The future of noninvasive neonatal brain assessment: the measure of cerebral blood flow by diffuse correlation spectroscopy in combination with near-infrared spectroscopy oximetry

Abstract

We read with interest the article assessing the association among partial pressure of carbon dioxide (pCO2), cerebral blood flow (CBF), and cerebral autoregulation in preterm infants <29 weeks gestational age [1]. CBF might be increased when pCO2 is greater than 55 mmHg in the first 4 days of life, and autoregulation might be impaired at low levels of pCO2 on day of life one. In this study the regional frontal cortex oxyhemoglobin saturation (rScO2, %) was utilized as a surrogate marker of CBF assuming stable oxygenation and metabolic demand. Cortical oxygenation has been successfully monitored noninvasively and transcranially in the intensive care unit and in the operative room by commercial near-infrared spectroscopy (NIRS) brain oximeters. These oximeters provide the intensivists with a continuous measure of rScO2. Since the first rScO2 observations in preterm infants [2], big progresses have been made in this field. So far, validation studies have been performed regarding the reliability of using cerebral oximetry either on infants or adults [3]. In addition, the rScO2 measurement on newborns has recently been validated by using a new magnetic resonance imaging sequence [4]. It is well known that, at any given time, rScO2 is the result of a range of different physiological factors especially CBF. Therefore, it would be very important to measure directly CBF. In the last twenty years a complementary optical technique, near-infrared diffuse correlation spectroscopy (DCS), has been developed for the continuous measurement of blood flow in tissue. Successful applications of it to human newborn brain cortex have been already demonstrated [5]. DCS (using the temporal fluctuations of diffusely reflected light to quantify the motion of moving scatterers, which in tissue is dominated by the motion of red blood cells) provides a noninvasive estimate of deep tissue microvascular blood flow as a blood flow index. By combining quantitative oximetry, based on frequency–domain multi-distance spectroscopy or timeresolved reflectance spectroscopy (both capable of measuring the tissue absorption and scattering coefficients) [6, 7], and DCS flow measures, the tissue regional oxygen metabolic rate (MRO2i) can be quantified. The latter is a parameter closely linked to underlying physiology and pathological states. The MRO2i is an important parameter that has been investigated in the human newborn brain given the strong dependence of this organ on the aerobic metabolism. The coupling of brain oximetry with DCS offers the great advantage to discriminate temporal variations of rScO2 in conjunction with fine microvascular CBF fluctuations. DCS at its present state has some limitations that can be summarized as follows: (1) the complexity and the high cost of the instrumentation; (2) the inability to provide absolute values of CBF; (3) the negative interference of systemic variations of scalp blood flow in the calculation of CBF; (4) measurements of deep structures are not allowed; (5) the vulnerability to motion artifacts, and 6) the critical contact pressure between the optical probe and the tissue surface. Several strategies are under development to overcome these limitations. Time-gated strategies and/or the use of longer wavelengths should make available the measurement of CBF at different depths [8, 9]. Portable low-cost systems, adopting advanced algorithms, should be soon commercialized for being used routinely. In the near future, DCS and other diffuse optical tools, like wearable high-density diffuse optical tomography [10], are expected to increase our understanding about * Marco Ferrari [email protected]