Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occuring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (ΔHbR) is equal to 16–22% of the cortical contribution to the total hemoglobin signal change (ΔHbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (ΔHbO) is equal to 73–79% of the cortical contribution to the ΔHbT signal. These results suggest that ΔHbT is far less sensitive to pial vein contamination and therefore, it is likely that the ΔHbT signal provides better spatial specificity and should be used instead of ΔHbO or ΔHbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution.

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO 2i ) and CBF indices (CBF i ) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO 2 ) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO 2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO 2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. Keywords: cerebral blood circulation; cerebral hemoglobin oxygen saturation; cerebral metabolic rate of oxygen consumption; near infrared spectroscopy; neonatal hypoxic ischemic encephalopathy; therapeutic hypothermia INTRODUCTION Neonatal hypoxic ischemic encephalopathy (HIE) occurs in B2 to 3 per 1,000 live births in the USA, with devastating consequences including neurodevelopmental disabilities such as cerebral palsy, life-long cognitive impairment, and epilepsy.1 In HIE, there is a period of reduced blood flow (ischemia) and oxygen delivery (hypoxia) followed by reperfusion with transient energy recovery, and then a secondary energy failure.2 Treatment is aimed at preventing the cascade of events that begin with reperfusion and lead to secondary energy failure and inevitable cell death; this is the 'window of opportunity.' 3 Theories for injury mechanisms in this window suggest a central role for excitotoxicity and oxidative stress with the injury evolving over hours to weeks.2 Therapeutic hypothermia (TH) is the treatment of choice for HIE, as it is the only treatment with proven efficacy and acts through a variety of mechanisms, including those associated with decreased neuronal energy metabolism. 4 Although early studies showed that TH decreased rates of both mortality and disability, recently published long-term outcomes have demonstrated significance only for decreased mortality rates.5 In addition, a recent

Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO2) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BFix) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO2 and CBV, relative values of BFix, and relative cerebral metabolic rate of oxygen (rCMRO2) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO2 correlates with chronological age (r=−0.54, P value ⩽0.001) but not with PMA (r=−0.07), whereas BFix and rCMRO2 correlate better with PMA (r=0.37 and 0.43, respectively, P value ⩽0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO2 are more accurate biomarkers of the brain development than SO2 in the premature newborns.