A feasibility assessment of automated FISH image and signal analysis to assist cervical cancer detection

Abstract

Fluorescence in situ hybridization (FISH) technology provides a promising molecular imaging tool to detect cervical cancer. Since manual FISH analysis is difficult, time-consuming, and inconsistent, the automated FISH image scanning systems have been developed. Due to limited focal depth of scanned microscopic image, a FISH-probed specimen needs to be scanned in multiple layers that generate huge image data. To improve diagnostic efficiency of using automated FISH image analysis, we developed a computer-aided detection (CAD) scheme. In this experiment, four pap-smear specimen slides were scanned by a dual-detector fluorescence image scanning system that acquired two spectrum images simultaneously, which represent images of interphase cells and FISH-probed chromosome X. During image scanning, once detecting a cell signal, system captured nine image slides by automatically adjusting optical focus. Based on the sharpness index and maximum intensity measurement, cells and FISH signals distributed in 3-D space were projected into a 2-D con-focal image. CAD scheme was applied to each con-focal image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm and detect FISH-probed signals using a top-hat transform. The ratio of abnormal cells was calculated to detect positive cases. In four scanned specimen slides, CAD generated 1676 con-focal images that depicted analyzable cells. FISH-probed signals were independently detected by our CAD algorithm and an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots. The study demonstrated the feasibility of applying automated FISH image and signal analysis to assist cyto-geneticists in detecting cervical cancers.