Optical techniques for cervical neoplasia detection

Abstract

This paper provides an overview of the current research in the field of optical techniques for cervical neoplasia detection and covers a wide range of the existing and emerging technologies. Using colposcopy, a visual inspection of the uterine cervix with a colposcope (a binocular microscope with 3- to 15-fold magnification), has proven to be an efficient approach for the detection of invasive cancer. Nevertheless, the development of a reliable and cost-effective technique for the identification of precancerous lesions, confined to the epithelium (cervical intraepithelial neoplasia) still remains a challenging problem. It is known that even at early stages the neoplastic transformations of cervical tissue induce complex changes and modify both structural and biochemical properties of tissues. The different methods, including spectroscopic (diffuse reflectance spectroscopy, induced fluorescence and autofluorescence spectroscopy, Raman spectroscopy) and imaging techniques (confocal microscopy, optical coherence tomography, Mueller matrix imaging polarimetry, photoacoustic imaging), probe different tissue properties that may serve as optical biomarkers for diagnosis. Both the advantages and drawbacks of these techniques for the diagnosis of cervical precancerous lesions are discussed and compared.

Keywords: Mueller polarimetry; Raman spectroscopy; cervical intraepithelial neoplasia; confocal endomicroscopy; nanotheranostics; optical coherence tomography; optical spectroscopy.

Figure 1

Key steps for addressing cervical cancer as public health concern. New optical technologies and innovative approaches for the improvement of early detection of cervical pre-cancer (second step) are discussed in this paper.

Figure 2

Cross-section of uterus and vagina; schematics of cervical intraepithelial neoplasia development.

Figure 3

Cervical cancer estimated incidence, mortality and prevalence worldwide in 2012. Adapted from [22].

Figure 4

Diffuse reflectance and/or fluorescence spectroscopy for the optical analysis of tissue; λ is a wavelength. Adapted from [34].

Figure 5

Reflectance colposcopic images (a) before and (b) after application of acetic acid; (c) reconstructed histological map of lesions CIN 1, 2, and 3; (d) diagnostic map of disease probability provided by an automated multi-classifier. Reproduced with permission from [41], copyright 2008 Society of Photo-optical Instrumentation Engineers.

Figure 6

Site-to-site variations in fluorescence spectra measured at different pathologically confirmed (a) normal and (b) malignant tissue samples at 325 nm excitation wavelength. Reproduced with permission from [46], copyright 2006 Wiley-Liss, Inc.

Figure 7

Raman vibrational spectroscopy for probing the molecular chemical bonds as well as crystal lattice vibrations. ω_i is the frequency of the incident radiation.

Figure 8

Cervical epithelium examined using (i) colposcopy, (ii) confocal endomicroscopy and (iii) conventional histology (H&E staining). (a) Normal cervix; (b) cervical CIN 3 lesion. *Confocal image site. Scale bars = 100 µm. Reproduced with permission from [76], copyright 2006 Wiley-Liss, Inc.

Figure 9

Illustration of optical molecular-targeted imaging with nanoparticles.

Figure 10

Polarimetric images of a cervical specimen taken at 550 nm: (a) depolarization (b) scalar retardance and (c) azimuth of optical axis. The colored lines show the position of cuts and results of histological analysis (white: healthy squamous epithelium (H), violet: CIN 3, black: glandular epithelium (G)). Reproduced with permission from [105], copyright 2013 Optical Society of America.

Figure 11

(a) Histological map (colored lines) superimposed on an RGB image of a conization sample; HPV: epithelium infected by HPV; EO: external os of cervix; NI: non-identified epithelial zones, GE: glandular epithelium; SEM: squamous epithelium metaplasia; HSE: healthy squamous epithelium; CIN 1–3: squamous intraepithelial neoplasia of grade 1–3; (b) diagnostic (red: CIN 2–3, green: all other conditions) image segmentation using a threshold of 10.1° for the value of scalar retardance R for measurements performed at 450 nm; (c) receiver operating characteristic (ROC) curves (violet dashed: diagnostics based on scalar retardance values only, orange: diagnostics based on combination of scalar retardance and depolarization power values). Images adapted from [113], copyright 2016 Society of Photo-optical Instrumentation Engineers.

Figure 12

(a) OCT image of normal cervical tissue (BM: basement membrane, EP: epithelium, ST: stroma); (b) OCT image of a CIN 3 lesion; (c) OCT image of invasive carcinoma (length of white bar: 1 mm). Reproduced with permission from [131], copyright 2010 ISUOG.