Design of an Endoscopic Raman Probe for Detection of Ovarian Cancer

1. Design of an Endoscopic Raman Probe for Detection of Ovarian Cancer Elizabeth Kanter Matt Keller Vanderbilt University Advisor: Dr. Anita Mahadevan-Jansen VU BME Developed for Dr. Paul King’s Senior Design Class

2. The Problem: Ovarian Cancer • Deadliest of the gynecologic cancers • Fifth leading cause of cancer death among U.S. women • Occurs in 1 out of 57 women • An estimated 25,400 women will be diagnosed with the disease in 2003 • An estimated 14,300 American women will die from ovarian cancer in 2003 • Currently, 50 percent of the women diagnosed with ovarian cancer die from it within 5 years

3. The Problem: Ovarian Cancer • When detected before it has spread beyond the ovaries, more than 90 percent of women will survive longer than five years • Only 25 percent of ovarian cancer cases in the U.S. are diagnosed in the early stages • When diagnosed in advanced stages, the chance of five-year survival is only about 25 percent • Family history biggest risk factor: 3.6 times more likely to develop ovarian cancer if have primary relative afflicted

4. The Problem: Ovarian Cancer • When not diagnosed early, causes an additional health care cost of approximately $40,000 over a patient’s lifetime • May be difficult to diagnose because symptoms are easily confused with other diseases, and because there is no reliable, easy-to-administer screening tool

5. Current Detection Systems

6. Raman Scattering & Spectra • Photons collide inelastically with scattering molecule • Molecule enters virtual excited vibrational state, then returns to lower state • Photon of lower frequency re-emitted • Raman Spectrum is plot of signal intensity vs. shift in wavenumber • Very weak signal, compared to fluorescence • Peaks narrow and highly specific to particular bonds (how tell difference between normal & cancerous tissue)

7. Ovarian Raman Spectra The main peaks are protein peaks, located at 1450 cm-1, and another one at 1650 cm-1. The DNA peak is at 1330cm-1. In cancerous tissue, it is expected that the DNA peak has a greater magnitude compared to normal ovarian tissue. In cancerous tissue there is an increase in DNA because of large nuclei in the cells that comprise the tumor.

8. System Constraints • Must fit in microlaparoscopic tubing, which has internal diameter of < 3 mm • Must be able to visualize location of probe • Must read only the Raman signal • Must be in direct contact with tissue to read the Raman signal • Must not induce negative reaction in body

9. Our Probe Design

10. System Specifics • Laser wavelength = 785 nm • BP filter: 785 +/- 5 nm • LP filter: OD of 6 for wavelength < 790 nm • CaF2 lenses with 25 mm focal length • ½ inch (12.5 mm) diameter optics • 400-440 μm excitation fiber • 100-120 μm collection fiber bundle • Nitrogen-cooled CCD camera

11. Benefits of Our System • Minimally invasive – microlaparoscope only about 3 mm in diameter, so leaves no scar and can be done with local anesthetic • One-time cost for clinics – approximately $2100 plus labor for probe itself • Save money on future health care costs through reliable early detection • Unique

12. Future Goals • Extensive in vitro testing of probe • Refinement of component placement • Statistical comparisons with other previously proven probes • Eventually conduct clinical trials

13. References • Mahadevan-Jansen, A., Raman Spectroscopy: From Bench top to Bedside. (2002) • National Cancer Institute • http://www.ovariancancer.org/content/1-5-1.html • http://www.hcfinance.com/dec/dectside2.html