Optical Imaging System Brings Molecular Diagnostics to the OR

A novel portable optical imaging system can successfully visualize the tumor microenvironment of excised human breast tissue, according to a new study.

Developed at the University of Illinois at Urbana-Champaign (UIUC; USA) and Carle Foundation Hospital (Urbana, IL, USA), the nonlinear imaging system uses precise light pulses to simultaneously image tissue in four modalities, showing concurrent molecular processes within cells and tissue in the tumor microenvironment. For example, collagen fibers appear in green; elastin fibers and Flavin-based cell cytoplasm appear in yellow; cell membranes, lipid boundaries, and extracellular vesicles (EVs) appear in magenta; and nicotinamide adenine dinucleotide in the cells and lipids appears in cyan.

To demonstrate the viability of the imaging system in the OR, the researchers intraoperatively imaged untreated human breast tissues from 29 patients with breast cancer using label-free optical contrasts, correlated with histological findings, which enabled point-of-procedure characterization of the tumor microenvironment within 30 minutes of diseased tissue extraction. EV densities were found to increase with higher histologic grade and shorter tumor-to-margin distance, and were significantly higher than those from seven cancer-free patients undergoing breast reduction surgery. The study was published on December 19, 2018, in Science Advances.

“EVs do play an essential role in cancer progression. Quantifying EV densities may be developed as a potential biomarker for future cancer diagnoses,” said lead author graduate student Yi Sun, MSc. “What we observed about the extracellular vesicles is significant, but it could only be accurately determined with our new system. Our imaging technique works well with current cancer treatment routines and is free of any form of perturbation.”

“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,” said senior author Professor Stephen Boppart, PhD, of the UIUC Beckman Institute for Advanced Science and Technology. “Our imaging platform and methodology allow us to extract this new information in real-time, at the point-of-procedure.”

Tumor-associated EVs play important roles in intercellular communication, both inside and outside of the tumor microenvironment, promoting tumor progression by directing cancer-associated events and changes. Various EV detection methods have been proposed and investigated, such as flow cytometry performed on circulating exosomes, immuno-based detection, and fluorescence label-based approaches for visualization, but none are label-free. Few attempts have been made to study human EVs using label-free imaging of fresh untreated or unstained human tumor tissues.

Related Links:
University of Illinois at Urbana-Champaign
Carle Foundation Hospital