This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Impaired neurodevelopmental outcome has been observed for survivors of neonatal heart surgery for congenital heart defects. There is prior evidence indicating the importance of preoperative cerebral well-being on the observed outcome. Furthermore, it is well known that the surgical parameters which include cardiac by-pass, deep-cooling and arrest need to be optimized via real-time, bed-side monitoring. A crucial parameter that is largely inaccessible is the cerebral blood flow (CBF). We have recently developed diffuse correlation spectroscopy (DCS) for non-invasive, continuous measurement of relative CBF. In this work, we report our first results from its clinical application to neonates where it was combined with diffuse optical spectroscopy (DOS) for measurement of blood oxygenation and cerebral oxygen metabolism. In this two-cohort study, neonates with severe congenital heart defects scheduled for cardiac surgery were measured preoperatively to assess cerebral C02 reactivity and autoregulation. The first cohort (n=44) was measured during an extended period of hypercapnia in the MRI magnet and DCS measurement was validated against arterial spin-labeling MRI measure of CBF showing good agreement between two methods. An impairment of C02 reactivity was not observed due to large range of C02 reactivity values reported in the literature and the sample size. The second cohort is now being recruited (n=18) for a more extended monitoring including the preoperative preparation period and statistically comparing the findings with the post-operative outcome measures. We have monitored cerebral blood flow and oxygenation changes in this new cohort for 12 hours immediately following cardiac surgery using bedside optical techniques. We are investing periods of damaged cerebral autoregulation, i.e. periods of time in which cerebral blood flow and mean arterial pressure are highly correlated. Additionally, a week after surgery, the subjects undergo a post-surgical anatomical MRI scan to determine the extent, if any, of hypoxic-ischemic white matter injury. Phase 3 of this study aims to investigate absolute optical properties of these patients in order to more accurately quantify changes in tissue oxygen saturation (StO2), and cerebral metabolic rate of oxygen extraction (CMRO2). Currently, we make assumptions on baseline optical properties of these infants based on published values, which are very sparse, in order to approximate StO2 and CMRO2. We will design and implement a new optical probe to assess these properties on each patient as part of our existing protocol to definitively evaluate StO2 and CMRO2.