Digital colposcopy is a promising technology for the detection of cervical intraepithelial neoplasia. Automated analysis of colposcopic images could provide an inexpensive alternative to existing screening tools. Our goal is to develop a diagnostic tool that can automatically identify neoplastic tissue from digital images. A multispectral digital colposcope (MDC) is used to acquire reflectance images of the cervix with white light before and after acetic-acid application in 29 patients. A diagnostic image analysis tool is developed to identify neoplasia in the digital images. The digital image analysis is performed in two steps. First, similar optical patterns are clustered together. Second, classification algorithms are used to determine the probability that these regions contain neoplastic tissue. The classification results of each patient's images are assessed relative to the gold standard of histopathology. Acetic acid induces changes in the intensity of reflected light as well as the ratio of green to red reflected light. These changes are used to differentiate high-grade squamous intraepithelial (HGSIL) and cancerous lesions from normal or low-grade squamous intraepithelial (LGSIL) tissue. We report diagnostic performance with a sensitivity of 79% and a specificity of 88%. We show that diagnostically useful digital images of the cervix can be obtained using a simple and inexpensive device, and that automated image analysis algorithms show a potential to identify histologically neoplastic tissue areas.
An effective cancer control strategy requires improved early detection methods, patient-specific drug selection, and the ability to assess response to targeted therapeutics. Recently, plasmon resonance coupling between closely spaced metal nanoparticles has been used to develop ultrasensitive bioanalytical assays in vitro. We demonstrate the first in vivo application of plasmon coupling for molecular imaging of carcinogenesis. We describe molecular-specific gold bioconjugates to image epidermal growth factor receptor (EGFR); these conjugates can be delivered topically and imaged noninvasively in real time. We show that labeling with gold bioconjugates gives information on the overexpression and nanoscale spatial relationship of EGF receptors in cell membranes, both of which are altered in neoplasia. EGFR-mediated aggregation of gold nanoparticles in neoplastic cells results in more than a 100-nm color shift and a contrast ratio of more than tenfold in images of normal and precancerous epithelium in vivo, dramatically increasing contrast beyond values reported previously for antibody-targeted fluorescent dyes.
Measurement quality assurance plans for optical devices should be a mandatory part of grant funding submissions and
should explicitly affect scoring during review. These should include calibration strategy, standards selection strategy,
performance verification plan, performance validation plan and thorough preclinical performance validation. A
multispectral digital colposcope (MDC) has been designed to collect image data from patients as part of an NIH
sponsored clinical trial, based on a technology assessment model. Calibration strategy, standards selection and
performance verification methods are presented that may be used as a template for smaller groups or more limited
studies. With the MDC, red green and blue fluorescence images are captured under ultraviolet light excitation and red
and green images are captured under blue light excitation. Red, green and blue reflectance images are captured under
broadband white light illumination from a metal halide lamp in three modes - ordinary reflectance, and with polarized
illumination in combination with parallel and cross-polarized filtered imaging. The highly automated system was
designed to collect images of the cervix prior to and following the application of acetic acid. Three systems have been
built and will be operated in clinics in Vancouver, Canada, Houston, Texas and other locations in the developed and
developing world including Nigeria. The system is designed with a comprehensive set of calibration and performance
verification standards, based on our experience with large scale multi-center spectroscopy clinical trials and
measurements are made frequently prior to and following patient measurements. Automated performance verification
procedures are being designed based on measurements made during pilot studies to facilitate larger clinical trials.