Development of contrast enhanced ultrasonography using the sheep ovarian model of microvascular regulation

A large number of diseases, including cancer, infertility, heart and pregnancy abnormalities, depend on changes to the blood flow in the area of the disease. In cancer generally there is more blood flow generated by the cancer cells, while in heart attacks there is an area in the heart that almost has no blood supply. The seriousness of the disease is also linked to small blood flow changes. The ovary is a tissue where blood flow changes occur naturally during the menstrual cycle. Thus this tissue can simulate a range of diseases and can be used as a system for setting up an accurate blood flow measuring tool. Ultrasound imaging combined with contrast agents that are injected into the blood stream to assess the blood supply of small areas, would be a major advance in the diagnosis and treatment of many different diseases. We plan to develop the tools to do this by focussing on a small tissue in which the blood supply changes from very small to very large in a predictable reproducible way. We can also use drugs to change the blood supply to this tissue. This tissue is in the sheep ovary and if we can use this to create tools to measure normal and abnormal blood flow we can then take this tool directly into the clinic to measure the important changes to blood flow in a variety of important human diseases.

The ability for the real-time detection and monitoring of microvascular tissue perfusion would be a major advance in the detection of pelvic pathology. In addition microvascular changes are central to a wide range of diseases such as inflammation, cancer and cardiovascular disease. Although blood flow can be measured in large vessels, the measurement of capillary flow is its infancy. This research aims to use the ovine ovary model of angiogenesis and its manipulation to develop and refine contrast enhanced ultrasonography of the microvasculature for future use in the clinic. Microbubble enhanced sonography will be developed using the ovine corpus luteum, the structure in the body with the most marked microvascular circulation. This gland undergoes predictable phases of marked angiogenesis and vascular regression, representing a minimal and maximal perfusion, and the vascular development can be manipulated in vivo. Quantitative microvascular assessment will be performed initially on the normal as well as the chemically regressed ovary, and will lead to the development of an intravaginal probe for real-time ovarian contrast imaging. The results will be compared with endocrinological and histological data. A 3D perfusion imaging technique will be finally developed as means of an objective real time histology tool. The research will translate into clinical diagnostic applications during pelvic sonography for the detection of abnormal microvascular networks such as seen in endometriosis, adenomyosis, pelvic inflammatory disease and ectopic pregnancy.