Among the many problems arising from cell biology and medicine, shape phenotype mapping (the detailed measurement of shape related quantities from cells and subcellular organelles) from microscopy images has received particular attention in the past due to its relevance to numerous biological processes.
We aim to make a fundamental contribution to cellular and subcellular phenotype mapping by developing methods for recover the underlying articulation parameters (deformation modes) of distribution of forms with particular relevance to cell biology. More specifically, we will couple a metric space formulation for biological forms with modern nonlinear manifold learning algorithms for characterizing (determination of mean shape, most likely modes of variation, statistical tests, etc.) shape distributions directly and automatically from image data. A particular innovative aspect of our work will be in allowing for using existing data to guide in the design of statistical tests to differentiate populations of cells (or subcellular organelles). These should allow for more sensitive statistical tests as compared with traditional approaches which are based on testing pre-conceived hypothesis. The methods we propose will be compared to already existing works in an effort to produce a standard, well-accepted technology. The successful completion of this project will have significant impact in areas such as pathology, high-throughput screening, cell motility studies, etc. by enabling one to perform many intricate tasks using a standard methodology.

Public Health Relevance

This research is aimed at supporting high-throughput shape phenotype mapping automatically from microscopic images through the introduction of a rigorous mathematical foundation, accompanied by suitable computational algorithms. More specifically, we will develop methodology for performing high-level shape measurements (determination of mean shape, most likely modes of variation, statistical tests, etc.) based on the spatial transformations that relate two or more forms as depicted in microscopy images. The methods we propose will be compared to already existing works in an effort to produce a standard, well-accepted technology. The successful completion of this project will have significant impact in areas such as pathology, high-throughput screening, cell motility studies, etc. by enabling one to perform many intricate tasks using a standard methodology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21GM088816-02
Application #
7945349
Study Section
Special Emphasis Panel (ZRG1-BST-K (02))
Program Officer
Deatherage, James F
Project Start
2009-09-30
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$184,994
Indirect Cost
Name
Carnegie-Mellon University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Huang, Hu; Tosun, Akif Burak; Guo, Jia et al. (2014) Cancer diagnosis by nuclear morphometry using spatial information (.) Pattern Recognit Lett 42:115-121
Ozolek, John A; Tosun, Akif Burak; Wang, Wei et al. (2014) Accurate diagnosis of thyroid follicular lesions from nuclear morphology using supervised learning. Med Image Anal 18:772-80
Wang, Wei; Slep?ev, Dejan; Basu, Saurav et al. (2013) A linear optimal transportation framework for quantifying and visualizing variations in sets of images. Int J Comput Vis 101:254-269
Chen, Cheng; Wang, Wei; Ozolek, John A et al. (2013) A flexible and robust approach for segmenting cell nuclei from 2D microscopy images using supervised learning and template matching. Cytometry A 83:495-507
Rohde, Gustavo Kunde (2013) New methods for quantifying and visualizing information from images of cells: An overview. Conf Proc IEEE Eng Med Biol Soc 2013:121-4
Buck, Taráz E; Li, Jieyue; Rohde, Gustavo K et al. (2012) Toward the virtual cell: automated approaches to building models of subcellular organization ""learned"" from microscopy images. Bioessays 34:791-9
Choi, Siwon; Wang, Wei; Ribeiro, Alexandrew J S et al. (2011) Computational image analysis of nuclear morphology associated with various nuclear-specific aging disorders. Nucleus 2:570-9
Wang, Wei; Mo, Yilin; Ozolek, John A et al. (2011) Penalized Fisher Discriminant Analysis and Its Application to Image-Based Morphometry. Pattern Recognit Lett 32:2128-2135
Wang, Wei; Ozolek, John A; Slepcev, Dejan et al. (2011) An optimal transportation approach for nuclear structure-based pathology. IEEE Trans Med Imaging 30:621-31
Wang, Wei; Ozolek, John A; Rohde, Gustavo K (2010) Detection and classification of thyroid follicular lesions based on nuclear structure from histopathology images. Cytometry A 77:485-94