it is associated with pyknotic glial nuclei and reactive gliosis. 1,2 During the early stages of brain development, the oligodendrocyte (brain glial cells) precursors are metabolically very active and highly susceptible to injury from reduced blood flow and oxygen delivery. Hence, hypoxiaischemia has been implicated as a major cause of this injury in CHD neonates.Periventricular leukomalacia leads to impaired myelination and has been linked to worse neurodevelopmental outcomes in premature infants and postulated to cause (at least in part) the impaired cognition and cerebral palsy commonly seen in this cohort of infants with CHD. 3,4 Quantification of the hemodynamic and metabolic state of these neonates via measurements of cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen consumption (CMRO 2 ) should provide valuable information toward understanding the interaction between cardiac pathophysiology and subsequent cerebral health. Potentially, such new knowledge could help predict and prevent adverse outcomes.

Optimizing Unanesthetized Cerebral Oxygen Consumption Measures: Comparison of NIRS and MRI Approaches in Neonates with Congenital Heart Disease

“…A similar trend is observed with our MRI results, showing a decreased CMRO2 relative to healthy subjects examined with a similar technique (8), and slightly higher CMRO2 than in anesthetized subjects (4,11) (Figure 2). SvO2 and OEF measurements correlate across modalities (r 2 =0.596, p=0.015 for SvO2; r 2 =0.525, p=0.027 for OEF) suggesting that these measures capture similar information and/or are relatively stable in this cohort (Figure 3).…”

“…The etiology of neurodevelopmental disorders is unknown but evaluation of the hemodynamic state of CHD infants pre-and post-surgically has become a focus with cerebral metabolic rate of oxygen consumption (CMRO2) identified as a key parameter for clinical evaluation (2-5). Jain et al (4) demonstrated correlations between magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) measures of CMRO2 pre-surgically when measured simultaneously in anesthetized neonates. We present NIRS and MRI-based measures of cerebral hemodynamics (OEF, CBF and CMRO2) in nine stable neonates with CHD.…”

Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks

“…When combined with CBF measurements by PC MRI and ASL, MR oximetry techniques can provide noninvasive quantification of global and regional CMRO 2 , respectively. In particular, global OEF and CMRO 2 measurement has been shown to be fast and reliable, and has shown clinical utility in neonatal imaging (De Vis et al, 2014;Jain et al, 2014;Liu et al, 2014). The developmental trajectories of global CBF, OEF and CMRO 2 at baseline observed in the present study are in excellent agreement with existing PET literature on developmental curves of CBF, CMRglu and CMRO 2 (Chiron et al, 1992;Chugani, 1998;Takahashi et al, 1999;Wintermark et al, 2004).…”

Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology

“…In particular, relative changes in CBF i due to hypercapnia correlated well with relative changes in blood flow in the common jugular veins and superior vena cava [40], and with perfusion arterial spin-labeling MRI [39,41]. More recently, baseline CBF i was also validated with baseline perfusion MRI in CHD [41].…”

“…Prior studies have shown that simultaneous FDNIRS-DCS and MRI measures of cerebral blood flow and cerebral oxygen metabolism correlate well in anesthetized, preoperative CHD neonates [39][40][41]. In particular, relative changes in CBF i due to hypercapnia correlated well with relative changes in blood flow in the common jugular veins and superior vena cava [40], and with perfusion arterial spin-labeling MRI [39,41].…”