Study of CuO Nanoparticle-induced Cell Death by High Content Cellular Fluorescence Imaging and Analysis

Xiaobo Zhou Jian Chen Jinmin Zhu Fuhai Li Xudong Huang Wong, S.T.C. Dept. of Radiol., Brigham & Women's Hosp., Boston, MA; This paper appears in: Circuits and Systems, 2007. ISCAS 2007. IEEE International Symposium on Publication Date: 27-30 May 2007 On page(s): 2878-2881 Location: New Orleans, LA, ISBN: 1-4244-0920-9 INSPEC Accession Number: 9539613 Digital Object Identifier: 10.1109/ISCAS.2007.378773 Current Version Published: 2007-06-25

Abstract To quantify cellular toxic responses to drug treatment or environmental stresses such as nanoparticles, a high throughput imaging modality with automated image analysis protocol is applied. Fluorescence images from human H4 neurogliomal cells exposed to different concentrations of CuO nanoparticles were collected by a high content fluorescence microscopy. A fully automated fluorescent cellular image analysis system has been developed for the consequential image analysis for cell viability. A data-driven background algorithm was used as adaptive multiple thresholding algorithm to categorize the cells into three classes: bright cells, dark cells, and background. Our image analysis approach includes: (1) the scale-space theory, namely Gaussian filtering with proper scale has been applied to the acquired images to generate local intensity maxima within each cell; (2) a novel method for defining local image intensity maxima based on the gradient vector field has been developed; and (3) a statistical model was proposed to overcome the problem of cell segmentation. Our data have shown that the automated image analysis protocol can achieve 90% success rate of cell detection compared to manual procedure. Cellular image analysis further indicated that H4 neuroglioma cells had a dose-dependent toxic response to the insult of CuO nanoparticles.

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