When someone has Fabry disease, a rare genetic disorder, certain fatty substances called lipids build up in their heart, kidneys, and other organs over time, causing serious health problems. For years, doctors have known this happens, but they couldn't see exactly where in the tissue these harmful buildups occur—until now.
Researchers at the Leibniz-Institut für Analytische Wissenschaften—ISAS in Dortmund, Germany, have developed a powerful new imaging technique that maps lipids in heart tissue with incredible detail. For the first time, they combined two different microscopy methods—Raman microscopy and AP-MALDI mass spectrometry imaging—to create a molecular map of tissue at the cellular and subcellular level. Their work was published in the journal Analytical Chemistry.
"Only by combining Raman microscopy with mass spectrometry imaging is it possible to obtain a comprehensive picture of the molecular processes within the tissue," said Professor Dr. Sven Heiles, who led the research. "For a reliable diagnostic assessment, it's important to know exactly where in the tissue Gb3 molecules accumulate."
The team tested their technique on heart tissue from mice with Fabry disease. In this condition, lipids called globotriaosylceramides ( Gb3, for short) aren't broken down properly by the body and accumulate in organs. The new imaging revealed something surprising: instead of spreading evenly, different forms of Gb3 created tiny, precisely defined clusters scattered throughout the heart tissue. This uneven pattern had never been seen so clearly before.
Professor Dr. Kristina Lorenz, who also worked on the study, explained that while scientists understood the genetic cause of Fabry disease and knew which organs were affected, they had limited knowledge about how lipids distribute within human tissue at the cellular level. "These new findings could help us better understand the course of the disease in the future," she said.
The imaging achieved remarkable precision—the Raman microscope could see details as small as 2 micrometers across (a micrometer is one-thousandth of a millimeter), while the mass spectrometry imaging pinpointed molecules in areas as small as 5 micrometers. The researchers developed special software to merge both datasets and align them perfectly on the same tissue sample.
The next step is to apply this technique to tissue samples from actual Fabry disease patients. The team hopes that by understanding exactly where and how lipids accumulate in individuals, doctors could someday diagnose the disease earlier and tailor treatments more effectively. The method may also help scientists studying other conditions involving lipid changes, such as cardiovascular and metabolic diseases.
In short, scientists now have a new tool to watch diseases unfold at the smallest scale—and that could change how doctors detect and treat illnesses like Fabry disease in the future.