1. Design of an Endoscopic Raman Probe for the Detection of Ovarian Cancer Elizabeth Kanter, Matthew Keller Dr. Anita Mahadevan-Jansen Designed as part of BME Senior Design (Instructor: Dr. Paul King) Vanderbilt University

2. The Problem: Ovarian Cancer uFifth leading cause of cancer death among U.S. women uAn estimated 25,400 U.S. women will be diagnosed with the disease, and an estimated 14,300 will die from it, in 2003 uCurrently, 50 percent of the women diagnosed with ovarian cancer die from it within 5 years u3.6 times more likely to develop ovarian cancer if have primary relative afflicted Source: National Cancer Institute and http://www.ovariancancer.org/content/1-5-1.html

3. The Problem: Ovarian Cancer uWhen detected before it has spread beyond the ovaries, there is a greater than 90 percent five- year survival rate uLate-stage diagnosis, which occurs in 75% of cases, causes an additional health care cost of approximately $40,000 over a patient’s lifetime uDifficult to diagnose because it is often asymptomatic, any symptoms present are easily confused with other diseases Source: National Cancer Institute and http://www.hcfinance.com/dec/dectside2.html

4. 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 efficacy CA 125 levels Minimally invasive, cheap Not reliable enough by itself for detection BiopsyAccurate diagnosisInvasive

5. Motivation uThere is currently no reliable, easily administered method for early detection of ovarian cancer uOptical spectroscopy has been proven to be effective as a real-time, non-intrusive, automated diagnostic tool for several physiological systems: vColon, cervix, skin, esophagus uRaman spectroscopy has been shown to quickly give accurate biochemical information necessary to diagnose cancer Source: Mahadevan-Jansen (2002)

6. Raman Scattering & Spectra uPhotons collide inelastically with scattering molecule uMolecule enters virtual excited vibrational state, then returns to lower state uPhoton of lower frequency re-emitted uRaman Spectrum is plot of signal intensity vs. shift in wavenumber (1/wavelength) uVery weak signal, compared to fluorescence uPeaks narrow and highly specific to particular chemical bonds, which allows differentiation between normal & cancerous tissue

7. Overall System Scheme u785 nm diode laser uFused-silica low –OH fiber uCooled CCD camera uSignal processing software

8. Ovarian Raman Spectra uProtein peaks are located at 1450 cm -1 and 1650 cm -1 uA DNA peak is located at 1330 cm -1. uBoth protein and DNA peaks are increased in magnitude in cancerous tissue due to enlarged nuclei

9. Probe Constraints The in vivo Raman probe to be designed should uFit inside the microlaparoscope, which has an inner diameter < 3 mm uBe able to visualize location of probe tip uRead only the Raman signal of tissue uBe in direct contact with tissue during each measurement uNot induce a harmful reaction in the body

10. Probe Design u½ inch (12.7 mm) diameter optics uBandpass filter: 785 +/- 5 nm uLongpass filter: OD of 6 for wavelength < 790 nm uCaF 2 lenses u400 μm core excitation fibers u100 μm core collection fiber bundle with 11 fibers

11. Probe Testing (above) The probe being tested in the lab for the first time (below) The first spectrum taken with the developed Raman probe

12. Benefits of Our System uOne-time cost for clinics – approximately $2100 plus labor for probe itself uSave money on future health care costs through reliable early detection uUnique u Minimally invasive – microlaparoscope < 3 mm in diameter, so leaves no scar and can be done with local anesthetic

13. Future Goals uReplacement of wrong lens and realignment uExtensive in vitro testing of probe uStatistical comparisons with other previously proven probes for analogous procedures uEventually conduct clinical trials, although perhaps with a later generation model