Rationale: Ovarian cancer, the most deadly female reproductive cancer, has a high death rate because there are very few symptoms in the early stages of the disease. Most cases are diagnosed at stages when the disease has spread, making it more difficult to treat or cure. Even though many advances have recently been made in drug treatment, surgery, and the understanding of the genetics of ovarian cancers, little has changed with respect to death rate. In fact, 70% of women who contract this cancer, die from it. Since the cancer is so deadly, and no effective screening method currently exists, women at high risk may elect to undergo prophylactic removal of their ovaries. However, the ovaries provide health benefits even in postmenopausal women, and removal of the ovaries can increase mortality in women under 45.

Objective: The objective of this research is to develop a miniature viewing device, called a falloposcope, which can be used to visualize the ovaries without requiring general anesthesia or cutting of tissue. The falloposcope will contain fiber optics to deliver light to the tissue and collect reflectance and fluorescence, using two techniques called multispectral fluorescence imaging (MFI) and optical coherence tomography (OCT). These techniques have been shown to successfully visualize cancers in many tissue types, more effectively than simple whitelight imaging.

Who will benefit? The initial target group is women at elevated risk for ovarian cancer (family or personal history of breast or ovarian cancer, certain gene mutations). These women might be counseled to undergo prophylactic removal of the ovaries, but as mentioned above, this procedure can have negative health consequences as well as the loss of fertility. Eventually, we hope to show that screening with our falloposcope is safe and effective enough to be used as a regular screening procedure for all women, such as is done now for mammography (breast cancer) or Pap smear (cervical cancer).

Clinical Applications: The falloposcope will be introduced through the vagina, uterus, and pass through the fallopian tubes to the ovary. The procedure is similar to a colonoscopy in that it requires sedation but not general anesthesia, and no tissue cutting is required. The desired benefits is that ovarian cancer could be caught early, when it is treatable, and that women at high risk might be able to delay or avoid having their ovaries removed. Also, because this endoscope images both the fallopian tubes and ovary, it will screen for two types of cancer. Some researchers believe that aggressive ovarian cancers may actually start in the fallopian tubes. The risks are that patients might react to the sedative, that the falloposcope might damage or perforate the reproductive tissue, that the falloposcope might not be sensitive enough to detect a cancer, or that the falloposcope might falsely indicate that a benign condition is cancer, leading to unnecessary further tests or removal of the ovaries.

Timeframe: At the successful conclusion of the proposed research, we will be ready to begin pilot clinical trials in women. These trials would start with women who are undergoing surgery to remove their reproductive organs anyway. Thus, we could determine if the device caused any damage and have gold standard histology to compute the accuracy of the falloposcope for diagnosis. Many years of large-scale testing and Food and Drug Administration approval would be required beyond this test period. Realistically, it would probably be 7-10 years from today, before this falloposcope was available to high risk women, and 5 years beyond that for all women.

Contribution of This Work: In this research, we will develop the falloposcope, showing that the extremely small size (0.6 mm diameter) is feasible, that it can produce images of high quality, and that the scope can be steered through a model of the female reproductive system. We will also test the ability of the endoscope to distinguish normal tissue from tissue that is cancerous, or tissue that is abnormal but not cancer (such as cysts, abnormal growth, or inflammation), using samples of tissue from surgeries. This research will advance both endoscope technology and the understanding of ovarian cancer detection.