Grant Jensen flash freezes specimens to lock water in place then gets 3D images of cells in near-native state. He likens the result to a CT scan for protein complexes.

By combining advanced microscopes, new-generation cameras, innovative methods of acquiring raw data, and computational processing of the data, HHMI scientists and others are creating unprecedented depictions of biology’s magnificent marriage of form and function. Think of the leaps from still photography to movies, from black-and-white to color, and from silent to sound, and you begin to get a sense of how much more of life these pumped-up imaging tools are allowing researchers to see.

Janelia Farm fellows Davi Bock and Na Ji each describe the tools they built to get a closer view of the brain.

Neuroscientist Mark Schnitzer, an HHMI investigator at Stanford University, has been working with colleagues to extend the reach of their microscopes to watch ensembles of cells deep inside the brains of live, mobile animals. Schnitzer has been thinking hard about the evolution of imaging in biology. As he sees it, there has been a three-phase progression since the 17th century when the likes of Robert Hooke in England and Antonie van Leeuwenhoek in Holland first ushered microscopy into scientific investigations.

That first phase, based on what scientists could see in real time with their eyes peering through a microscope, lasted for centuries. First they recorded what they saw with hand drawings and then later with photographs. Their recorded images, says Schnitzer, were essentially data in pictorial form.

With phase 2 and the advent of digital cameras and laser-scanning techniques over the past few decades, “the image becomes a set of measurements,” says Schnitzer. Each pixel has associated with it digital values of light intensity, color, or some other parameter. More than just a pictorial rendition of what is visible, he notes, “the image becomes a numerical representation of reality.”

Photo: Jill Connelly / AP

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