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
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
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.
0
3.5
7
10.5
14
950 1050 1150 1250 1350 1450 1550 1650 1750 1850
Wavenumber (cm-1)
Inte
ns
ity
(%)
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
body
Our Probe Design
Spectrograph-CCD Source
Single fiber400 microns
Into the laparoscope
Spectrograph-CCD Source
Single fiber400 microns
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
