In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker.
A quantitative measure of intraepithelial neoplasia which can be made in vivo without the need for tissue removal would be of clinical significance. Our group is working to develop such a technique based on fluorescence spectroscopy. This paper reviews the use of fluorescence spectroscopy for tissue diagnosis, describes our work to apply this technique to the diagnosis of cervical intraepithelial neoplasia (CIN), and discusses the potential utility of fluorescence spectroscopy as a surrogate endpoint biomarker (SEB). The development and performance of a spectroscopic diagnostic algorithm for CIN is described in detail. Fluorescence excitation-emission matrices (EEMs) were obtained in vitro for 18 cervical biopsies from 10 patients. At all excitation emission maxima, but especially at 330 nm excitation, 385 nm emission, the average normalized fluorescence intensity of histologically normal tissue is greater than that of histologically abnormal tissue. A diagnostic algorithm based on the relative intensity at 330 nm excitation, 385 nm emission can differentiate histologically normal and abnormal biopsies with a higher sensitivity, but a lower positive predictive value and specificity than colposcopy. However, paired comparison of histologically normal and abnormal biopsies from the same patient results in a sensitivity of 75%, positive predictive value of 86%, and specificity of 88% for spectroscopic identification of histological abnormality--similar to that of colposcopy. Based on these results, in vivo studies of cervical tissue fluorescence were conducted. A spectroscopic system incorporating a pulsed nitrogen laser, an optical fiber probe, and an optical multi-channel analyzer was used to record fluorescence spectra of the intact cervix at colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)
Richards-Kortum, R; Mitchell, MF; Ramanujam, N; Mahadevan, A; Thomsen, S
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