Every year some 22,000 U.S. women are diagnosed with ovarian cancer, and more than 14,000 will die, according to the National Cancer Institute. Although the incidence –1 out of 72 women will develop ovarian cancer in her lifetime – appears less appalling than the 1 in 8 rate of breast cancer, ovarian cancer is the leading cause of gynecologic cancer deaths. The reason is that the cancer is rarely detected until it is at an advanced stage, when the chance of cure is poor.

“Only 25 percent of women can survive five years after the ovarian cancer is diagnosed,” says Bruce Wen, a medical physics graduate student at the University of Wisconsin-Madison, “because of the lack of an effective diagnostic screening technique.”

Wen is now proposing a research project that seeks to detect ovarian cancer at an early stage, when 72 to 91 percent of lives could be saved. By using a high-impulse laser, the new method will look deep into the biological network called the extracellular matrix that surrounds, supports and connects cells in human tissues; this matrix changes as cancer develops.

“This may be a promising way to provide early diagnosis of ovarian cancer.” Wen says.

Traditional ways to detect ovarian cancer include the blood test, ultrasound, or pelvic exam where a doctor explores the size, shape and position of the ovaries. These methods can only give information about the basic physical characteristics of a patient’s body, such as the general structure of a woman’s reproductive organs or a certain protein with greater concentrations in cancerous cells. Lacking a more specific and clear image of the cancerous tissue, traditional methods are not sensitive enough to discover ovarian cancer before the disease becomes life threatening.

The goal of Wen’s project is to build a detection tool that can image the tumor itself and the cellular-level environment of the epidermis of the ovary, the outer layer of the ovary’s skin where about 90 percent of ovarian cancer occurs.

“There is a compelling need for new technology that can map malignant ovarian tumor…with a good resolution and sensitivity,” Wen writes in his research proposal.

A major tool for Wen’s efforts is a microscope using the Second Harmonic Generation technique, which can capture the composition of the extracellular matrix on the epidermis with a high resolution. The matrix, which mainly consists of the collagens, is the part of human tissue outside the cells that provides structural support to the cells and connects them together.

Studies have shown that the structure and density of the matrix change as some cancers, including ovarian cancer, progress. From the lens of the Second Harmonic Generation microscope, the collagen assembly of a healthy tissue’s matrix looks like a tangled mess pointing at thousands of directions, while that of a cancerous or high-risk tissue appears highly ordered. Wen presumes this orderly configuration may act as a bridge that facilitates the cancer’s spread.

SHG microscope showing the collagen assembly in cancer (left), high risk (middle) and healthy (right) tissues Image from Wen's research proposal
SHG microscope showing the collagen assembly in cancer (left), high risk (middle) and healthy (right) tissues
Image from Wen’s research proposal

Previously Wen’s lab scanned the epidermis of ovaries with a laser and used another microscope to examine the transmission of photons, the particles that make up the laser light, inside the tissues. Results showed that the photons’ transmissions vary among healthy, high-risk and cancerous tissues, suggesting potential differences in these tissues’ interior configurations. Now with the Second Harmonic Generation microscope, researchers can accurately take images of these differences by observing the collagen assemblies of the extracellular matrix in the tissues.

In this way, future clinical practices can look for ovarian cancer at multiple scales. First, doctors can have a quick screening over the epidermis of ovaries to find any abnormities by using a laser scanner using the Optical Coherence Tomography (OCT) technique, which has been widely used to explain the photons’ scattering properties inside a tissue. Then they can examine the particular abnormal areas at the cellular scale with the Second Harmonic Generation microscope.

“This combination of multi-scale measurements is the primary innovation of our research,” says Wen.

Directed by his advisor, Paul Campagnola, an associate professor at the Department of Medical Physics, UW-Madison, Wen has been studying more than 300 ovarian tissues, trying to build up a library that classifies the images of cancerous, high-risk and healthy tissues. Based on these resources, he expects this new technology to be developed in early 2014. The next step would be producing such devices for clinical use.

Once mature, this technology can also be able to detect other tumors that occur on the epidermis of a tissue, such as skin cancer and prostate cancer, as well as diseases that correlate with the changes of the extracellular matrix environment, like asthma.

“Researchers need to develop an early detection test for ovarian cancer,” the U.S. Ovarian Cancer National Alliance website advises. If successful, Wen’s project will be exciting news to the 22,000 women diagnosed with ovarian cancer every year.

“I find this research very meaningful,” says Wen. “It’s a life-saving cause.”