Two-photon excited fluorescence imaging is useful for identifying ovarian tumors in mice

I work at the University of Arizona in the Tissue Optics Lab, led by Dr. Jennifer K. Barton. Our lab focuses on developing and using optical imaging methods for disease detection and monitoring. We are particularly interested in obtaining better understanding of the progression of colon and ovarian cancer. My main area of study has been using optical imaging methods to detect ovarian cancer development in a mouse model of ovarian cancer.

In a recent study using two-photon excited fluorescence (TPEF) microscopy for imaging mouse ovarian tumors, we discovered large changes in endogenous fluorescence during tumor development.¹ For this study we used a mouse model consisting of dosing with 4-vinylcyclohexene diepoxide and/or 7, 12—dimethylbenz[a]anthracene and/or sesame oil vehicle only, resulting in a variety of tumor types. Two of the most interesting tumor types that developed were tubular hyperplasia, which occurred in nearly all VCD-dosed animals, and adenocarcinoma, which occurred in some VCD and DMBA combination-dosed animals. Both tubular hyperplasia and adenocarcinoma had a trend toward larger stromal cells (in some areas), as compared to normal. Additionally, the large stromal cells contained extremely brightly fluorescing material, which we identified as lipofuscin, a lipopigment that is known to accumulate with age in some organs. Representative TPEF images of ovaries from age matched animals diagnosed as normal, tubular hyperplasia, and adenocarcinoma are shown in the figure below.

TPEF images (maximum intensity projections) from ovaries diagnosed as a) normal, b) tubular hyperplasia, and c) adenocarcinoma show an increase in the size of cells containing lipofuscin in tumors.

We were very excited to see the obvious changes in cell morphology and the unexpected large increases in lipofuscin accumulation in diseased ovaries. Since the completion of this study, we have conducted an in vivo imaging study, using the same animal model, which allowed us to watch the progression of cellular changes from before to after DMBA dosing. We hope to be able to determine the earliest time point during tumor development that these changes are visible.

REFERENCE
1. J. Watson et al., Lasers Surg. Med., 45, 3, 155–166 (2013).

JENNIFER WATSON is a PhD candidate in Biomedical Engineering at the University of Arizona (Tucson, AZ) under the advisement of Dr. Jennifer K. Barton. Her research interest is using optical imaging for cancer detection.