Cervical cancer is the second most common female cancer worldwide. The ability to quantify physiological and morphological changes in the cervix is not only useful in the diagnosis of cervical precancers but also important in aiding the design of cost-effective detection systems for use in developing countries that lack well-established screening and diagnostic programs. We assessed the capability of a diffuse reflectance spectroscopy technique to identify contrasts in optical biomarkers that vary with different grades of cervical intraepithelial neoplasia (CIN) from normal cervical tissues. The technology consists of an optical probe and an instrument (with broadband light source, dispersive element, and detector), and a Monte Carlo algorithm to extract optical biomarker contributions including total hemoglobin (Hb) concentration, Hb saturation, and reduced scattering coefficient from the measured spectra. Among 38 patients and 89 sites examined, 46 squamous normal sites, 18 CIN 1, and 15 CIN 2(+) sites were included in the analysis. Total Hb was statistically higher in CIN 2(+) (18.3 +/- 3.6 microM, mean +/- SE) compared with normal (9.58 +/- 1.91 microM) and CIN 1 (12.8 +/- 2.6 microM), whereas scattering was significantly reduced in CIN 1 (8.3 +/- 0.8 cm(-1)) and CIN 2(+) (8.6 +/- 1.0 cm(-1)) compared with normal (10.2 +/- 1.1 cm(-1)). Hemoglobin saturation was not significantly altered in CIN 2(+) compared with normal and CIN 1. The difference in total Hb is likely because of stromal angiogenesis, whereas decreased scattering can be attributed to breakdown of collagen network in the cervical stroma.
A retrospective review of the transvaginal sonograms of 50 women with laparoscopically confirmed ectopic pregnancy was performed to determine whether certain sonographic findings can be detected to confirm the diagnosis. Forty-seven of the 50 pregnancies were tubal. A tubal ring (a 1-3-cm mass consisting of a 2-4-mm concentric, echogenic rim of tissue surrounding a hypoechoic center) was seen in 23 of 34 (68%) ectopic pregnancies in which the fallopian tube had not ruptured, and the tubal ring could be distinguished from a corpus luteum cyst in most cases. Transvaginal sonography also depicted simple (n = 22) or particulate (bloody) (n = 13) peritoneal fluid associated with ectopic pregnancy. In each case in the series, at least one abnormal uterine, adnexal, or peritoneal finding was detected at transvaginal sonography. Because of its improved resolution of uterine and adnexal structures, transvaginal sonography is recommended as a means for detailed evaluation of patients suspected of having an ectopic pregnancy.
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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