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