By Deborah Borfitz
March 29, 2022 | Biology and technology have finally advanced to the point where a teentsy device for imaging the inside of the fallopian tubes is recognized both as an unmet clinical need and a plausible engineering feat. Introducing the falloposcope, intended to search for signs of early-stage ovarian cancer and currently undergoing pilot testing in volunteers having their tubes removed for reasons other than cancer to establish a baseline for normal.
Sharing the news is lead device developer Jennifer Barton, biomedical engineering professor at the University of Arizona and director of UArizona’s BIO5 Institute. It wasn’t until around 2016 that it was first hypothesized that ovarian cancer originates in the cells in the fallopian tubes and metastasizes to the ovaries over the course of six to seven years.
“So, that answered the question of why we never saw early ovarian cancer… we were looking in the wrong place,” she says. More than three-fourths of ovarian cancer cases are not found until the cancer is in an advanced stage.
Around the same time, the flexible and biocompatible components were becoming commercially available for building a high-capability device that could navigate ducts no wider than a sewing needle. Even then, industry collaborators had to push past their limits to manufacture an assortment of custom lenses, tubing, ferrules, fibers, and fiber-optic products, she says.
Aside from outside companies, academic collaborators on the falloposcope include experts in cancer biology, physiology, and clinical obstetrics and gynecology, Barton continues. Since 2018, the work has been funded by the U.S. Army, which administers grants for an ovarian cancer research program run by the Department of Defense.
At 0.8 millimeters in diameter, the falloposcope's small size and high resolution are unprecedented. “It’s itty bitty," says Barton, who also holds appointments in optical sciences and medical imaging and is a member of the UArizona Cancer Center.
The falloposcope uniquely combines three optical imaging techniques: fluorescence imaging to examine metabolic and functional changes in tissue, optical coherence tomography to observe structural changes, and white light reflectance imaging to gather information about the tissue. Overall, imaging of the fallopian tubes has been limited, says Barton, although low-resolution white light imaging was being done back in the 1990s to look for blockages or other potential causes of infertility.
As employed here, the tissue reflects some wavelengths of light more strongly than others and provides information on the quantity of molecules like hemoglobin, she explains. Fluorescence imaging provides information about the health of the tissue on a large scale, and optical coherence tomography then zooms in to get a beneath-the-surface view of any parts that look suspicious (e.g., tissue thickening).
A 2020 article in Translational Biophotonics (DOI: 10.1002/tbio.202000011) provides a full description of the falloposcope.
In Vivo Testing
The principal investigator for the pilot study currently underway is John Heusinkveld, M.D., a specialist in female pelvic medicine and reconstructive surgery at Banner – University Medical Center Tucson. Use of the falloposcope on women already having their tubes removed is a safe starting point for in vivo testing, says Barton, noting the procedure has a “nonsignificant risk” designation from the U.S. Food and Drug Administration (FDA). “That basically means the FDA has delegated [oversight] authority back to the University of Arizona’s Human Subjects Protection Program.”
The only risk to study volunteers is “a little bit of extra time added to their surgery while we image,” she says. “All indications are that we won’t cause any damage.”
A secondary reason for enrolling women scheduled for surgery is that the healthy state of their fallopian tubes can be histologically confirmed. Researchers hope to capture the full “variety of normal” across a diverse set of women.
As of September, Heusinkveld has successfully used the falloposcope in four volunteers. The plan is to image 20 sets of fallopian tubes by the end of this summer, says Barton, and at least initially these will all be his patients.
The University of Arizona Institutional Review Board approved the enrollment of anyone coming in for a cervical dilation and removal of their fallopian tubes, she says. “We are indebted to these volunteers who are so eager to help us and be engaged in this type of study.”
Heusinkveld has been involved in every step of development of the falloposcope, notably usability testing (e.g., if it is paired with the right hysteroscope and has the right flexibility and handle positioning), Barton continues. His initial training on the device happened during testing in pig tissue and excised human tissue, and his input during the pilot study will determine how it might be further refined for clinical use.
Screening Test Potential
The imagined user of the falloposcope, at least initially, would be a physician specialist working in an outpatient setting. “We’d like this to be kind of like a colonoscopy, without the prep,” says Barton.
Yet to be decided is if the screening test would require sedation or any sort of local anesthesia, she adds. In an ideal world, the falloposcope would one day be so easy to use that it could be in the preventive toolbox of general practitioners.
Primary targets for screening would be women at high risk for ovarian cancer, including predisposed individuals based on genetic markers or family history, says Barton. Many such women are currently opting for prophylactic removal of their ovaries and fallopian tubes, called salpingo-oophorectomy, and “that has consequences at any age, particularly if the woman is pre-menopausal or still wishes to bear children.”
Patients who have their ovaries removed at a young age may need to be placed on supplemental hormones, Barton says. A significant percentage never feel as good as they once did.
The idea here is to give at-risk women another option to discuss with their physician, she says. If women start coming in for regular screenings to ensure everything looks normal, fewer of them will be getting risk-reducing surgeries they don’t in fact need—or at least delay having it until after their childbearing years.
The odds that these high-risk women have a serous tubal intraepithelial carcinoma, a malignant lesion with metastatic potential, is only between 5% and 10%, she notes.
The research team now has the funding to begin actively planning for their next step, which is a five-year study where they will image the fallopian tubes of women opting to undergo salpingo-oophorectomy, Barton shares. That will help gauge the detection sensitivity and specificity of the falloposcope for this type of cancer.
At that point, the University of Arizona will seek to license the technology to a medical device company to usher the falloposcope to market as a preventive screen through the FDA approval process. Tech Launch Arizona, UArizona’s technology transfer office, patented the technology and is orchestrating those dialogues.