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Sci Adv. 2018 Dec 19;4(12):eaau5603. doi: 10.1126/sciadv.aau5603. eCollection 2018 Dec.

Intraoperative visualization of the tumor microenvironment and quantification of extracellular vesicles by label-free nonlinear imaging.

Author information

1
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
3
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
4
Carle Foundation Hospital, Urbana, IL 61801, USA.
5
Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
6
Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Abstract

Characterization of the tumor microenvironment, including extracellular vesicles (EVs), is important for understanding cancer progression. EV studies have traditionally been performed on dissociated cells, lacking spatial information. Since the distribution of EVs in the tumor microenvironment is associated with cellular function, there is a strong need for visualizing EVs in freshly resected tissues. We intraoperatively imaged untreated human breast tissues using a custom nonlinear imaging system. Label-free optical contrasts of the tissue, correlated with histological findings, enabled point-of-procedure characterization of the tumor microenvironment. EV densities from 29 patients with breast cancer were found to increase with higher histologic grade and shorter tumor-to-margin distance and were significantly higher than those from 7 cancer-free patients undergoing breast reduction surgery. 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.

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