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Real-Time Tissue Imaging that Sees More

New microscope can visualize living tissue in real time and molecular detail, without any chemicals or dyes.

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Mary Bates, Contributor
Thu, 07/12/2018

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A new microscope system could enable real-time diagnostics and map the progression of diseases like cancer in living tissue, without the use of any chemicals or dyes. The technique, called simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy, is described in May in the journal Nature Communications.

“It’s high-quality, exciting work,” said Melissa Skala, a biomedical engineer at the Morgridge Institute for Research in Madison, Wisconsin, who was not involved in the study. “This paper is a nice combination of technology development and biological insights enabled by that technology.”

The methods scientists traditionally use for removing, processing and staining tissue to diagnose diseases are in some cases nearly a century old. A team led by Stephen Boppart, a professor of bioengineering and electrical and computer engineering at the University of Illinois at Urbana-Champaign, has developed a high-tech alternative: a new microscope system that can image living tissue in dynamic ways.

Unlike standard tissue pathology, SLAM microscopy is used on living tissue, even inside a living organism. Additionally, the technique uses only light, without the need for any dyes or chemicals that might negatively affect the function of cells. And while other stain-free imaging techniques have been developed, they usually only visualize a subset of cell activity. SLAM microscopy simultaneously collects multiple contrasts from cells and tissues, capturing molecular-level details and dynamics, such as metabolism.

Boppart and his colleagues developed a new type of laser, allowing them to perform multiple nonlinear optical imaging techniques at the same time. This results in perfectly co-registered images and data that can be used to extract functional, metabolic and structural properties of cells, tissues, and even extracellular vesicles in real time.

“We see this technology being useful wherever tissue is currently biopsied and viewed with standard histology,” said Boppart. “We can imagine using it at the point-of-procedure, such as after tissue biopsy or in the operating room to immediately assess tissue or cell function and health.”

In the recent study, Boppart’s team examined mammary tumors in rats along with the surrounding tissue environment -- structures that support tumors such as blood vessels, collagen, immune cells and extracellular vesicles. With SLAM microscopy, they were able to observe how different processes interacted as the tumors progressed. Boppart said the new technique provides a more comprehensive picture of the ever-evolving tumor microenvironment at a molecular and metabolic level in living tissue.

Skala said that although Boppart’s group demonstrated SLAM microscopy in oncology, she can imagine other uses.

“It could be used in surgical guidance or disease diagnostics. It could be incorporated into anything in which we’re developing microscopes for clinical or preclinical use,” she said.

Next, Boppart’s team is using SLAM microscopy to compare healthy and cancerous tissue in both rats and humans, with an eye on vesicle activity and how it relates to disease progression. They are also working to make portable versions of the SLAM microscope that could be used clinically.

Boppart believes that new imaging technologies like SLAM microscopy will change how researchers and clinicians visualize tissues and diagnose disease.

“SLAM can provide new label-free biomarkers or optical signatures for disease in real time, without sending samples or specimens to the pathology lab,” he said. “We are also discovering new processes and mechanisms in pathogenesis, such as basic processes in cancer cell function and activity.

“We think advances in microscopy such as this will change the way we detect, visualize and monitor diseases and ultimately will lead to better diagnosis, treatments and outcomes.”