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(2)(i)) 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. Comparison of MRI measurements of global S(v)O(2), CBF, and CMRO(2) with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R(2)=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

Figure 1

(A) Sketch of an anesthetized and intubated patient entering the scanner with magnetic resonance imaging (MRI) compatible optical probe secured to the forehead. (B) Timeline of study protocol. Baseline diffuse optical spectroscopy (DOS) measures of deoxy-, oxy-, and total Hb concentrations (HbR, HbO₂, THC, respectively) and tissue oxygen saturation (StO₂) were obtained outside the MRI scanner. Subsequently, the patient was placed in the magnet first inhaling room air for 15 minutes; followed by addition of CO₂ to the gas mixture (fraction of inspired CO₂, 3%). Diffuse optical spectroscopy and diffuse correlation spectroscopy (DCS) data were acquired continuously in-magnet over this entire time period. Oximetry and phase-contrast MRI scans (1 minute in duration) were taken in-magnet at baseline and during hypercapnia. Arterial blood gases (ABG) were also obtained during room air and hypercapnia conditions. PC, phase-contrast.

Figure 2

Example time series showing diffuse optical spectroscopy (DOS) data (A) and diffuse correlation spectroscopy (DCS) data (B) obtained from a typical subject. The patient inhaled room air for approximately 15 minutes, at which time (denoted by black vertical line) CO₂ was added to the room air mixture. Typical parametric magnetic resonance (MR) images obtained at baseline (C, D) and hypercapnia (E, F) obtained during the period denoted by shaded gray rectangles. (C, E) Phase-difference images used for calculating venous oxygen saturation (S_vO₂) and, (D, F) velocity maps, both acquired in the superior sagittal sinus (SSS, red circle). BFI, blood flow index; THC, total hemoglobin concentration.

Figure 3

Correlations between resting-state magnetic resonance imaging and optical measurements: (A) venous oxygen saturation (S_vO₂) versus tissue oxygen saturation (StO₂); (B) cerebral blood flow (CBF) versus blood flow index (BFI); (C) cerebral oxygen consumption (CMRO₂) versus CMRO₂ index (CMRO_2i). The solid line represents the best linear fit to the data, while the dotted line indicates the line of identity. The gray ribbon denotes the 95% confidence interval for the linear fit. CMRO_2i is in units of 10⁻⁷ mL O₂/dL × cm²/second.

Figure 4

Correlations between magnetic resonance imaging and optical measurements in response to hypercapnia: (A) changes in oxygenation; (B) relative changes in cerebral blood flow (CBF) with respect to baseline; (C) relative changes in cerebral oxygen metabolism (CMRO₂) with respect to baseline. The solid line represents the best-fit line to the data, the dotted line indicates the line of identity. The gray ribbon denotes the 95% confidence interval for the linear fit.