Near-infrared raman spectroscopy for early detection of cervical precancer

Abstract

This thesis work was centered on detecting cervical precancer using near-infrared (NIR) Raman spectroscopy. A rapid and portable NIR Raman spectroscopy system coupled with a specially designed ball lens fiber-optic Raman probe was successfully developed for in vivo tissue diagnosis and characterization. Firstly, Raman measurement was conducted on biopsied cervical tissues to test the feasibility of NIR Raman spectroscopy for the detection of cervical precancer. A good classification with an accuracy of 92.5% between benign and dysplasia (i.e., LGSILs and HGSILs) tissues was achieved ex vivo, encouraging the extension of our ex vivo work to in vivo study. Monte Carlo simulation method was employed to evaluate the performance (i.e., collection efficiency and depth-selectivity) of the ball lens fiber-optic Raman probe designs with various configurations (i.e., the diameter and refractive index of the ball lens). We demonstrated that the ball-lens NIR Raman spectroscopy developed is able to acquire good-quality Raman spectra of cervix in vivo. We demonstrated for the first time that NIR Raman spectroscopy in the high wavenumber (HW) region has the potential for the diagnosis of cervical precancer using our in-house developed Raman system and exhibits comparable diagnostic performance as Raman spectroscopy in fingerprint region. We also demonstrated that combining NIR autofluorescence and Raman spectroscopy can further improve the diagnosis of cervical precancer. We also evaluated the performance of ultraviolet/visible autofluorescence and diffuse reflectance spectroscopy in the characterization of cervical dysplasia and finally combined them with NIR Raman spectroscopy. It was found that optimal diagnosis of cervical precancer could be achieved by combining all these three different spectroscopic techniques together. The work completed in this thesis promotes some future directions to further optimize the diagnosis and detection of cervical precancer in vivo using Raman spectroscopy. One of the major directions is to develop robust software integrated with Raman spectral data preprocessing, statistical modeling for real-time in vivo tissue diagnosis and characterization. Another major direction is to develop fluorescence image-guided Raman spectroscopic diagnosis system to further facilitate and improve early diagnosis and detection of cervical precancer in clinical settings.