A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Freely Behaving Mice

Abstract

Wearable technologies for functional brain monitoring in freely behaving subjects would advance our understanding of cognitive processing and adaptive behavior. Existing technologies are lacking in this capability or need procedures which are invasive and/or otherwise impede brain assessments during social behavioral conditions, exercise, and sleep. In response we developed a complete system combining cerebral blood flow (CBF) measurement, O 2 and CO 2 supplies, and behavior recording for use on conscious, freely behaving mice. An innovative diffuse speckle contrast flowmetry (DSCF) device and associated hardware were miniaturized and optimized for small subject applications. The installation and use of this wearable, fiber-free, near-infrared DSCF head-stage/probe required no craniotomy, invasive probe implantation, or restraints of awake animals. Significant correlations were found between measurements with the new DSCF design and an optical standard. The system successfully and repeatedly detected CBF responses to CO 2induced hypercapnia in both anesthetized and moving mice. Collecting CBF and activity information together during natural behaviors provides realistic physiological results and opens the path to exploring their correlations with pathophysiological conditions.

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

“…3a-3d ), indicating the difference in detection sensitivity of the two optical sensors. These results agreed with our previous findings in concurrent DCS/DSCF measurement of rCBF in anesthetized mice 33,34 . Generally, the expensive single-photon-counting APD has a better sensitivity than the low-cost NanEye camera.…”

“…Generally, the expensive single-photon-counting APD has a better sensitivity than the low-cost NanEye camera. However, other factors may also impact the measurement, including tissue heterogenous response, probe location, detector window size, and methodology difference 34,35 .…”

“…To overcome these challenges, we have recently developed a NIR diffuse speckle contrast flow oximetry (DSCFO) that provides a low-cost, fiber-free, wearable, and compact approach for continuous monitoring blood flow and oxygenation variations in freely behaving subjects 31–34 . DSCFO uses two small laser diodes as focused-point sources for deep tissue penetration and a tiny CMOS camera as a high-density two-dimensional (2D) detector array to detect spontaneous spatial fluctuations of diffuse laser speckles for blood flow detection, and light intensity attenuations at different wavelengths for blood oxygenation measurement.…”

“…To overcome these challenges, we have recently developed a NIR diffuse speckle contrast flow oximetry (DSCFO) that provides a low-cost, fiber-free, wearable, and compact approach for continuous monitoring blood flow and oxygenation variations in freely behaving subjects [31][32][33][34] .…”

“…The connections between the wearable probe and DSCFO device are all flexible electrical wires (i.e., fiber free), enabling continuous monitoring of tissue blood flow and oxygenation variations in freely behaving subjects. The sensitivity and accuracy of DSCFO for blood flow and oxygenation measurements have been previously verified against established NIRS and DCS technologies in tissue-simulating phantoms, human forearm muscles during arterial cuff-occlusion, and mouse brains under anesthesia and during freely behavior tests with hypercapnia challenges [31][32][33][34][35] .…”