Detection of Early Ovarian Tumor Associated Neo-Angiogenesis by Contrast-Enhanced Ultrasound in Laying Hens, a Spontaneous Animal Model of Human Ovarian Cancer
Objective: Tumor associated neo-angiogenesis (TAN) is an early event in tumor development and a target for early detection of cancer. It is difficult to detect TAN by traditional ultrasound and identify patients at early stage ovarian cancer (OVCA). Laying hens develop OVCA spontaneously with histopathology identical to humans. This can be detected by transvaginal ultrasound (Barua et al., 2007). The goal of this study was to detect TAN during early stage OVCA by Contrast enhanced ultrasound (CEUS) imaging in laying hens.
Methods: White Leghorn laying hens (3 years old) were scanned transvaginally before, during and after injection with the ultrasound contrast agent (UCA) OptisonTM. Gray scale ovarian morphology, Doppler indices and UCA parameters were imaged and recorded. Hens were sacrificed following scans and ovaries were evaluated by gross and histology. Expression of vascular endothelial growth factor (VEGF) was determined by immunohistochemistry.
Results: OptisonTM enhanced overall visualization of ovarian vascularity. In tumor-containing ovaries, visualization of vascular areas was increased significantly by OptisonTM. Achievement of peak intensity was faster and OptisonTM wash-out was slower than in normal ovaries. No differences were observed in these parameters between early stage and late stage OVCA. VEGF expression was higher in hens predicted to have ovarian TAN by CEUS.
Conclusion: The results of this study suggest that laying hens may be an excellent model to study the kinetics of UCA associated with early stage OVCA and form the foundation for clinical studies to establish a non-invasive early detection tool for OVCA.
Acknowledgment: Prevent Cancer Foundation (A.B.).