The new probe builds on the group’s earlier research creating ORPAM devices. The group has previously created a wearable ORPAM device, but at 8 grams, it was too heavy for the mice to wear and still move freely. Cutting the weight to 1.8 grams and more than doubling the size of the field of view, the new microscope is the first to allow ORPAM imaging in freely moving mice.

The researchers hope the new detachable probe will open the doors for long-term studies of neurological disorders and neurodegenerative diseases that can be induced by blood flow restriction, such as epilepsy, Alzheimer disease, and Parkinson disease.

Detaching the probe

Drawing of probe components

Schematic of probe configuration. [Image: H. Guo et al., Opt. Lett. 46, 6055 (2021)]

The probe, which contains an optical fiber, a miniaturized optical scanner and a small piezo-electric ultrasonic transducer, also differs from its predecessor in its removability. Using three pairs of magnets, the probe can be repetitively attached and detached to a permanent mount on a mouse’s skull.

The researchers have tested the probe on synthetic tissue and on mice, where it imaged vascular networks over 40 minutes. A seven-day study was also conducted, showing the probe’s potential for long-term research.

The researchers plan to continue improving the device, aiming to boost the resolution and imaging speed. This will help researchers better study links between brain activity and diseases.

“The work in this paper is our first step. In future, we will develop a probe with better performance, such as capillary-level resolution, video-rate imaging speed and a large field of view to cover the entire cerebral cortex,” Xi said. “Based on this new probe, we will perform more meaningful studies to find out more secrets of the brain.”