Chronic monitoring of cortical hemodynamics in behaving, freely-moving rats using a miniaturized head-mounted optical microscope

Growing interest within the neurophysiology community in assessing healthy and pathological brain activity in animals that are awake and freely-behaving has triggered the need for optical systems that are suitable for such longitudinal studies. In this work we report label-free multi-modal imaging of cortical hemodynamics in the somatosensory cortex of awake, freely-behaving rats, using a novel head-mounted miniature optical microscope. The microscope employs vertical cavity surface emitting lasers (VCSELs) at three distinct wavelengths (680 nm, 795 nm, and 850 nm) to provide measurements of four hemodynamic markers: blood flow speeds, HbO, HbR, and total Hb concentration, across a > 2 mm field of view. Blood flow speeds are extracted using Laser Speckle Contrast Imaging (LSCI), while oxygenation measurements are performed using Intrinsic Optical Signal Imaging (IOSI). Longitudinal measurements on the same animal are made possible over the course of > 6 weeks using a chronic window that is surgically implanted into the skull. We use the device to examine changes in blood flow and blood oxygenation in superficial cortical blood vessels and tissue in response to drug-induced absence-like seizures, correlating motor behavior with changes in blood flow and blood oxygenation in the brain.