New research to bring Brillouin microscopy closer to widespread use in diagnostic medicine

Diagnostic imaging provides physicians and scientists with critical visual representations of the body’s internal structures, greatly enhancing clinical analysis and medical intervention. Researchers continue to break new ground on how various imaging technologies can provide a better understanding of human health.

Jitao Zhang, an assistant professor of biomedical engineering (BME) at Wayne State University and a scientific member of the Karmanos Cancer Institute’s Molecular Imaging Program, is an award-winning researcher who holds three patents for a new imaging technique called Brillouin microscopy that can map the cells and tissue stiffness that are often associated with early signs of such diseases as cancer and Alzheimer’s.

Different from conventional imaging methods such as confocal fluorescence microscopy, Brillouin microscopy can acquire the mechanical information (e.g. stiffness and viscosity) of biological samples in a non-contact and label-free manner.

His lab’s work to improve this method, which can answer many important questions in biophysics and mechanobiology, was featured in The Guardian after it was named by his peers in the scientific community as one of the 10 biggest science stories of 2022 .

Zhang and colleagues from the University of Maryland—where Zhang spent six years in the Department of Engineering before joining Wayne State in 2021—and the National Institutes of Health (NIH) recently published a research paper in Nature Methods examining the use of double-scanning Brillouin microscopy (dLSBM) to improve acquisition speed and reduce radiation doses, two major limiting factors for the widespread use of this technique in biomedicine.

“Existing confocal Brillouin microscopy is quite slow; it takes a few minutes to acquire a mechanical image of a single cell,” Zhang said. “If we’re imaging larger samples, like clumps of cancer cells or an early-stage embryo, we have to wait an hour or more to get an image.”

Using dLSBM, Zhang’s team reported speeds 50 to 100 times faster than the equivalent, while reducing the level of light radiation by 80 times for 2D and 3D mechanical mapping.

“With this innovation, we can obtain a mechanical image of cell clusters in minutes,” he said. “This improved acquisition speed is important because it allows us to probe details of cellular behaviors in near real time.”

Brillouin microscopy is an optical imaging method based on what is known as Brillouin Light scattering (BLS), first reported in 1922 by the French physicist Léon Brillouin. BLS occurs when light interacts with a substance and thermal fluctuations or vibrations of molecules in the material cause the light to scatter. Vibration can be affected by certain factors such as heat, compression, water content or material stiffness. It is the last of these features that is most valuable for the application of Brillouin microscopy as a diagnostic tool.

Disease progression, such as cancer metastasis, is often associated with changes in cell stiffness, but this is difficult to measure because cells are small and live in very soft tissue. Conventional techniques count prepared cells in a petri dish or other hard substrate. A Brillouin microscope uses only a laser beam to probe the mechanical properties, allowing measurement to be carried out when the cells are in their physiological conditions.

Since no physical contact is required, Brillouin technology is much less invasive and more convenient. Another application for which these features are important is to better understand fetal tissue development, particularly as it relates to diseases and disorders at birth.

“Due to the three-dimensional structure of an embryo, traditional contact-based techniques face great challenges for in vivo measurement,” Zhang said. “Since Brillouin microscopy works without contact, it sometimes becomes the only option available.”

Zhang collaborates with biologists and physicians at Karmanos and other institutions to address biomedical issues with technological innovations. However, Zhang noted that “Brillouin technology is still in its infancy and has limited imaging depth. Our lab will continue to work to make it more accessible to wider biomedical fields.”

The interaction between engineers and members of the medical community is especially critical in the diagnostic stage of the healthcare journey. Zhang and other Wayne State BME researchers are driving biomedical research and health care to unprecedented levels of advancement.