Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.

Abstract:Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO 2 ). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBF i ), cerebral oxygen metabolism (CMRO 2i ) and SO 2 ; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO 2i and CBF i , which returned to baseline when stable. However, SO 2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO 2 alone. References and links 1. J. I. E. Hoffman and S. Kaplan, "The incidence of congenital heart disease," J. Am. Coll. Cardiol. 39, 1890-1900 A. Rappaport, and D. Wypij, "Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery," J. Thorac. Cardiovasc. Surg. 135, 347-54, 354.e1-4 (2008).

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO 2 ). Thus, measures of CMRO 2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO 2 an ideal target for bedside measurement of brain health.Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO 2 ) as a surrogate for cerebral oxygen consumption. However, SO 2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO 2 are not sensitive enough to detect brain injury hours after the insult 1,2 , because oxygen consumption and delivery reach equilibrium after acute transients 3 . We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO 2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBF i ) to yield an index of CMRO 2 (CMRO 2i ) 4,5 .With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.