Design of an Endoscopic Raman Probe for Detection of Ovarian Cancer

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Design of an Endoscopic Raman Probe for Detection of

Ovarian CancerElizabeth Kanter

Matt KellerVanderbilt University

Advisor: Dr. Anita Mahadevan-JansenVU BME

Developed for Dr. Paul King’s Senior Design Class

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

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

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

Method Pros Cons

Pelvic ExamEasy, Cheap, non-invasive

Only discovers advanced disease

Transvaginal ultrasonography

Non-invasive, rapid test

Not enough clinical trials to support

CA 125 levelsMinimally invasive, cheap

Not reliable enough by itself for detection

BiopsyAccurate diagnosis

Invasive

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)

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.

950 1050 1150 1250 1350 1450 1550 1650 1750 1850

Wavenumber (cm-1)

Adenocarcinoma

EndometriodCarcinoma

SerousCarcinoma

Normal

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

Our Probe Design

Spectrograph-CCD Source

Single fiber400 microns

Into the laparoscope

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

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

Future Goals

Extensive in vitro testing of probe

Refinement of component placement

Statistical comparisons with other previously proven probes

Eventually conduct clinical trials

References

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

Design of an Endoscopic Raman Probe for Detection of Ovarian Cancer

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