A significant challenge in detecting cervical pre-cancer in low-resource settings is the lack of effective screening
facilities and trained personnel to detect the disease before it is advanced. Light based technologies, particularly
quantitative optical spectroscopy, have the potential to provide an effective, low cost, and portable solution for cervical
pre-cancer screening in these communities. We have developed and characterized a portable USB-powered optical
spectroscopic system to quantify total hemoglobin content, hemoglobin saturation, and reduced scattering coefficient of
cervical tissue in vivo. The system consists of a high-power LED as light source, a bifurcated fiber optic assembly, and
two USB spectrometers for sample and calibration spectra acquisitions. The system was subsequently tested in Leogane,
Haiti, where diffuse reflectance spectra from 33 colposcopically normal sites in 21 patients were acquired. Two different
calibration methods, i.e., a post-study diffuse reflectance standard measurement and a real time self-calibration channel
were studied. Our results suggest that a self-calibration channel enabled more accurate extraction of scattering contrast
through simultaneous real-time correction of intensity drifts in the system. A self-calibration system also minimizes
operator bias and required training. Hence, future contact spectroscopy or imaging systems should incorporate a selfcalibration
channel to reliably extract scattering contrast.
KEYWORDS: Tissues, Optical spectroscopy, Cervix, Biopsy, Cervical cancer, Visible radiation, In vivo imaging, Absorption, Tissue optics, Monte Carlo methods
Neovascularization in cervical intraepithelial neoplasia (CIN) is studied because it is the precursor to the third most common female cancer worldwide. Diffuse reflectance from 450-600 nm was collected from 46 patients (76 sites) undergoing colposcopy at Duke University Medical Center. Total hemoglobin, derived using an inverse Monte Carlo model, significantly increased in CIN 2+ (N=12) versus CIN 1 (N=16) and normal tissues (N=48) combined with P<0.004. Immunohistochemistry using monoclonal anti-CD34 was used to quantify microvessel density to validate the increased hemoglobin content. Biopsies from 51 sites were stained, and up to three hot spots per slide were selected for microvessel quantification by two observers. Similar to the optical study results, microvessel density was significantly increased in CIN 2+ (N=16) versus CIN 1 (N=21) and normal tissue (N=14) combined with P<0.007. Total vessel density, however, was not significantly associated with dysplastic grade. Hence, our quantitative optical spectroscopy system is primarily sensitive to dysplastic neovascularization immediately beneath the basement membrane, with minimal confounding from vascularity inherent in the normal stromal environment. This tool could have potential for in vivo applications in screening for cervical cancer, prognostics, and monitoring of antiangiogenic effects in chemoprevention therapies.
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