Quantitative Near Infrared Spectroscopy Measurement of Cerebral Hemodynamics in Newborn Piglets

Abstract

Severely premature infants are often at increased risk of cerebral hemorrhage and/or ischemic injury caused by immature autoregulatory control of blood flow to the brain. If blood flow is too high, the infant is at risk of hemorrhage, whereas too little blood flow can result in ischemic injury. The development of a noninvasive, bedside means of measuring cerebral hemodynamics would greatly facilitate both diagnosis and monitoring of afflicted individuals. It is to this end that we have developed a near infrared spectroscopy (NIRS) system that allows for quantitative, bedside measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The technique requires an i.v. injection of the near infrared chromophore indocyanine green. Six newborn piglets, median age of 18 h (range 6 -54 h), median weight of 1.75 kg (range 1.5-2.1 kg), were studied. Measurements of CBF, CBV, and MTT were made at normocapnia, hypocapnia, and hypercapnia to test the technique over a range of hemodynamic conditions. The accuracy of our new approach has been determined by direct comparison with measurements made using a previously validated computed tomography technique. Paired t tests showed no significant difference between computed tomography and NIRS measurements of CBF, CBV, and MTT, and mean biases between the two methods were Ϫ2.05 mL·min Ϫ1 ·100 g Ϫ1 , Ϫ0.18 mL·100 g Ϫ1 , and 0.43 s, respectively. The precision of NIRS CBF, CBV, and MTT measurements, as determined by repeatedmeasures ANOVA, was 9.71%, 13.05%, and 7.57%, respectively. Since the first publication by Jobsis in 1977 (1), NIRS has been used in a variety of studies to investigate cerebral hemodynamics (2, 3). The underlying principles behind the use of NIRS to probe biologic media are relatively simple and have been described in detail elsewhere (1, 4 -8). There exist in biologic tissue four endogenous near infrared (NIR) light absorbers-oxy-Hb (HbO 2 ), deoxy-Hb (Hb), cytochrome oxidase (Cyt), and water. Because HbO 2 and Hb are generally present at relatively low concentrations in tissue, NIR light is able to penetrate tissue to a greater extent than other low-energy forms of light, in some cases up to distances of 8 -9 cm (6).As NIR light enters tissue, it is multiply scattered. The result of this scatter is that the total path length traveled by the NIR light is greater than the physical distance between the points of emission and detection. This extra distance can be accounted for using the differential path length factor (DPF), first described by Delpy et al. (9). With accurate knowledge of the DPF, a modified version of the Beer-Lambert law can be used to determine absolute changes in concentrations of NIR absorbers within tissue:where ⌬c is the change in concentration, ⌬A is the change in attenuation, ␣ is the extinction coefficient, L is the physical distance between emission and detection of NIR light, and B is the DPF. Measurement of concentration changes over time can

Measurement of Cerebral Oxidative Metabolism with Near-Infrared Spectroscopy: A Validation Study

“…Measuring reduced CMRO 2 may be one method for predicting the early onset of hypoxic-ischemic brain damage (Hagberg, 2004). Because of recent advances in hemodynamic measurements (Springett et al, 2001;Brown et al, 2002) and in the quantification of NIR chromophores in vivo (Matcher et al, 1994;Cooper et al, 1996), NIRS has the potential to offer a safe and rapid approach for quantitatively measuring CMRO 2 in newborns. In the present study, we found excellent agreement within a range of approximately 1.5 to 4.0 mL O 2 /mins per 100 g between our NIRS-based measurements of CMRO 2 and concurrent measurements of CMRO 2 obtained from arterial and sagittal sinus blood samples.…”

“…Furthermore, the same CBF measurement determined with the ICG/NIRS technique was used for both the NIRS and the blood sampling measurements of CMRO 2 . Since NIRS measurements of CBF have been previously validated (Brown et al, 2002), this study was essentially a validation of the NIRS-based AVDO 2 measurements. By including CBF and CBV measurements, AVDO 2 measurements could be expressed in the form of CMRO 2 measurements.…”

“…The absolute change in concentration of ICG in the NIR-illuminated region of interest was calculated using the modified BeerLambert law (equation (1)) with the DPF determined using the second derivative technique (Matcher et al, 1994). Since there was no ICG in the tissue before the injection, the absolute change in ICG measured with the NIRS system was simply the absolute concentration of ICG in the tissue (Brown et al, 2002).…”

“…Cerebral metabolic rate of Oxygen was determined from equation (2) using the measured AVDO 2 and CBF determined with the ICG/NIRS technique. It is acceptable to use the NIRS measurement of CBF as this technique has been previously validated (Brown et al, 2002).…”

“…Cerebral oxygenation has been studied by measuring deoxyhemoglobin (Hb), oxy-hemoglobin (HbO 2 ), and cytochrome oxidase concentrations (Kusaka et al, 2002;Hueber et al, 2001;Watzman et al, 2000;Brun et al, 1997;Ferrari et al, 1989;Springett et al, 2000). Near-infrared spectroscopy has also been used to measure CBF using the near-infrared (NIR) tracer indocyanine green (ICG) (Patel et al, 1998;Springett et al, 2001;Brown et al, 2002). By combining CBF and absolute Hb concentration measurements, our group has developed an NIRS method for measuring the CMRO 2 that is based on the Fick Principle (Siesjo, 1978).…”