Multiphoton microscopy has become an invaluable tool in neuroscience, allowing researchers to observe brain activity in real time with high-resolution imaging. A crucial aspect of many multiphoton microscopy studies is the effective delivery of chemical compounds, including imaging agents and drugs, to the brain. However, many of these compounds face a significant obstacle—the blood-brain barrier—which prevents them from being delivered through systemic administration. To overcome this challenge, a research team has developed an innovative cannula delivery system that enables the precise administration of compounds during extended live (in vivo) imaging via multiphoton microscopy. The system features a low-profile micropipette, or "cannula," implanted at a shallow angle of just 8 degrees, almost parallel to the brain's surface. This setup ensures that imaging agents can be delivered directly to the brain without interfering with the optical path needed for high-resolution imaging.

A significant challenge in optical imaging studies is that many fluorescent sensors and reporters used to study biological processes are not genetically encoded. These imaging agents often require direct infusion into the brain, which typically limits the ability to conduct longitudinal imaging studies. Researchers at Massachusetts General Hospital (Boston, MA, USA) have now introduced a shallow-angle, chronically implanted cannula for the delivery of imaging agents to the brain during long-term in vivo imaging sessions. To validate the efficacy of their cannula delivery system, the research team conducted a series of experiments. They successfully administered fluorescent cell markers into the brain while simultaneously imaging them using multiphoton microscopy.

Additionally, in mouse models of Alzheimer's disease, the team used a special dye, Fluoro-Jade C, to track degenerating neurons, and they also performed long-term imaging of brain tissue oxygen levels using a phosphorescent oxygen sensor. This technique marks a significant advancement for mouse cranial imaging windows, enhancing both dye delivery and the quality of imaging data. While this method is not entirely noninvasive, it presents a promising development for conducting longitudinal studies on brain function, disease progression, and potential treatments. The method offers researchers more accurate and reliable tools for a wide range of brain imaging applications. To facilitate broader adoption of this technology, the team has provided comprehensive guidance on the construction and implantation of the cannula in their study published in Neurophotonics. 

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