Low-Cost Chromatic Confocal Endomicroscope for the Diagnosis of Cervical Precancer

Abstract

Cervical cancer is one of the major cancers in women living in low- and middle-income countries (LMICs). The resources needed to conduct the gold standard histopathological diagnosis, such as a trained personnel and lab equipment, are scarce in LMICs. Hence, low-cost approaches such as visual inspection with acetic acid (VIA) are used to diagnose cervical cancer. VIA and other low-cost approaches, however, often lead to overdiagnosis and overtreatment of the patient due to their low specificity. There is an unmet need for a low-cost tool that can provide both high sensitivity and specificity.This dissertation discusses the design and development of a chromatic confocal endomicroscope (CCE) that can examine the cervical tissue in vivo with a goal of aiding the diagnosis of cervical malignancy. The novelty of this device is to use longitudinal chromatic aberration to acquire cross-sectional images of the tissue without any scanning mechanisms. A custom hyperchromatic objective lens was optimally designed to focus different wavelengths of the illumination light into different depths: 500-700 nm was focused over a depth range of 110 µm. Slit apertures were used for illumination and detection, which eliminated the need for beam scanning along the slit length direction and enabled cross-sectional, two-dimensional imaging without any mechanical scanners. A custom miniature spectrometer was used to analyze the spectrum of light scattered back from the tissue and generate confocal images. The manufactured CCE device had a small form factor with an overall device diameter and length of 9 mm and 70 mm, respectively. The material cost was less than $1,500. The measured lateral and axial resolution was 2 µm and 4 µm over an axial depth of 100 µm. The CCE device was able to visualize cellular structures of human tissue, in vivo at different axial depths. Cellular nuclei of the lower lip epithelium were clearly visualized from the CCE images, which might indicate that other epithelial tissues such as the cervical epithelium can also be visualized with CCE. This might merit clinical evaluation of CCE for the diagnosis of cervical malignancy.