A Wearable Fiber-Free Optical Sensor for Continuous Measurements of Cerebral Blood Flow and Oxygenation

Wearable technologies for continuous monitoring of cerebral hemodynamics in freely behaving subjects not only advance our understanding of cognitive processing and adaptive behavior, but also provide vital information for diagnosis and therapeutic assessment of cerebral diseases associated with hypoxia/ischemia. Wearable near-infrared diffuse optical techniques have been used at the bedside to probe deep cerebral hemodynamics, including near-infrared spectroscopy (NIRS) for cerebral oxygenation measurement and diffuse correlation spectroscopy (DCS) for cerebral blood flow (CBF) measurement, respectively. However, most systems are relatively large and expensive, and use rigid fiber-optic probes that significantly constrain subject’s movement. A novel, wearable, fiber-free diffuse speckle contrast flow-oximetry (DSCFO) system was developed in our laboratory for simultaneous measurements of CBF and cerebral oxygenation in freely behaving subjects. DSCFO uses inexpensive near-infrared laser diodes at two different wavelengths as focused-point sources and a tiny complementary metal oxide semiconductor (CMOS) camera as a high-density 2D detector array to quantify spatial fluctuations of diffuse laser speckles, resulting from movement of red blood cells (i.e., CBF). Moreover, light intensity variations measured at two wavelengths enable quantification of oxy- and deoxy- hemoglobin concentration changes (Δ[HbO2] and Δ[Hb]). Connections between the wearable probe and DSCFO device were all flexible electrical wires (i.e., fiber-free), enabling continuous measurement in freely behaving subjects. Tissue simulating phantom tests verified the accuracy of DSCFO in measuring tissue absorption coefficient and Intralipid particle flow variations. In vivo tests in human forearms detected substantial changes in blood flow, Δ[HbO2], and Δ[Hb] during the artery occlusion on their upper arms. The DSCFO probe was then downscaled using 3D printing technique and optimized for continuous monitoring of relative changes in CBF (rCBF) in freely behaving mice. rCBF variations induced by the hypercapnia (8%CO2) and behaviors (walking, grooming, and climbing) were detected by DSCFO. Furthermore, the DSCFO probe was scaled up and adapted for larger heads of neonatal piglets and human preterm infants. Neonatal piglets were measured concurrently by the DSCFO and dual-wavelength DCS flow- oximetry devices during hypercapnia, asphyxia (100%CO2), and transient unilateral andbilateral common carotid artery ligations. Significant correlations were observed between the two measurements, demonstrating the capability of DSCFO for continuous assessment of cerebral hemodynamics. To demonstrate clinical safety and feasibility of DSCFO, a pilot study was conducted in the neonatal intensive care unit (NICU), where rCBF, Δ[HbO2], and Δ[Hb] were continuously monitored in preterm infants during intermittent hypoxia. The resulting rCBF, Δ[HbO2], and Δ[Hb] did not always follow the changes in arterial blood oxygen saturation (SpO2) measured by a finger pulse oximeter, suggesting the necessity of direct cerebral monitoring and the importance of multi-parameter measurements. With further optimization and testing in large populations, we expect to offer a wearable and affordable brain monitoring tool for basic research in laboratories and translational applications in clinics. Overall, DSCFO provides many advanced unique features over other competitive technologies, including a wearable, fiber-free, multiscale probe, an inexpensive and portable device, multi-parameter measurement, quick data acquisition, and real-time data analysis and reporting.