Forget all those hours of slicing your mouse brain in to sections, snapping images, and then manually putting them back together. Researchers have come up with a new device that images while it slices, and then puts them all together in a single, 3D atlas that can navigate just like Google Maps, with zoom and straight from a web browser – no extra software needed.
Invented by Bruce McCormick and his team at Texas A & M University’s Brain Networks Laboratory, the Knife-edge scanning microscope (KESM) combines the job of a tissue slicer and a microscope into a single process. First, the tissue is embedded into a plastic block mold. A custom-made diamond knife then slices the tissue into very thin sections (about half a micrometer thick). A laser illuminates the tissue along the knife’s edge as it’s being cut while images are rapidly captured through a microscope objective.
Because the sectioning and scanning is automated, entire brains scans are a simple matter of letting the KESM do its thing. It takes just under 100 hours to scan a 1 cubic cc block of tissue, which is about the size of a mouse brain. At 300 nm resolution, individual neurons in the brain slices are visible.
By themselves, each of the imaged slices of brain aren’t that interesting. It’s only when they’re digitally stitched back together do the images become meaningful. At last year’s Neuroinformatics meeting the team showed off exactly how they do that. Their Knife-Edge Scanning Microscope Brain Atlas is a web-based, 3D map of multiple mouse brains. And navigation through the brain architecture is powered by the Google Maps API so people can explore different brain areas as they would a city on Google Maps, with the ability to zoom out from an entire brain view down to individual neurons. The Atlas will be accessible online for other researchers without the need for special software. It can be explored using a web browser.
Knife-edge scanning can be used with all the forms of microscopy that researchers use, like bright-field and fluorescence microscopy with the fluorescence proteins that make puppies grow in the dark.
Right now mice are the mammals most amenable to genetic modification. Scientists insert, knock-out, or mutate genes to recreate human genetic disease in mice such as Alzheimer’s disease, diabetes, certain types of cancer, even depression. But creating brain atlases such as those from the Allen Brain Institute are largely the provence of large institutions with vast resources (the Allen Institute was founded on a $100 million seed donation from Microsoft co-founder Paul Allen). While whole-brain mapping of different types of protein will probably remain too labor-intensive for individual labs (the Allen Institute does this), the Knife-edge scanning microscope could be used to compare the gross anatomy of normal mouse and disease model brains.
At 2 TB per mouse brian, the data storage, sharing, and analysis should prove formidable. Analogous to the need for more powerful tools to analyze DNA sequence data following the breakthroughs that are democratizing genomics, I wouldn’t be surprised if anatomical studies follows the same path.