SmartIHC-Analyzer: smartphone assisted microscopic image analytics for automated Ki-67 quantification in breast cancer evaluation

Abstract

As with other cancers, cell proliferation is one of the indicative hallmarks of breast cancer evaluation. The expression of human Ki-67, being a nuclear protein, has strong association with the proliferation of cancer cells. The proliferation index from Ki-67 is evaluated by immunohistochemical (IHC) study by discriminating positively (brown color) and negatively (blue color) stained nuclei of cells through manual counting. In practice, this evaluation process is highly dependent on an expert-pathologist, as well as being time consuming and prone to inter-observer variability. To circumvent current challenges in IHC image analysis, we introduce SmartIHC-Analyzer, an efficient smartphone assisted microscopy for automatic scoring of Ki-67 protein expression. A universal 3D printed adapter is fabricated to attach a smartphone to the eye-piece of the conventional microscope to acquire microscopic images of stained tissue slides. IHC image acquisition, analytics, visualization and automated reporting for Ki-67 have been developed and integrated in an android smartphone for easy use in any pathological set-up. Color deconvolution followed by morphological top-hat transformation and segmentation is performed to extract stained cells for automated scoring. The proposed SmartIHC-Analyzer app was tested on 30 cases of Ki-67 stained tissue samples and compared with the score given by expert pathologists with variability in illumination conditions. The results had high similarity with manual scoring by the expert pathologists (Pearson's correlation coefficient r = 0.97) and the average absolute variation from pathologists' score was evaluated as 6.21%; which is highly significant. The results have been compared with available state-of-the art ImmunoRatio software where the results are found to be promising. It can be highlighted that SmartIHC-Analyzer can be used in point-of-care diagnostics for instant automatic and augmented reporting of Ki-67 protein expression. The APK file of the SmartIHC-Analyzer is free to use and can be obtained by emailing the corresponding author.