The microscope system images living tissue without the need for chemicals or dyes. The technique, called simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy, uses precisely tailored pulses of light to simultaneously image with multiple wavelengths. Using light helps cancer researchers study concurrent processes in cells and tissue to create a new tool for tracking tumor progression and allowing physicians to use it for tissue pathology and diagnostics.
“The way we have been removing, processing and staining tissue for diagnosing diseases has been practiced the same way for over a century,” said Dr. Stephen Boppart, the study’s leader who is a medical doctor and bioengineering and electrical and computer engineering professor at the university. “With advances in microscopy techniques such as ours, we hope to change the way we detect, visualize and monitor diseases that will lead to better diagnosis, treatments and outcomes.”
SLAM microscopy is different from other standard tissue pathology for a number of reasons. It can be used on living tissue inside of a living being, which means it could be used for clinical diagnosis or to guide surgery in an operating room. It also uses no dyes or chemicals and only light. Standard tissue pathology includes removing a tissue sample and using chemical stains, creating a time-consuming process while also potentially disrupting cells.
There are currently other stain-free imaging techniques available, but the researchers suggest that those methods only visualize some signals and measure specific biological or metabolic signatures. SLAM microscopy is able to collect multiple contrasts from cells and tissues to capture molecular-level details and dynamics like metabolism.
The researchers studied SLAM microscopy by looking at mammary tumors in rats, as well as the surrounding tissues. The data showed that they could see the range of dynamics as the tumors progressed and could see how different processes interacted.
“We known the tumor is there, but tumors support a whole ecosystem in the tissue,” Sixian You, the first author of the paper, said. “They recruit healthy cells to support them. SLAM allows us to have a comprehensive picture of this ever-evolving tumor microenvironment at subcellular, molecular and metabolic levels in living animals and human tissue. Monitoring that process can help us better understand cancer progression, and in the future could lead to better diagnosis of how advanced a tumor is, and better therapeutic approaches aimed at halting the progression.”
The researchers also noted that the cells near the tumors had differences in metabolism and morphology, which meant that the cells had been levied by the cancer. The also found that surrounding tissues made infrastructure to support the tumor and communication between the tumor cells and the surrounding cells in vesicles.
“Previous work has shown that tumor cells release vesicles to lure the surrounding cells to support them,” You said. “Then the cells that have been recruiting release their own vesicles to go back to the tumor. It’s a vicious cycle. It’s very different from the activity we see in our control samples with healthy tissue. The capability to see the dynamics of all these important player in authentic tumor environments can help shed light on this mysterious but critical process.”
The University of Illinois researchers plan to use SLAM microscopy to compare healthy tissue and cancer tissue in rats and humans to focus on vesicle activity and how it relates to cancer aggressiveness. They are also working on making a portable version of the technique to use clinically.
“There is a wealth of new data, information and biomarkers in the images we collect from fresh tissue that is still metabolically active, or in living organisms, where we can visualize the dynamics of individual cells and their collective behaviors,” Boppart said. “These, we expect, will become new markers for diseases such as cancer, and our imaging technology will help detect these for disease screening, diagnostics and monitoring applications. We believe that this technology will open the possibility of complementing, or even replacing, standard histopathology processing, which is time- and labor-intensive and can only be done on removed, fixed, dead tissue.”
The research was published in the journal Nature Communications and was funded by the National Institutes of Health and a McGinnis Fellowship.