Multiphoton microscopy and molecular sensors

Ultrafast molecular sensors, used with high-speed multiphoton microscopy, enable direct visualization of chemical changes in the brain. Rumiana Bakalova from the Molecular Imaging Center of the National Institute of Radiological Sciences in Chiba, Japan, has reviewed advancements in these sensors, with emphasis on studying regional blood flow and metabolism by visualizing nexuses of synapses, astrocytes and blood vessels.

Bakalova points out that the calcium-ion sensor developed by Dr. Maiken Nedergaard and others is quantitative and that it could enable simultaneous real-time detection of calcium-ion release and blood vessel dilation when brain cells communicate. She notes that this process requires a high-speed CCD camera because it occurs in milliseconds. She also describes an ultrafast and highly selective sensor developed by Stephen J. Lippard and others that exhibits 11 times more fluorescence when it contacts nitric oxide.

Finally, Bakalova calls our attention to several zinc-ion sensors that have been used successfully in vivo. Zinc-ion sensors are important because the ion is essential in the brain and because it has been found to play a role in strokes and neurodegenerative diseases such as Alzheimer’s.

She notes that molecular probes used in brain studies should not be toxic or change brain chemistry and that they should penetrate the blood-brain barrier, although creating such probes is difficult. Probes should rapidly, sensitively and selectively reach targets, and they ideally should exhibit strong fluorescence signals and emit in the visible or near-IR regions.

She adds that gold quantum dots are promising probes in brain studies because they strongly fluoresce, they are not toxic, and they might be able to penetrate the blood-brain barrier, although the latter property needs further verification. (Brain Research Bulletin, June 15, 2007, pp. 150-153.)