Microscopy technique could enable more informative biopsies

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MIT and Harvard Medical School researchers have devised a way to image biopsy samples with much higher resolution — an advance that could help doctors develop more accurate and inexpensive diagnostic tests.

For more than 100 years, conventional light microscopes have been vital tools for pathology. However, fine-scale details of cells cannot be seen with these scopes. The new technique relies on an approach known as expansion microscopy, developed originally in Edward Boyden’s lab at MIT, in which the researchers expand a tissue sample to 100 times its original volume before imaging it.

This expansion allows researchers to see features with a conventional light microscope that ordinarily could be seen only with an expensive, high-resolution electron microscope. It also reveals additional molecular information that the electron microscope cannot provide.

In a paper appearing in the 17 July issue of Nature Biotechnology, Boyden and his colleagues used this technique to distinguish early-stage breast lesions with high or low risk of progressing to cancer — a task that is challenging for human observers. This approach can also be applied to other diseases: In an analysis of kidney tissue, the researchers found that images of expanded samples revealed signs of kidney disease that can normally only be seen with an electron microscope.

“Using expansion microscopy, we are able to diagnose diseases that were previously impossible to diagnose with a conventional light microscope,” says Octavian Bucur, an instructor at Harvard Medical School, Beth Israel Deaconess Medical Center (BIDMC), and the Ludwig Center at Harvard, and one of the paper’s lead authors.
MIT postdoc Yongxin Zhao is the paper’s co-lead author. Boyden and Andrew Beck, a former associate professor at Harvard Medical School and BIDMC, are the paper’s senior authors.

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