Accurate Automatic Detection of Densely Distributed Cell Nuclei in 3D Space

PLoS Comput Biol. 2016 Jun 6;12(6):e1004970. doi: 10.1371/journal.pcbi.1004970. eCollection 2016 Jun.


To measure the activity of neurons using whole-brain activity imaging, precise detection of each neuron or its nucleus is required. In the head region of the nematode C. elegans, the neuronal cell bodies are distributed densely in three-dimensional (3D) space. However, no existing computational methods of image analysis can separate them with sufficient accuracy. Here we propose a highly accurate segmentation method based on the curvatures of the iso-intensity surfaces. To obtain accurate positions of nuclei, we also developed a new procedure for least squares fitting with a Gaussian mixture model. Combining these methods enables accurate detection of densely distributed cell nuclei in a 3D space. The proposed method was implemented as a graphical user interface program that allows visualization and correction of the results of automatic detection. Additionally, the proposed method was applied to time-lapse 3D calcium imaging data, and most of the nuclei in the images were successfully tracked and measured.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology
  • Cell Nucleus / physiology*
  • Computational Biology
  • Databases, Factual
  • Imaging, Three-Dimensional / methods*
  • Normal Distribution
  • Pattern Recognition, Automated / methods*

Associated data

  • figshare/10.6084/m9.figshare.3184546

Grant support

This work was supported by the CREST program “Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics” of the Japan Science and Technology Agency (JST). YI was supported by Grants-in-Aid for Innovative Areas “Systems molecular ethology” (20115002) and “Memory dynamism” (25115010), and "Comprehensive Brain Network" (221S0003). YT was supported by Grants-in-Aid for Young Scientists (B) (26830006) and for Research Activity start-up (24800014) and for Scientific Research on Innovative Areas (16H01418) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.