Design of an Endoscopic Raman Probe for Detection of Ovarian Cancer Elizabeth Kanter Matt Keller Vanderbilt University Advisor: Dr. Anita Mahadevan-Jansen VU BME

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

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

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

Current Detection Systems MethodProsCons Pelvic Exam Easy, Cheap, non-invasive Only discovers advanced disease Transvaginal ultrasonography Non-invasive, rapid test Not enough clinical trials to support CA 125 levels Minimally invasive, cheap Not reliable enough by itself for detection Biopsy Accurate diagnosis Invasive

Goals Gain comprehensive understanding of Raman spectroscopy and basic understanding of ovarian physiology Research design limitations imposed by laparoscope and physiological environment Come up with innovative Raman probe design to allow reliable, minimally invasive detection of ovarian cancer Implement design for clinical use

Raman Scattering 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 Plot of signal intensity vs. shift in wavenumber Very weak signal, compared to fluorescence Peaks narrow and highly specific to particular bonds (diff between normal & cancerous tissue)

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.

System Constraints for Our Probe 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

Our Probe Design

System Specifics Laser wavelength = 785 nm CaF 2 plano-cvx lenses, quartz bi-cvx lens ½ inch diameter optics Filter Transmission Curves:

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 $1500 for probe itself Save money on future health care costs through reliable early detection Unique

Current Work Completing parts orders AutoCAD drawing of probe IWB and designsafe

Future Work Build prototype Gather data with prototype to test design Make necessary adjustments Clinical trials

References Frank, C.J., Redd, D. C., Gansler, T.S, McCreedy, R.L. “Characterization of Human Breast Biopsy Specimens with Near- IR Raman Spectroscopy” Analytical Chemistry, 66, (1994) Mahadevan-Jansen, A., Raman Spectroscopy: From Bench top to Bedside. (2002) National Cancer Institute