The first-ever detachable head-mounted photoacoustic microscope for imaging brain activity in freely moving mice has been developed by scientists. The device has an option to be removed once imaging is over, thus enabling long-term studies that can disclose crucial insights into neurodegenerative diseases and other neurological disorders.
Image Credit: Shutterstock.com/Konstantin Kolosov
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. 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.
Lei Xi, Research Team Leader, Southern University of Science and Technology
The weight of the new microscope probe is only 1.8 g and it has been made based on optical resolution photoacoustic microscopy (ORPAM). It has the ability to capture the functional and anatomical dynamics of the brain without using fluorescent labels or tags. In the Optica Publishing Group journal Optics Letters, Xi and collaborators explain how they improved the design of the new probe to make it very light for use in freely moving mice.
Head-mounted microscopes that use multi-photon or fluorescence imaging primarily capture the activities of single neurons. Our ORPAM probe can capture cerebral vascular network and hemodynamics of large portions of the cerebral cortex with capillary-level resolution without requiring any labels.
Lei Xi, Research Team Leader, Southern University of Science and Technology
Miniaturizing a Microscope
The new study is based on a wearable ORPAM probe built by the scientists earlier for freely moving rats. Even though it showed good performance, it had to be fixed permanently on the rat and was too large and bulky to be carried around by mice. These are considered to be the preferred animal models for several brain studies.
To create a smaller probe, the scientists made use of optical simulation calculations to cautiously improve the complete light path of the microscope. Also, they chose selected high-performance miniature components, such as an aspheric lens, micro-electro-mechanical-system (MEMS) scanner and tailored miniaturized piezoelectric ultrasonic detector.
The weight of the new probe is below 10% of an adult mouse’s body weight, and it features a resolution of around 2.8 microns. Also, it can image a huge field of view of 3 × 3 mm2. To make it detachable, three pairs of magnets were incorporated by the researchers.
These magnets connect the imaging probe with a lightweight mounting base fixed to the skull of the mouse. The probe can be directly removed once imaging is over and further reinstalled later. This allows repeated and long-term monitoring of freely moving animals.
Long-Term Imaging
Once the evaluation of the performance of the probe on a synthetic material that mimics soft tissue was completed, the scientists utilized it to image vascular networks in the cerebral cortex of a mouse for around 40 minutes. They also performed long-term monitoring experiments that lasted for seven days. The outcomes from such tests demonstrated that the probe has the ability to offer stable and high-quality ORPAM images in freely moving mice.
In the future, we intend to develop a probe with capillary-level resolution, video-rate imaging speed and a field of view large enough to capture the entire mouse cerebral cortex. We want to push the performance of the probe so that even more can be learned about brain activity and how it might relate to disease and health.
Lei Xi, Research Team Leader, Southern University of Science and Technology
Journal Reference:
Guo, H., et al. (2021) Detachable head-mounted photoacoustic microscope in freely moving mice. Optics Letters. doi.org/10.1364/OL.444226.