Background-This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy-and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S v O 2 ) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO 2 in physiologic units. In addition, microvascular tissue oxygenation (StO 2 ) and indices of microvascular CBF (BFI) and CMRO 2 (CMRO 2i ) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO 2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O 2 /minute per 100 g, respectively. These CBF and CMRO 2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Keywords: cerebral blood flow; cerebral hemodynamics; diffuse optics; MRI; near-infrared spectroscopy; neonatal ischemia INTRODUCTION Congenital heart disease (CHD) affects B35,000 neonates each year in the United States. These patients suffer both short-and long-term neurologic sequelae. Periventricular leukomalacia is the most common cerebral injury found in this population. This type of injury is characterized by focal necrosis in the periventricular white matter, and it is associated with pyknotic glial nuclei and reactive gliosis. 1,2 During the early stages of brain development, the oligodendrocyte (brain glial cells) precursors are metabolically very active and highly susceptible to injury from reduced blood flow and oxygen delivery. Hence, hypoxiaischemia has been implicated as a major cause of this injury in CHD neonates.Periventricular leukomalacia leads to impaired myelination and has been linked to worse neurodevelopmental outcomes in premature infants and postulated to cause (at least in part) the impaired cognition and cerebral palsy commonly seen in this cohort of infants with CHD. 3,4 Quantification of the hemodynamic and metabolic state of these neonates via measurements of cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen consumption (CMRO 2 ) should provide valuable information toward understanding the interaction between cardiac pathophysiology and subsequent cerebral health. Potentially, such new knowledge could help predict and prevent adverse outcomes.

Diffuse optics has proven useful for quantitative assessment of tissue oxy-and deoxyhaemoglobin concentrations and, more recently, for measurement of microvascular blood flow. In this paper, we focus on the flow monitoring technique: diffuse correlation spectroscopy (DCS). Representative clinical and pre-clinical studies from our laboratory illustrate the potential of DCS. Validation of DCS blood flow indices in human brain and muscle is presented. Comparison of DCS with arterial spin-labelled MRI, xenon-CT and Doppler ultrasound shows good agreement (0.50 < r < 0.95) over a wide range of tissue types and source detector distances, corroborating the potential of the method to measure perfusion non-invasively and in vivo at the microvasculature level. Alloptical measurements of cerebral oxygen metabolism in both rat brain, following middle cerebral artery occlusion, and human brain, during functional activation, are also described. In both situations, the use of combined DCS and diffuse optical spectroscopy/near-infrared spectroscopy to monitor changes in oxygen consumption by the tissue is demonstrated. Finally, recent results spanning from gene expression-induced angiogenic response to stroke care and cancer treatment monitoring are discussed.

Abstract. We employ a hybrid diffuse correlation spectroscopy ͑DCS͒ and near-infrared spectroscopy ͑NIRS͒ monitor for neonates with congenital heart disease ͑n =33͒. The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow ͑rCBF DCS ͒; and oxygen metabolism ͑rCMRO 2 ͒. Concurrent measurements with arterial spin-labeled magnetic resonance imaging ͑rCBF ASL-MRI , n =12͒ cross-validate rCBF DCS against rCBF ASL-MRI , showing good agreement ͑R = 0.7, p = 0.01͒. The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population.