Label-Free System Images Molecular Features of Cancer Tissue in Real Time

A team at the University of Illinois at Urbana-Champaign has visualized the tumor microenvironment of human breast tissue shortly after it was surgically removed from a patient in the operating room, using a new portable optical imaging system developed by the team in the lab of professor Stephen Boppart. The system provided label-free optical contrasts of the tissue. These contrasts, correlated with histological findings, enabled point-of-procedure characterization of the tumor microenvironment. This intraoperative system could provide cancer researchers with a new tool for tracking tumor progression, and physicians with new technology for tissue pathology and diagnostics.

The imaging system uses precise light pulses to simultaneously image tissue in four modalities, enabling researchers and clinicians to study concurrent processes within the cells and tissue that make up the tumor microenvironment.

Label-free intraoperative nonlinear imaging of the tumor microenvironment provides real-time visualization of structural and molecular features, including extracellular vesicles that can be potential biomarkers of cancer aggressiveness. Courtesy of Biophotonics Imaging Laboratory, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign.

The team demonstrated the viability of its imaging system in the operating room at Carle Foundation Hospital in Urbana, Ill., during breast cancer surgeries. Within 30 minutes of the diseased tissue being extracted, the researchers were able to identify specific tissue features, including molecular signatures associated with metabolic activity inside individual cells that make up the tumor microenvironment.

The researchers were interested in measuring tumor-related extracellular vesicles (EVs), which are known to promote the spread of cancer. As part of their study, they collected and imaged healthy breast tissue that surgeons had removed from cancer-free patients during breast reduction procedures. When the researchers compared this healthy tissue with cancerous tissue, they found that the cancerous tissue exhibited increased EV densities.

“What we observed about the extracellular vesicles is significant, but it could only be accurately determined with our new system,” said researcher Yi Sun, noting how other portable optical imaging systems deployed in the operating room alter tissue samples either with fluorescent dyes or toxic ultraviolet light. “Our imaging technique works well with current cancer treatment routines and is free of any form of perturbation.”

The team’s future plans include using the imaging system on tissue specimens obtained from needle-biopsy procedures that are routinely performed in outpatient settings. The researchers will also continue to use the system on samples from the operating room.

Acquisition and interpretation of these intraoperative images not only provide real-time visualization of the tumor microenvironment but also offer the potential to use EVs as a label-free biomarker for cancer diagnosis and prognosis.

“We believe that capturing the dynamic cellular and molecular features in freshly removed or biopsied tissue specimens contains valuable diagnostic and prognostic information that is currently lost when specimens are placed in a fixative, and essentially killed quickly in order to preserve structure,” Boppart said. “Our imaging platform and methodology allow us to extract this new information in real time, at the point-of-procedure.”

The research was published in Science Advances (http://dx.doi.org/10.1126/sciadv.aau5603).