Intraoperative label-free multimodal nonlinear optical imaging of tumor microenvironments and extracellular vesicles

Nonlinear optical imaging;Tumor-associated extracellular vesicles;Intraoperative imaging;Tumor microenvironment

Sun, Yi ; Boppart ; Stephen A.

关键词: Nonlinear optical imaging;    Tumor-associated extracellular vesicles;    Intraoperative imaging;    Tumor microenvironment;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/99514/SUN-THESIS-2017.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

In recent years, various label-free nonlinear optical imaging techniques have been developed and applied in biomedical fields to provide unique imaging contrasts to biological tissues and act as promising noninvasive diagnostic tools in clinical tasks, like tumor margin determination. Especially, thanks to the advance of high-powered ultrafast pulsed lasers, integration and simultaneous acquisition of multiple nonlinear optical imaging modalities based on a single laser source have been made possible in the lab to generate real-time multi-contrast images of the ex vivo tumor microenvironment. While this simultaneous multimodal imaging system can acquire images that give insight into the tumor microenvironment, the lab-based nature restrains its application for more clinical studies because of the limited access to untreated fresh human tissue. This thesis reports the design, intraoperative operation, and promising results of a portable label-free multimodal nonlinear optical imaging system. By imaging untreated human breast tumor tissue immediately after surgical excision, the tumor microenvironment was visualized with high fidelity. The breast tumor subtypes as well as subtle tissue changes and activities such as desmoplastic reaction and apocrine metaplasia were recognized and validated by comparing with histology. In particular, tumor-associated extracellular vesicles (EVs), recently found to play essential roles in tumor progression, were identified and characterized in intraoperative multimodal nonlinear optical images before they experience any degradation, which is usually the case for human tissue imaged by lab-based multimodal nonlinear optical imaging systems due to tissue transportation. Quantification of EVs using intraoperative image data correlated well with pathological diagnoses like cancer invasiveness grade and closest tumor distance. This unique method of EV visualization provides new insights into tumor invasion in the microenvironment and may help achieve an innovative approach to cancer invasiveness determination and tumor margin assessment.