Using near-infrared spectroscopy to measure cerebral metabolic rate of oxygen under multiple levels of arterial oxygenation in piglets

Abstract

Improving neurological care of neonates has been impeded by the absence of suitable techniques for measuring cerebral hemodynamics and energy metabolism at the bedside. Currently, near-infrared spectroscopy (NIRS) appears to be the technology best suited to fill this gap, and techniques have been proposed to measure both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). We have developed a fast and reliable bolus-tracking method of determining CMRO2 that combines measurements of CBF and cerebral venous oxygenation [venous oxygen saturation (CSvO2)]. However, this method has never been validated at different levels of arterial oxygenation [arterial oxygen saturation (SaO2)], which can be highly variable in the clinical setting. In this study, NIRS measurements of CBF, CSvO2, and CMRO2 were obtained over a range of SaO2 in newborn piglets (n=12); CSvO2 values measured directly from sagittal sinus blood samples were collected for validation. Two alternative NIRS methods that measure CSvO2 by manipulating venous oxygenation (i.e., head tilt and partial venous occlusion methods) were also employed for comparison. Statistically significant correlations were found between each NIRS technique and sagittal sinus blood oxygenation (P<0.05). Correlation slopes were 1.03 (r=0.91), 0.73 (r=0.73), and 0.73 (r=0.81) for the bolus-tracking, head tilt, and partial venous occlusion methods, respectively. The bolus-tracking technique displayed the best correlation under hyperoxic (SaO2=99.9±0.03%) and normoxic (SaO2=86.9±6.6%) conditions and was comparable to the other techniques under hypoxic conditions (SaO2=40.7±9.9%). The reduced precision of the bolus-tracking method under hypoxia was attributed to errors in CSvO2 measurement that were magnified at low SaO2 levels. In conclusion, the bolus-tracking technique of measuring CSvO2, and therefore CMRO2, is accurate and robust for an SaO2>50% but provides reduced accuracy under more severe hypoxic levels.

The correlation between brain near-infrared spectroscopy and cerebral blood flow in piglets with intracranial hypertension

“…Walter et al (20) compared blood flow measured by colored microspheres with that determined by using radioactive microspheres in uninjured piglets and noted an excellent correlation. Our values for CBF are comparable to those reported by others (16), as are our measurements of CMRO 2 (2,17). In addition, as shown in the sham-operated control animals, multiple injections of the microspheres did not alter the NIRS measurements or reduce CBF.…”

“…To obtain hemispheric CBF, we used an average of those brain regions providing the majority of blood flow through the internal jugular vein assuming each provided an equal contribution. Although this may have introduced some error, this average is likely a reasonable approximation and our values for CMRO 2 are similar to those reported by others (2,17). Nonetheless, the measurements of CMRO 2 , CMR glu , and lactate production were global, and it is possible that there were regional differences that were not detected.…”

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

“…where μ a ðλÞ is the absorption coefficient measured at wavelength λ, c i is the concentration of the i'th chromophore, ε i ðλÞ is the extinction coefficient at λ,ε H 2 O is the the mean pure water absorption coefficient from the calibration at λ, S i is the score of the i'th loading vector, and P i ðλÞ is a loading vector of the pure water at λ. In the first step, a least-square optimization algorithm (built around the function fminsearchbnd 34 ) was used to extract the score of one pure water loading vector, i.e., PC, and concentrations of oxy-and deoxy-hemoglobin at baseline temperature by assuming a known water concentration of 95% and 85% for phantom and tissue experiments, respectively, 35,36 The optimization function was bound constrained, where bounds were applied to the recovered values to limit the search for oxy-and deoxy-hemoglobin concentrations to be in the range of 30-60 μM 37 and 5-25 μM, 38,39 respectively. Note that the extinction coefficients of pure water as a function of temperature as well as those of oxy-and deoxy-hemoglobin used in this study were taken from the literature.…”

Quantitative assessment of global cerebral metabolic rate of oxygen (CMRO2) in neonates using MRI

“…Positron emission tomography (PET) is the gold standard for the measurement of the cerebral metabolic rate of oxygen (CMRO 2 ) in adults , but its applicability in neonates is limited by the concerns of radiation safety in this population. Near‐infrared spectroscopy (NIRS) approaches have been proposed to assess CMRO 2 , but have not been widely accepted because assumptions with regard to the arteriovenous volume ratio are required, and it is difficult to determine the light penetration depth. Other potential CMRO 2 methods, such as 13 C NMR , 17 O NMR and biophysical model‐based MRI methods , have only begun to be explored in adults, and are not ready to be used in neonates.…”