July 6, 2001

An image of a breast tumor's blood vessels as seen through the new microscope.

A powerful new high-resolution, three-dimensional imaging tool is providing researchers with never-before-seen views of what goes on deep within a living tumor. MGH scientists are using multiphoton laser scanning microscopy to visualize individual cells, allowing them to monitor gene expression, therapy effectiveness and interactions between tumor cells and normal cells. The work, published in this month’s Nature Medicine, demonstrates that the technique could be adapted to measure a wide range of physiological parameters.

Since the researchers use a living mouse model, they can perform a variety of experiments and take numerous measurements over time. "We can see what’s going on under the surface of the tumor without disturbing the tumor itself," says principal investigator Rakesh Jain, PhD, of MGH Radiation Oncology. Current imaging techniques do not have the same combination of depth and resolution. "This new technology gives us the ability to look deep inside the tissues of animals," says lead author Edward Brown, PhD, a post-doctoral fellow in Jain’s lab.

The MGH scientists first looked at gene expression at the tumor site, focusing on the angiogenesis-promoting gene VEGF. Cancer cells can coax nearby normal cells to produce VEGF, recruiting nourishing blood vessels to the tumor. By imaging individual cells in and around the tumor, the MGH team could see exactly which cells turned on the gene. They also could visualize blood vessels deep within a cancerous mass, with the expectation that this information will offer clues to the mechanism of tumor angiogenesis.

The scientists also were able to use their technique to track individual cell populations within a tumor. Some cancer cells develop a hardiness that allows them to survive in areas of very low oxygen. The MGH team could visualize these cells as they migrated to the center of the tumor mass, far away from oxygen-rich blood vessels. Since cancer therapies generally are administered through the bloodstream, these cells might also be inaccessible to conventional treatments. Jain says that innovative strategies may need to be devised to target these cells.