title: Estimating real cell size distribution from cross-section microscopy imaging.
abstract: Microscopy imaging is an essential tool for medical diagnosis and molecular biology. It is particularly useful for extracting information about disease states, tissue heterogeneity and cell specific parameters such as cell type or cell size from biological specimens. However, the information obtained from the images is likely to be subjected to sampling and observational bias with respect to the underlying cell size/type distributions.
  
  
  
  We present an algorithm, Estimate Tissue Cell Size/Type Distribution (EstiTiCS), for the adjustment of the underestimation of the number of small cells and the size of measured cells while accounting for the section thickness independent of the tissue type. We introduce the sources of bias under different tissue distributions and their effect on the measured values with simulation experiments. Furthermore, we demonstrate our method on histological sections of paraffin-embedded adipose tissue sample images from 57 people from a dietary intervention study. This data consists of measured cell size and its distribution over the dietary intervention period at four time points. Adjusting for the bias with EstiTiCS results in a closer fit to the true/expected adipocyte size distribution with earlier studies. Therefore, we conclude that our method is suitable as the final step in estimating the tissue wide cell type/size distribution from microscopy imaging pipeline.
  
  
  
  Source code and its documentation are available at https://github.com/michaelLenz/EstiTiCS The whole pipeline of our method is implemented in R and makes use of the 'nloptr' package. Adipose tissue data used for this study are available on request.
  
  
  
  Michael.Lenz@Maastrichtuniversity.nl, Gokhan.Ertaylan@Maastrichtuniversity.nl.
authors: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors: Michael
authors: M
authors: Lenz
authors: Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors: Nadia J T
authors: NJ
authors: Roumans
authors: Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors: Roel G
authors: RG
authors: Vink
authors: Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors: Marleen A
authors: MA
authors: van Baak
authors: Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors: Edwin C M
authors: EC
authors: Mariman
authors: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors: Ilja C W
authors: IC
authors: Arts
authors: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors: Theo M
authors: TM
authors: de Kok
authors: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors: Gökhan
authors: G
authors: Ertaylan
mesh_terms: D000273:Adipose Tissue; D000465:Algorithms; D048429:Cell Size; D004032:Diet; D006801:Humans; D008853:Microscopy; D012984:Software