Imaging the brain activity of living, freely moving animals provides valuable information for studying neurological disorders. However, it can be difficult to conduct these imaging studies long-term, especially when working with an animal model as small as a mouse. A new head-mounted brain microscope developed by researchers at the Southern University of Science and Technology uses photoacoustic technology and a lightweight, detachable design to enable long-term neurovascular imaging in living, freely moving mice.
The new probe is based on a previous wearable probe designed for use on free moving rats. This past design, based on optical resolution photoacoustic microscopy (ORPAM), performed well but was too large to use with mice and had to be permanently fixed rather than being detachable. After using optical simulation calculations to optimize the light path of the microscope and selecting high-performance miniature components, including an aspheric lens, micro-electro-mechanical-system (MEMS) scanner and customized miniaturized piezoelectric ultrasonic detector, the team managed to produce a new ORPAM probe weighing just 1.8 grams, or less than 10% of an adult mouse’s body weight.
The miniaturized head-mounted microscope has a resolution of 2.8 microns and a field of view of 3x3 mm2. The ORPAM technology, in contrast to typical multi-photon or fluorescence imaging systems, allows capillary-level resolution of the brain’s vascular network without the use of tags or labels. The probe was made detachable by incorporating three pairs of magnets that connect the imaging component to a lightweight base attached to the mouse’s skull. This system allows researchers to monitor the vascular network and hemodynamics of the mouse cerebral cortex over time by detaching the probe after imaging and reinstalling it for repeated observations. In testing their design, the researchers were able to image vascular networks in the cerebral cortex for a period of 40 minutes as well as conduct long-term monitoring experiments lasting a total of seven days. This research was published in Optics Letters.
“Epilepsy, Alzheimer’s disease and Parkinson’s disease can all seriously interrupt neurovascular coupling—the link between neural activity and subsequent changes in cerebral blood flow,” said research team leader Lei Xi. “Our new probe is ideal for studying neurovascular coupling because it has the potential to capture the dynamics of both neuron and vascular networks simultaneously.”
The researchers plan to further improve their design to achieve video-rate imaging speed and a field of view large enough to capture the entire mouse cerebral cortex, Xi said.
Photo: The head-mounted photoacoustic microscope is lightweight and detachable, allowing repeated imaging of brain activity in living, freely moving mice. Credit: Lei Xi, Southern University of Science and Technology