Simultaneous optical coherence tomography and laser induced fluorescence imaging in rat model of ovarian carcinogenesis

Abstract

Determining if an ovarian mass is benign or malignant is an ongoing clinical challenge. The development of reliable animal models provides means to evaluate new diagnostic tools to more accurately determine if an ovary has benign or malignant features. Although sex cord-stromal tumors (SCST) account for 0.1–0.5% of ovarian malignancies, they have similar appearances to more aggressive epithelial cancers and can serve as a prototype for developing better diagnostic methods for ovarian cancer. Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy are non-destructive optical imaging modalities. OCT provides architectural cross-sectional images at near histological resolutions and LIF provides biochemical information. We utilize combined OCT-LIF to image ovaries in post-menopausal ovarian carcinogenesis rat models, evaluating normal cyclic, acyclic and neoplastic ovaries. Eighty-three female Fisher rats were exposed to combinations of control sesame oil, 4-vinyl cyclohexene diepoxide (VCD) to induce ovarian failure,and/or 7,12-dimethylbenz[a]anthracene (DMBA) to induce carcinogenesis. Three or five months post-treatment, 162 ovaries were harvested and imaged with OCT-LIF: 40 cyclic, 105 acyclic and 17 SCST. OCT identified various follicle stages,corpora lutea (CL), CL remnants, epithelial invaginations/inclusions and allowed for characterization of both cystic and solid SCST. Signal attenuation comparisons between CL and solid SCST revealed statistically significant increases in attenuation among CL. LIF characterized spectral differences in cyclic, acyclic and neoplastic ovaries attributed to collagen, NADH/FAD and hemoglobin absorption. We present combined OCT-LIF imaging in a rat ovarian carcinogenesis model, providing preliminary criteria for normal cyclic, acyclic and SCST ovaries which support the potential of OCT-LIF for ovarian imaging.

Figure 1

Cyclic ovary. (A) OCT image of cyclic Con/Con ovary and (B) corresponding histology. G, Graafian follicle; CL, corpus luteum; arrow, CL remnants and intervening collagen; asterisk, vascular spaces. OCT image and histology are to scale. Scale bar: 500 µm.

Figure 2

Acyclic ovary. (A) OCT image of acyclic VCD/Con ovary and (B) corresponding histology. (C) OCT image of cyclic Con/DMBA ovary and (D) corresponding histology. (E) Magnification of Figure 2A acyclic VCD/Con ovary and (F) corresponding magnified histology. S, stroma; DF, degenerating follicles; SF, secondary follicle; F, infiltrating fat; CL, corpus luteum with cyst; arrow, epithelial invagination; asterisk, vascular spaces. OCT image and histology are to scale. Scale bar: 500 µm.

Figure 3

Solid SCST. (A) OCT image of ovary with solid SCST and (B) corresponding histology. SCST, sex cord-stromal tumor; arrow, collagenous capsule; asterisk, vascular spaces. (C) OCT image of solid SCST within benign cyst and (D) corresponding histology. SCST, sex cord-stromal tumor; arrow, benign cyst lining; C, adjacent benign cyst. OCT image and histology are to scale. Scale bar: 500 µm.

Figure 4

Solid SCST with cystic component and cystic SCST. (A) OCT image of ovary with solid SCST with cystic component and (B) corresponding histology. SCST, Sex cord-stromal tumor; CT, cystic component of SCST; C, adjacent benign cyst (ruptured in histopathology). (C) OCT image of ovary with cystic SCST and (D) corresponding histology. MT, malignant tubules in stroma; P, papillation; arrows, benign cyst lining; asterisk, vascular spaces. OCT image and histology are to scale. Scale bar: 500 µm.

Figure 5

LIF spectral curves. (A) Solid tissue spectral curves. (B) Cystic tissue spectral curves. (C) Scatterplot of the ratio of 390 nm to 450 nm fluorescence emission compared among solid regions of ConCon normal cycling ovaries and solid SCST. Using a cut-off of 0.7 AU (black bar), a sensitivity of 88% to SCST and a specificity of 60% to normal cycling ovaries is achieved. AU: Arbitrary units. No.: Number.