A detachable head-mounted microscope allows images of brain activity in mice

The first-ever detachable-head-mounted photoacoustic microscope for imaging brain activity in freely moving mice has been developed by scientists. The device has the ability to be removed once imaging is complete, enabling long-term studies that can reveal crucial information about neurodegenerative diseases and other neurological disorders.

Image Credit: Shutterstock.com/Konstantin Kolosov

Epilepsy, Alzheimer’ss disease and parkinsons disease can seriously disrupt neurovascular coupling – the link between neural activity and subsequent changes in cerebral blood flow. Our new probe is ideal for studying neurovascular coupling as it has the potential to simultaneously capture the dynamics of neural and vascular networks.

Lei Xi, Research Team Leader, Southern Science and Technology University

The weight of the new microscope probe is only 1.8g and it was fabricated based on optically resolved photoacoustic microscopy (ORPAM). It has the ability to capture the functional and anatomical dynamics of the brain without using fluorescent tags or labels. In the magazine Optica Publishing Group Optical letters, Xi and his collaborators explain how they improved the design of the new probe to make it very light for use on freely moving mice.

Head-mounted microscopes that use multiphoton or fluorescence imaging primarily capture the activities of single neurons. Our ORPAM probe can capture the cerebrovascular network and hemodynamics of large parts of the cerebral cortex with capillary-level resolution without the need for labels.

Lei Xi, Research Team Leader, Southern Science and Technology University

Miniaturize a microscope

The new study is based on a wearable ORPAM probe the scientists built earlier for freely moving rats. Although it showed good performance, it had to be permanently attached to the rat and was too big and cumbersome to be carried by mice. These are considered the preferred animal models for several brain studies.

To create a smaller probe, the scientists used optical simulation calculations to carefully enhance the full light path of the microscope. In addition, they chose selected high-performance miniature components, such as an aspherical lens, a micro-electro-mechanical system (MEMS) scanner, and a custom-made miniaturized piezoelectric ultrasonic detector.

The weight of the new probe is less than 10% of the body weight of an adult mouse and its resolution is approximately 2.8 microns. Also, it can image huge 3×3mm field of view2. To make it detachable, three pairs of magnets were incorporated by the researchers.

These magnets connect the imaging probe to a lightweight mounting base attached to the skull of the mouse. The probe can be directly removed after imaging is completed and reinstalled later. This allows for repeated, long-term monitoring of freely moving animals.

Long term imaging

After evaluating the probe’s performance on a synthetic soft-tissue-mimicking material, the scientists used it to image vascular networks in the cerebral cortex of a mouse for about 40 minutes. They also performed long-term monitoring experiments that lasted seven days. The results of these 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 imaging speed, and a field of view large enough to capture the entire mouse cerebral cortex. We want to improve the performance of the probe in order to learn even more about brain activity and its link to disease and health..

Lei Xi, Research Team Leader, Southern Science and Technology University

Journal reference:

Guo, H. et al. (2021) Detachable head-mounted photoacoustic microscope in free-moving mice. Optical letters. doi.org/10.1364/OL.444226.

Source: https://www.optica.org/en-us/home/

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